Trial Outcomes & Findings for Exercise, Brain, and Cardiovascular Health (NCT NCT03841669)

Results Overview

Magnetic Resonance Imaging (MRI) will be used to measure the structure of the brain. Segmentation algorithms applied to structural MRI images will be used to compute the volume of the hippocampus in particular, which will be evaluated for change over the course of the trial.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

130 participants

Primary outcome timeframe

Baseline & 12 months

Results posted on

2025-02-24

Participant Flow

Participant milestones

Participant milestones
Measure	Aerobic Exercise Group This is the experimental group. Exercise is prescribed for 150 min/week. Due to COVID-19 restrictions the exercise supervision was allowed to be either remotely or in the context of a laboratory setting. Aerobic Exercise Group: Guidelines for exercise programming (ACSM, 2018) will be followed including a warm up and cool down, progressive and gradual increments in duration, and instruction regarding avoidance of physical activity related injury. The exercise group will receive moderate to vigorous intensity aerobic exercise targeting 150 minutes per week for 12 months. The group will target dividing these minutes into 3 exercise sessions a week. The prescribed intensity will be based on their maximal fitness testing heart rate and then calculated per a research grade method. They will maintain a minimum heart rate from their specific calculation that will be monitored by Polar Heart Rate straps.	Physical Activity & Health Information Group This is the control group. Participants will engage in daily life monitoring every 6 weeks. Physical Activity \& Health Information Group: This group will not partake in the aerobic fitness sessions but will be asked to wear a daily monitoring device every 6 weeks. They will also complete all baseline, 6-month (optional), and 12-month visits.
Overall Study STARTED	64	66
Overall Study COMPLETED	41	41
Overall Study NOT COMPLETED	23	25

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Exercise, Brain, and Cardiovascular Health

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Aerobic Exercise Group n=64 Participants This is the experimental group. Exercise is prescribed for 150 min/week. Due to COVID-19 restrictions the exercise supervision was allowed to be either remotely or in the context of a laboratory setting. Aerobic Exercise Group: Guidelines for exercise programming (ACSM, 2018) will be followed including a warm up and cool down, progressive and gradual increments in duration, and instruction regarding avoidance of physical activity related injury. The exercise group will receive moderate to vigorous intensity aerobic exercise targeting 150 minutes per week for 12 months. The group will target dividing these minutes into 3 exercise sessions a week. The prescribed intensity will be based on their maximal fitness testing heart rate and then calculated per a research grade method. They will maintain a minimum heart rate from their specific calculation that will be monitored by Polar Heart Rate straps.	Physical Activity & Health Information Group n=66 Participants This is the control group. Participants will engage in daily life monitoring every 6 weeks. Physical Activity \& Health Information Group: This group will not partake in the aerobic fitness sessions but will be asked to wear a daily monitoring device every 6 weeks. They will also complete all baseline, 6-month (optional), and 12-month visits.	Total n=130 Participants Total of all reporting groups
Age, Continuous	41.55 years STANDARD_DEVIATION 10.48 • n=5 Participants	40.98 years STANDARD_DEVIATION 9.40 • n=7 Participants	41.26 years STANDARD_DEVIATION 9.91 • n=5 Participants
Sex: Female, Male Female	43 Participants n=5 Participants	45 Participants n=7 Participants	88 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants	21 Participants n=7 Participants	42 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	59 Participants n=5 Participants	64 Participants n=7 Participants	123 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants	9 Participants n=7 Participants	14 Participants n=5 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
Race (NIH/OMB) Black or African American	11 Participants n=5 Participants	5 Participants n=7 Participants	16 Participants n=5 Participants
Race (NIH/OMB) White	42 Participants n=5 Participants	49 Participants n=7 Participants	91 Participants n=5 Participants
Race (NIH/OMB) More than one race	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
VO2peak	26.85 mL/kg/min STANDARD_DEVIATION 6.60 • n=5 Participants	30.23 mL/kg/min STANDARD_DEVIATION 6.93 • n=7 Participants	28.57 mL/kg/min STANDARD_DEVIATION 6.95 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline & 12 months

Population: All randomized participants were included in intention-to-treat (ITT) analyses.

Magnetic Resonance Imaging (MRI) will be used to measure the structure of the brain. Segmentation algorithms applied to structural MRI images will be used to compute the volume of the hippocampus in particular, which will be evaluated for change over the course of the trial.

Outcome measures

Outcome measures
Measure	Aerobic Exercise Group n=64 Participants This is the experimental group. Exercise is prescribed for 150 min/week. Due to COVID-19 restrictions the exercise supervision was allowed to be either remotely or in the context of a laboratory setting. Aerobic Exercise Group: Guidelines for exercise programming (ACSM, 2018) will be followed including a warm up and cool down, progressive and gradual increments in duration, and instruction regarding avoidance of physical activity related injury. The exercise group will receive moderate to vigorous intensity aerobic exercise targeting 150 minutes per week for 12 months. The group will target dividing these minutes into 3 exercise sessions a week. The prescribed intensity will be based on their maximal fitness testing heart rate and then calculated per a research grade method. They will maintain a minimum heart rate from their specific calculation that will be monitored by Polar Heart Rate straps.	Physical Activity & Health Information Group n=66 Participants This is the control group. Participants will engage in daily life monitoring every 6 weeks. Physical Activity \& Health Information Group: This group will not partake in the aerobic fitness sessions but will be asked to wear a daily monitoring device every 6 weeks. They will also complete all baseline, 6-month (optional), and 12-month visits.
Change in Hippocampal Volume	-15.4 mm^3 Interval -79.3 to 48.4	-49.9 mm^3 Interval -112.8 to 13.0

SECONDARY outcome

Timeframe: Baseline & 12 months

Population: Randomized participants who had baseline systolic blood pressure measures available were included in intention-to-treat (ITT) analyses.

Average systolic blood pressure will be computed during a resting baseline period and during the performance of two behavioral tasks, (1) a Stroop color-word interference task and (2) a multi-source interference task. Mean baseline levels of systolic blood pressure will be subtracted from mean levels averaged across the two tasks to compute response scores, and changes in task-response scores will be evaluated over the course of the trial.

Outcome measures

Outcome measures
Measure	Aerobic Exercise Group n=55 Participants This is the experimental group. Exercise is prescribed for 150 min/week. Due to COVID-19 restrictions the exercise supervision was allowed to be either remotely or in the context of a laboratory setting. Aerobic Exercise Group: Guidelines for exercise programming (ACSM, 2018) will be followed including a warm up and cool down, progressive and gradual increments in duration, and instruction regarding avoidance of physical activity related injury. The exercise group will receive moderate to vigorous intensity aerobic exercise targeting 150 minutes per week for 12 months. The group will target dividing these minutes into 3 exercise sessions a week. The prescribed intensity will be based on their maximal fitness testing heart rate and then calculated per a research grade method. They will maintain a minimum heart rate from their specific calculation that will be monitored by Polar Heart Rate straps.	Physical Activity & Health Information Group n=62 Participants This is the control group. Participants will engage in daily life monitoring every 6 weeks. Physical Activity \& Health Information Group: This group will not partake in the aerobic fitness sessions but will be asked to wear a daily monitoring device every 6 weeks. They will also complete all baseline, 6-month (optional), and 12-month visits.
Change in Systolic Blood Pressure Responses to Behavioral Tasks	-0.932 mmHg Interval -3.7 to 1.836	-3.519 mmHg Interval -6.2 to -0.835

SECONDARY outcome

Timeframe: Baseline & 12 months

Population: Randomized participants who had heart rate variability measures available at baseline were included in intention-to-treat (ITT) analyses.

Heart rate variability will be computed from inter-beat intervals derived from electrocardiographic recordings while participants rest in the seated position. Average heart rate variability values from the recording period will be assessed for their change over the trial. Here, we report the natural log-transformed variance of high-frequency (HF) heart rate variability.

Outcome measures

Outcome measures
Measure	Aerobic Exercise Group n=61 Participants This is the experimental group. Exercise is prescribed for 150 min/week. Due to COVID-19 restrictions the exercise supervision was allowed to be either remotely or in the context of a laboratory setting. Aerobic Exercise Group: Guidelines for exercise programming (ACSM, 2018) will be followed including a warm up and cool down, progressive and gradual increments in duration, and instruction regarding avoidance of physical activity related injury. The exercise group will receive moderate to vigorous intensity aerobic exercise targeting 150 minutes per week for 12 months. The group will target dividing these minutes into 3 exercise sessions a week. The prescribed intensity will be based on their maximal fitness testing heart rate and then calculated per a research grade method. They will maintain a minimum heart rate from their specific calculation that will be monitored by Polar Heart Rate straps.	Physical Activity & Health Information Group n=62 Participants This is the control group. Participants will engage in daily life monitoring every 6 weeks. Physical Activity \& Health Information Group: This group will not partake in the aerobic fitness sessions but will be asked to wear a daily monitoring device every 6 weeks. They will also complete all baseline, 6-month (optional), and 12-month visits.
Change in Heart Rate Variability (HRV)	0.0022 ln[ms²] Interval -0.257 to 0.261	-0.2035 ln[ms²] Interval -0.472 to 0.065

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline & 12 months

Changes in task invoked activity will be measured during an emotion regulation task.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 6-month (if applicable) & 12 months

Participants will complete the Emotion Regulation Questionnaire (ERQ). They rate how strongly they agree with 10 statements and emotion regulation abilities are calculated by their responses. A minimum score would be 10 and a maximum score would be 70, with 70 indicating superior emotion regulation abilities.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 6-month (if applicable) & 12 months

This will be calculated via the PSS 4-item scale. Scores are calculated by averaging responses from 10 questions with a minimum score of 0 and a maximum score of 40. 40 indicates more stress.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 6-month (if applicable) & 12 months

Participants will complete a questionnaire related to self-esteem via the Rosenberg Self Esteem Scale. All items are answered using a 4-point Likert scale format ranging from strongly agree to strongly disagree. Sum scores for all 10 items are calculated with items 2, 5, 6, 8, 9 being reverse scored. Higher scores indicate higher self-esteem.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 6-month (if applicable), & 12 months

An average systolic blood pressure (SBP) will be calculated for an average over all baseline, 6-month (if applicable) and 12-month visits.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 6-month (if applicable), & 12-month

Fitness is assessed by maximal graded exercise testing. Oxygen uptake (VO2) will be measured from expired air samples taken at 15s intervals until a peak VO2, the highest VO2, is attained at the point of test termination due to symptom limitation and/or volitional exhaustion.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 6-month (if applicable) & 12 month

Blood will be drawn at 3 time points throughout the intervention starting at baseline to measure changes in fasting glucose.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 6-month (if applicable) & 12 month

Blood will be drawn at 3 time points throughout the intervention starting at baseline to measure changes in insulin resistance.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 6 month (if applicable) and 12 month.

The outcome will be measured by whether the statistical mediation model that contains brain and peripheral physiological mediators is significant. By definition such a model must contain multiple outcome variables, but the outcome here isn't a measurable outcome but rather whether the statistical model with these variables reaches statistical significance.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 6-month (if applicable), & 12 months

An average heart rate will be calculated for an average over all baseline, 6-month (if applicable) and 12-month visits.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline & 12 months

Participants will complete several questions on a smart phone at various times throughout the day based on a prompt to learn more about positive and negative affect. An average positive and negative affect score will be computed.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline & 12 months

Participants will have their blood pressure taken while answering questions about daily stressors and an average SBP score will be computed over the course of the wear period.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline & 12 months

This will be calculated via scores from the Positive and Negative Affect Scale. Scores can range from 1 to 100, with 1 meaning less positive affect and 100 meaning more positive affect.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline & 12 months

Participants will have electrodes placed on their skin to record an EKG as well as a blood pressure cuff on their arm. BRS will be derived in part from the EKG signal.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline & 12 months

Participants will have electrodes placed on their skin to record an EKG as well as a blood pressure cuff on their arm. PWV will be derived in part from the EKG signal.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline & 12 months

Participants will have electrodes placed on their skin to record an EKG as well as a blood pressure cuff on their arm. Vasodilation (reactive hyperemia) will be derived in part from the EKG signal.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline & 12 months

MRI will be used to measure changes in brain activity including task invoked activation patterns.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline & 12 months

MRI will be used to measure changes in functional connectivity during rest.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline & 12 months

MRI will be used to measure cortical thickness. Measured in mm3.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline & 12 months

MRI will be used to measure cortical volume. Measured in mm3.

Outcome measures

Outcome data not reported

Adverse Events

Aerobic Exercise Group

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Physical Activity & Health Information Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Aerobic Exercise Group n=64 participants at risk This is the experimental group. Exercise is prescribed for 150 min/week. Due to COVID-19 restrictions the exercise supervision was allowed to be either remotely or in the context of a laboratory setting. Aerobic Exercise Group: Guidelines for exercise programming (ACSM, 2018) will be followed including a warm up and cool down, progressive and gradual increments in duration, and instruction regarding avoidance of physical activity related injury. The exercise group will receive moderate to vigorous intensity aerobic exercise targeting 150 minutes per week for 12 months. The group will target dividing these minutes into 3 exercise sessions a week. The prescribed intensity will be based on their maximal fitness testing heart rate and then calculated per a research grade method. They will maintain a minimum heart rate from their specific calculation that will be monitored by Polar Heart Rate straps.	Physical Activity & Health Information Group n=66 participants at risk This is the control group. Participants will engage in daily life monitoring every 6 weeks. Physical Activity \& Health Information Group: This group will not partake in the aerobic fitness sessions but will be asked to wear a daily monitoring device every 6 weeks. They will also complete all baseline, 6-month (optional), and 12-month visits.
Surgical and medical procedures Tumor	1.6% 1/64 • 1 year	0.00% 0/66 • 1 year

Other adverse events

Other adverse events
Measure	Aerobic Exercise Group n=64 participants at risk This is the experimental group. Exercise is prescribed for 150 min/week. Due to COVID-19 restrictions the exercise supervision was allowed to be either remotely or in the context of a laboratory setting. Aerobic Exercise Group: Guidelines for exercise programming (ACSM, 2018) will be followed including a warm up and cool down, progressive and gradual increments in duration, and instruction regarding avoidance of physical activity related injury. The exercise group will receive moderate to vigorous intensity aerobic exercise targeting 150 minutes per week for 12 months. The group will target dividing these minutes into 3 exercise sessions a week. The prescribed intensity will be based on their maximal fitness testing heart rate and then calculated per a research grade method. They will maintain a minimum heart rate from their specific calculation that will be monitored by Polar Heart Rate straps.	Physical Activity & Health Information Group n=66 participants at risk This is the control group. Participants will engage in daily life monitoring every 6 weeks. Physical Activity \& Health Information Group: This group will not partake in the aerobic fitness sessions but will be asked to wear a daily monitoring device every 6 weeks. They will also complete all baseline, 6-month (optional), and 12-month visits.
Vascular disorders Cardiovascular	1.6% 1/64 • 1 year	0.00% 0/66 • 1 year
Musculoskeletal and connective tissue disorders Musculoskeletal	7.8% 5/64 • 1 year	0.00% 0/66 • 1 year

Additional Information

Dr. Kirk I. Erickson

AdventHealth Research Institute

Phone: 4125763724

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place