Trial Outcomes & Findings for Exercise Therapy to Reduce Heart Failure Symptoms; Sorting Mechanisms of Benefit (NCT NCT03648762)

NCT ID: NCT03648762

Last Updated: 2024-06-24

Results Overview

a cardiopulmonary exercise test will be performed to determined peak VO2 in ML/KG/Min

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 65 participants
• Primary outcome timeframe: baseline and through study completion an average of 14 weeks
• Results posted on: 2024-06-24

Participant Flow

65 participants consented to enroll in the study. 45 participants completed a baseline assessment and were randomized to one of the three intervention arms. The remaining 20 participants withdrew prior to completing baseline and before being randomized to one of the three intervention arms, so they are not included in this table. Serious adverse events reported after consent but prior to withdrawal for the non-randomized participants are included in a separate group in the adverse events table.

Participant milestones

Measure	Aerobic Exercise Intervention Participants completed a 12-week exercise training regimen consisting of aerobic exercise for a minimum of 60 minutes in length three times a week.	Combined Aerobic and Strength Exercise Intervention Participants completed a 12-week exercise training regimen consisting of combined aerobic and strength exercise for a minimum of 60 minutes in length three times a week.	Inspiratory Muscle Training Exercise Intervention Participants completed a 12-week exercise training regimen consisting of inspiratory muscle training exercise for a minimum of 60 minutes in length three times a week.
Overall Study STARTED	16	17	12
Overall Study COMPLETED	10	13	11
Overall Study NOT COMPLETED	6	4	1

Reasons for withdrawal

Measure	Aerobic Exercise Intervention Participants completed a 12-week exercise training regimen consisting of aerobic exercise for a minimum of 60 minutes in length three times a week.	Combined Aerobic and Strength Exercise Intervention Participants completed a 12-week exercise training regimen consisting of combined aerobic and strength exercise for a minimum of 60 minutes in length three times a week.	Inspiratory Muscle Training Exercise Intervention Participants completed a 12-week exercise training regimen consisting of inspiratory muscle training exercise for a minimum of 60 minutes in length three times a week.
Overall Study Lost to Follow-up	1	2	0
Overall Study Withdrawal by Subject	5	2	1

Baseline Characteristics

Exercise Therapy to Reduce Heart Failure Symptoms; Sorting Mechanisms of Benefit

Baseline characteristics by cohort

Measure	Aerobic Exercise Intervention n=16 Participants Participants completed a 12-week exercise training regimen consisting of aerobic exercise for a minimum of 60 minutes in length three times a week.	Combined Aerobic and Strength Exercise Intervention n=13 Participants Participants completed a 12-week exercise training regimen consisting of combined aerobic and strength exercise for a minimum of 60 minutes in length three times a week.	Inspiratory Muscle Training Exercise Intervention n=12 Participants Participants completed a 12-week exercise training regimen consisting of inspiratory muscle training exercise for a minimum of 60 minutes in length three times a week.	Consented But Withdrew Pre-randomization n=7 Participants This group includes participants who consented to enroll in the study, but only completed partial or no baseline functional or questionnaire assessments, and then withdrew from the study prior to being randomized. Therefore these participants were not randomly assigned to one of the three study arms, but baseline demographic data were collected after consent and prior to randomization. The baseline demographic data are included here for completion.	Total n=48 Participants Total of all reporting groups
Age, Continuous	70.1 years STANDARD_DEVIATION 7.5 • n=5 Participants	67.6 years STANDARD_DEVIATION 7.9 • n=7 Participants	69.2 years STANDARD_DEVIATION 5.0 • n=5 Participants	70.7 years STANDARD_DEVIATION 9.8 • n=4 Participants	69.7 years STANDARD_DEVIATION 7.7 • n=21 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	13 Participants n=7 Participants	12 Participants n=5 Participants	7 Participants n=4 Participants	48 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	9 Participants n=21 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	10 Participants n=7 Participants	10 Participants n=5 Participants	1 Participants n=4 Participants	28 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	6 Participants n=4 Participants	11 Participants n=21 Participants

PRIMARY outcome

Timeframe: baseline and through study completion an average of 14 weeks

Population: Pre and post peak VO2 data available for 33 of 45 randomized participants. Remaining randomized participants did not complete a post assessment so are excluded from the table.

a cardiopulmonary exercise test will be performed to determined peak VO2 in ML/KG/Min

Outcome measures

Measure	Aerobic Exercise Intervention n=10 Participants Participants completed a 12-week exercise training regimen consisting of aerobic exercise for a minimum of 60 minutes in length three times a week.	Combined Aerobic and Strength Exercise Intervention n=12 Participants Participants completed a 12-week exercise training regimen consisting of combined aerobic and strength exercise for a minimum of 60 minutes in length three times a week.	Inspiratory Muscle Training Exercise Intervention n=11 Participants Participants completed a 12-week exercise training regimen consisting of inspiratory muscle training exercise for a minimum of 60 minutes in length three times a week.
Oxygen Uptake (VO2) Peak Baseline	1778.1 ML/KG/Min Standard Deviation 679.1	1228.2 ML/KG/Min Standard Deviation 519.4	1393.7 ML/KG/Min Standard Deviation 305.3
Oxygen Uptake (VO2) Peak Follow-up	1763.6 ML/KG/Min Standard Deviation 736.6	1295.4 ML/KG/Min Standard Deviation 499.4	1405.9 ML/KG/Min Standard Deviation 370.7

PRIMARY outcome

Timeframe: baseline and through study completion an average of 14 weeks

Population: Data available for 30 of 45 randomized participants who completed both a pre and post assessment.

Leg press will be performed on the Keiser Leg press and measured in kilograms (kg)

Outcome measures

Measure	Aerobic Exercise Intervention n=10 Participants Participants completed a 12-week exercise training regimen consisting of aerobic exercise for a minimum of 60 minutes in length three times a week.	Combined Aerobic and Strength Exercise Intervention n=11 Participants Participants completed a 12-week exercise training regimen consisting of combined aerobic and strength exercise for a minimum of 60 minutes in length three times a week.	Inspiratory Muscle Training Exercise Intervention n=9 Participants Participants completed a 12-week exercise training regimen consisting of inspiratory muscle training exercise for a minimum of 60 minutes in length three times a week.
One Repetition Maximum- Leg Press 1 Rep Max Leg press follow-up	433 kg Standard Deviation 232.7	355.5 kg Standard Deviation 160.3	409.5 kg Standard Deviation 136.4
One Repetition Maximum- Leg Press 1 Rep Max Leg press baseline	430.3 kg Standard Deviation 208.6	348.2 kg Standard Deviation 143.0	421.1 kg Standard Deviation 100.1

SECONDARY outcome

Timeframe: baseline and through study completion an average of 14 weeks

Population: Nitric oxide bioavailability metabolomics data were collected for 23 of the participants at both the baseline and follow-up assessments.

Nitric Oxide Bioavailability (uM) Metabolomics

The scientific direction of our analyses for this measure has shifted over time. The investigators will pursue RNA seq and metabolomics to provide an unbiased path forward on viable targets in the muscle.

Outcome measures

Measure	Aerobic Exercise Intervention n=5 Participants Participants completed a 12-week exercise training regimen consisting of aerobic exercise for a minimum of 60 minutes in length three times a week.	Combined Aerobic and Strength Exercise Intervention n=9 Participants Participants completed a 12-week exercise training regimen consisting of combined aerobic and strength exercise for a minimum of 60 minutes in length three times a week.	Inspiratory Muscle Training Exercise Intervention n=9 Participants Participants completed a 12-week exercise training regimen consisting of inspiratory muscle training exercise for a minimum of 60 minutes in length three times a week.
Metabolomics Baseline Nitric Oxide (uM)	6.2 micrometer (uM) Standard Deviation 3.7	7.7 micrometer (uM) Standard Deviation 2.5	7.2 micrometer (uM) Standard Deviation 3.5
Metabolomics Follow-up Nitric Oxide (uM)	5.6 micrometer (uM) Standard Deviation 2.4	10.8 micrometer (uM) Standard Deviation 8.9	6.6 micrometer (uM) Standard Deviation 3.1

SECONDARY outcome

Timeframe: baseline and through study completion an average of 14 weeks

Population: Skeletal muscle samples were collected for 19 participants who completed both a baseline and follow-up assessment.

Skeletal muscle gene expression will be measured in RNA isolated from skeletal muscle biopsy samples via Illumina platform.

The measure "Number" indicates the number of differentially expressed genes, and units are fold change over baseline. To investigate how the lifestyle interventions impacted gene expression at the mRNA level in skeletal muscles of our research participants we performed high-throughput RNA-Sequencing (Illumina HiSeq paired-end 150 base pairs). Differential gene expression analysis was performed on the RNA-seq. data using DeSEQ2 to determine differentially expressed genes (DEGs) between groups. All DEG analyses were performed using the Wald test (p < 0.05) corrected for multiple comparisons using the Benjamini and Hochberg method.

Outcome measures

Measure	Aerobic Exercise Intervention n=4 Participants Participants completed a 12-week exercise training regimen consisting of aerobic exercise for a minimum of 60 minutes in length three times a week.	Combined Aerobic and Strength Exercise Intervention n=7 Participants Participants completed a 12-week exercise training regimen consisting of combined aerobic and strength exercise for a minimum of 60 minutes in length three times a week.	Inspiratory Muscle Training Exercise Intervention n=8 Participants Participants completed a 12-week exercise training regimen consisting of inspiratory muscle training exercise for a minimum of 60 minutes in length three times a week.
Skeletal Muscle Gene Expression	0 Fold change over baseline	1 Fold change over baseline	1 Fold change over baseline

SECONDARY outcome

Timeframe: baseline and through study completion an average of 12 weeks

Population: Questionnaire data available for 32 participants who completed both the baseline and 12-week follow-up assessments.

Participants completed the Kansas City Cardiomyopathy questionnaire (KCCQ) and Duke Activity Status (DASI) Index standardized questionnaires.

The KCCQ is scored on a scale of 0 to 100 with a higher score representing better health status.

DASI is a 12-item questionnaire that is scored on a scale of 0 to 58.2, with a higher score representing a higher functional status.

Outcome measures

Measure	Aerobic Exercise Intervention n=10 Participants Participants completed a 12-week exercise training regimen consisting of aerobic exercise for a minimum of 60 minutes in length three times a week.	Combined Aerobic and Strength Exercise Intervention n=12 Participants Participants completed a 12-week exercise training regimen consisting of combined aerobic and strength exercise for a minimum of 60 minutes in length three times a week.	Inspiratory Muscle Training Exercise Intervention n=10 Participants Participants completed a 12-week exercise training regimen consisting of inspiratory muscle training exercise for a minimum of 60 minutes in length three times a week.
Quality of Life and Daily Function Questionnaires KCCQ Baseline Score	36 scores on a scale Standard Deviation 10.6	37.7 scores on a scale Standard Deviation 12.0	39.5 scores on a scale Standard Deviation 16.2
Quality of Life and Daily Function Questionnaires KCCQ Follow-up Score	40 scores on a scale Standard Deviation 14.0	38 scores on a scale Standard Deviation 13.2	43 scores on a scale Standard Deviation 19.1
Quality of Life and Daily Function Questionnaires DASI Baseline Overall Score	37.3 scores on a scale Standard Deviation 14.6	34.7 scores on a scale Standard Deviation 15.4	33.4 scores on a scale Standard Deviation 12.2
Quality of Life and Daily Function Questionnaires DASI Follow-up Overall Score	37.3 scores on a scale Standard Deviation 15.2	32.9 scores on a scale Standard Deviation 13.0	33.4 scores on a scale Standard Deviation 15.9

SECONDARY outcome

Timeframe: baseline and through study completion an average of 12 weeks

Population: Questionnaire data available for 32 participants who completed both the baseline and 12-week follow-up assessments. The mean at baseline and 12-week follow-up are reported.

Participants completed the Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults as part of the Quality of Life and Daily Function study outcome.

The CHAMPS questionnaire assesses duration and frequency of self-reported weekly physical activities of varying intensities in older adults.

One component of the CHAMPS score is the frequency per week (i.e. number or count of events per week) that the participant reported that they engaged in all exercise related activities, and the frequency per week that the participant engaged in moderate-vigorous activities.

The mean frequency of activities per week at baseline and follow-up for each study arm are reported here for the participants who completed both a baseline and follow-up assessment. A higher mean indicates a higher number of exercise-related activities were reported per week.

Outcome measures

Measure	Aerobic Exercise Intervention n=10 Participants Participants completed a 12-week exercise training regimen consisting of aerobic exercise for a minimum of 60 minutes in length three times a week.	Combined Aerobic and Strength Exercise Intervention n=12 Participants Participants completed a 12-week exercise training regimen consisting of combined aerobic and strength exercise for a minimum of 60 minutes in length three times a week.	Inspiratory Muscle Training Exercise Intervention n=10 Participants Participants completed a 12-week exercise training regimen consisting of inspiratory muscle training exercise for a minimum of 60 minutes in length three times a week.
Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Frequency Component Baseline Mean Frequency of all Physical Activity bouts per week (CHAMPS)	14.7 events per week Standard Deviation 9.2	13.6 events per week Standard Deviation 9.3	9.5 events per week Standard Deviation 4.2
Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Frequency Component Follow-up Mean Frequency of all Physical Activity bouts per week (CHAMPS)	23.5 events per week Standard Deviation 10.9	22.5 events per week Standard Deviation 11.8	19.5 events per week Standard Deviation 9.1
Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Frequency Component Baseline Mean Frequency of Moderate-Vigorous Physical Activity bouts per week (CHAMPS)	5.5 events per week Standard Deviation 5.6	6.3 events per week Standard Deviation 4.9	3.0 events per week Standard Deviation 2.9
Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Frequency Component Follow-up Mean Frequency of Moderate-Vigorous Physical Activity bouts per week (CHAMPS)	12.1 events per week Standard Deviation 8.1	10.6 events per week Standard Deviation 6.7	7.7 events per week Standard Deviation 4.9

SECONDARY outcome

Timeframe: baseline and through study completion an average of 12 weeks

Population: Questionnaire data available for 32 participants who completed both the baseline and 12-week follow-up assessments. The mean at baseline and 12-week follow-up are reported.

Participants completed the Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults as part of the Quality of Life and Daily Function study outcome.

The CHAMPS questionnaire assesses duration and frequency of self-reported weekly physical activities of varying intensities in older adults.

One component of the CHAMPS score is the self-reported duration in hours per week of all exercise-related activities, and duration in hours per week of moderate-vigorous exercise-related activities.

The mean duration of all exercise-related activities and moderate-vigorous activities in hours per week are reported here for participants in each study arm who completed both the baseline and 12 week follow-up assessments. A higher mean indicates that a longer duration of exercise-related activities in hours per week were reported.

Outcome measures

Measure	Aerobic Exercise Intervention n=10 Participants Participants completed a 12-week exercise training regimen consisting of aerobic exercise for a minimum of 60 minutes in length three times a week.	Combined Aerobic and Strength Exercise Intervention n=12 Participants Participants completed a 12-week exercise training regimen consisting of combined aerobic and strength exercise for a minimum of 60 minutes in length three times a week.	Inspiratory Muscle Training Exercise Intervention n=10 Participants Participants completed a 12-week exercise training regimen consisting of inspiratory muscle training exercise for a minimum of 60 minutes in length three times a week.
Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Duration Component Baseline Mean Duration of all Physical Activity bouts (CHAMPS)	15.2 hours per week Standard Deviation 8.1	7.7 hours per week Standard Deviation 4.5	5.7 hours per week Standard Deviation 3.2
Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Duration Component Follow-up Mean Duration of all Physical Activity bouts (CHAMPS)	21.8 hours per week Standard Deviation 15.9	14.3 hours per week Standard Deviation 8.6	14.4 hours per week Standard Deviation 9.6
Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Duration Component Baseline Mean Duration of Moderate-Vigorous Physical Activity bouts (CHAMPS)	6.8 hours per week Standard Deviation 8.5	3.5 hours per week Standard Deviation 2.7	1.8 hours per week Standard Deviation 1.9
Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Duration Component Follow-up Mean Duration of Moderate-Vigorous Physical Activity bouts (CHAMPS)	11.6 hours per week Standard Deviation 11.7	7.4 hours per week Standard Deviation 6.2	5.5 hours per week Standard Deviation 5.4

OTHER_PRE_SPECIFIED outcome

Timeframe: baseline and through study completion an average of 14 weeks

Population: Data for the C-reactive protein outcome was collected for 28 participants.

Inflammation - C-reactive protein (CRP) will be measured through blood

Outcome measures

Measure	Aerobic Exercise Intervention n=8 Participants Participants completed a 12-week exercise training regimen consisting of aerobic exercise for a minimum of 60 minutes in length three times a week.	Combined Aerobic and Strength Exercise Intervention n=9 Participants Participants completed a 12-week exercise training regimen consisting of combined aerobic and strength exercise for a minimum of 60 minutes in length three times a week.	Inspiratory Muscle Training Exercise Intervention n=11 Participants Participants completed a 12-week exercise training regimen consisting of inspiratory muscle training exercise for a minimum of 60 minutes in length three times a week.
Inflammation - C-reactive Protein Follow-up CRP (mg/L)	4.1 mg/L Standard Deviation 4.1	4.2 mg/L Standard Deviation 3.4	2.1 mg/L Standard Deviation 2.1
Inflammation - C-reactive Protein Baseline CRP (mg/L)	3.3 mg/L Standard Deviation 1.5	3.8 mg/L Standard Deviation 2.5	1.8 mg/L Standard Deviation 1.6

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and through study completion an average of 14 weeks

Population: 23 randomized participants completed baseline dual-energy x-ray absorptiometry, and 15 of those completed the follow-up scan.

dual-energy x-ray absorptiometry will look at muscle mass change in kg

Outcome measures

Measure	Aerobic Exercise Intervention n=4 Participants Participants completed a 12-week exercise training regimen consisting of aerobic exercise for a minimum of 60 minutes in length three times a week.	Combined Aerobic and Strength Exercise Intervention n=11 Participants Participants completed a 12-week exercise training regimen consisting of combined aerobic and strength exercise for a minimum of 60 minutes in length three times a week.	Inspiratory Muscle Training Exercise Intervention n=8 Participants Participants completed a 12-week exercise training regimen consisting of inspiratory muscle training exercise for a minimum of 60 minutes in length three times a week.
Dual-energy X-ray Absorptiometry Appendicular Lean Mass Baseline	3.96 kg Standard Deviation 1.14	3.08 kg Standard Deviation 0.45	3.08 kg Standard Deviation 0.49
Dual-energy X-ray Absorptiometry Appendicular Lean Mass Follow-up	8.73 kg Standard Deviation 1.29	7.74 kg Standard Deviation 1.28	7.72 kg Standard Deviation 0.99

Adverse Events

Aerobic Exercise Intervention

Serious events: 10 serious events

Other events: 0 other events

Deaths: 0 deaths

Combined Aerobic and Strength Exercise Intervention

Serious events: 3 serious events

Other events: 0 other events

Deaths: 0 deaths

Inspiratory Muscle Training Exercise Intervention

Serious events: 5 serious events

Other events: 1 other events

Deaths: 0 deaths

Consented But Withdrew Pre-randomization

Serious events: 5 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Aerobic Exercise Intervention n=16 participants at risk Participants completed a 12-week exercise training regimen consisting of aerobic exercise for a minimum of 60 minutes in length three times a week.	Combined Aerobic and Strength Exercise Intervention n=17 participants at risk Participants completed a 12-week exercise training regimen consisting of combined aerobic and strength exercise for a minimum of 60 minutes in length three times a week.	Inspiratory Muscle Training Exercise Intervention n=12 participants at risk Participants completed a 12-week exercise training regimen consisting of inspiratory muscle training exercise for a minimum of 60 minutes in length three times a week.	Consented But Withdrew Pre-randomization n=5 participants at risk Participants who consented to enroll in the study, but only completed partial or no baseline assessments and then withdrew from the study prior to being randomized. These participants were not assigned to one of the three study arms, but had adverse event data that was reported after their consent and prior to withdrawal.
Infections and infestations Influenza	6.2% 1/16 • Number of events 1 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/17 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/12 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/5 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.
Musculoskeletal and connective tissue disorders Gout	0.00% 0/16 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/17 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	8.3% 1/12 • Number of events 1 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/5 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.
Musculoskeletal and connective tissue disorders Chest wall pain	6.2% 1/16 • Number of events 1 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/17 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/12 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/5 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.
Surgical and medical procedures Eye Surgery	6.2% 1/16 • Number of events 1 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/17 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/12 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/5 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.
Musculoskeletal and connective tissue disorders Shoulder fracture	6.2% 1/16 • Number of events 1 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/17 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/12 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/5 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/16 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/17 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/12 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/5 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.
Musculoskeletal and connective tissue disorders Mechanical Fall with Fractures	0.00% 0/16 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/17 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/12 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	20.0% 1/5 • Number of events 1 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.
Cardiac disorders Acute Heart Failure	6.2% 1/16 • Number of events 2 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/17 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/12 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/5 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.
General disorders Feeling faint	6.2% 1/16 • Number of events 1 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/17 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/12 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/5 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.
Cardiac disorders Hypertension	0.00% 0/16 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/17 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/12 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	20.0% 1/5 • Number of events 1 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.
Cardiac disorders LV thrombus	6.2% 1/16 • Number of events 1 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/17 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/12 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/5 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.
General disorders Stomach, Chest pain	0.00% 0/16 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	5.9% 1/17 • Number of events 1 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/12 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/5 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.
Musculoskeletal and connective tissue disorders Shoulder pain after fall on ice	0.00% 0/16 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/17 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	8.3% 1/12 • Number of events 1 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/5 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.
Cardiac disorders Chest Pain	0.00% 0/16 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/17 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	8.3% 1/12 • Number of events 1 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/5 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.
General disorders dizziness, SOB, fogginess after medication change	0.00% 0/16 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/17 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	8.3% 1/12 • Number of events 1 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/5 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.
Respiratory, thoracic and mediastinal disorders Unknown Respiratory Disorder	6.2% 1/16 • Number of events 1 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/17 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/12 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	20.0% 1/5 • Number of events 1 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.
Cardiac disorders Hypotension	0.00% 0/16 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/17 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/12 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	20.0% 1/5 • Number of events 1 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.
Musculoskeletal and connective tissue disorders Mechanical fall on head	6.2% 1/16 • Number of events 1 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/17 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/12 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/5 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.
Endocrine disorders Hypoglycemia	0.00% 0/16 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	5.9% 1/17 • Number of events 1 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/12 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/5 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.
Gastrointestinal disorders Constipation	0.00% 0/16 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	5.9% 1/17 • Number of events 1 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/12 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/5 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.
Skin and subcutaneous tissue disorders Thigh skin flap removal	0.00% 0/16 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/17 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/12 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	20.0% 1/5 • Number of events 1 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.
General disorders Lightheadedness after starting new medication	0.00% 0/16 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/17 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	8.3% 1/12 • Number of events 1 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/5 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.
Cardiac disorders Atrial fibrillation	6.2% 1/16 • Number of events 1 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/17 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/12 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/5 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.
General disorders Edema	6.2% 1/16 • Number of events 1 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/17 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/12 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/5 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.

Other adverse events

Measure	Aerobic Exercise Intervention n=16 participants at risk Participants completed a 12-week exercise training regimen consisting of aerobic exercise for a minimum of 60 minutes in length three times a week.	Combined Aerobic and Strength Exercise Intervention n=17 participants at risk Participants completed a 12-week exercise training regimen consisting of combined aerobic and strength exercise for a minimum of 60 minutes in length three times a week.	Inspiratory Muscle Training Exercise Intervention n=12 participants at risk Participants completed a 12-week exercise training regimen consisting of inspiratory muscle training exercise for a minimum of 60 minutes in length three times a week.	Consented But Withdrew Pre-randomization n=5 participants at risk Participants who consented to enroll in the study, but only completed partial or no baseline assessments and then withdrew from the study prior to being randomized. These participants were not assigned to one of the three study arms, but had adverse event data that was reported after their consent and prior to withdrawal.
Musculoskeletal and connective tissue disorders Spinal stenosis	0.00% 0/16 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/17 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	8.3% 1/12 • Number of events 1 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.	0.00% 0/5 • After consent through study completion, up to 12 weeks Serious Adverse Events (SAEs) were reported for participants who consented to the study and were therefore considered enrolled. Some participants experienced an adverse event after consent but prior to completing the full baseline assessments, and withdrew from the study before they were randomized to one of the three intervention arms. For completion, the SAEs reported for these participants are listed in a separate "consented but withdrew pre-randomization" column.

Additional Information

Daniel E. Forman, MD

VA Pittsburgh Healthcare System

Phone: (412) 360-2917

Email: Daniel.Forman@va.gov

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place