Trial Outcomes & Findings for Interventions Made to Preserve Cognitive Function (NCT NCT03616535)

NCT ID: NCT03616535

Last Updated: 2025-07-16

Results Overview

Change in executive function between baseline and 3 months as assessed by the Trail Making Test which is comprised of Part A and Part B. Executive function is assessed by the time (seconds) to complete Part B minus the time (seconds) to complete Part A. Needing more time to complete the test indicates worse executive function.

• Recruitment status: TERMINATED
• Study phase: NA
• Target enrollment: 130 participants
• Primary outcome timeframe: 3 months
• Results posted on: 2025-07-16

Participant Flow

The study was stopped after enrolling 130 participants by the Data Safety Monitoring Board (DSMB) due to COVID-19 shutdowns.

130 participants were consented. There were 9 participants who were consented but not randomized due to COVID-19 shutdowns. They are not included in the results.

Participant milestones

Measure	Cognitive Training Participants randomized to CT will play "brain games" on a tablet. They will be asked to engage in the activity for a minimum of 30 minutes during each hemodialysis (HD) session. At each HD session, participants will have 10 different brain games to play and the games will vary for each session. Cognitive training: The investigators will provide participants with tablets to play brain games.	Exercise Training Participants randomized to the Exercise Training (ET) arm will be given a stationary foot peddler and will be asked to engage in the activity for a minimum of 30 minutes at each hemodialysis session. ET will start with a 2 minute warm up, then the resistance will be adjusted so that participants are working at perceived exertion of "somewhat strong," using the Borg scale (87) (\~50 rpm). Resistance will be increased when the rating falls below "somewhat hard." Exercise training: The investigators will provide participants with foot peddlers.	Combined Cognitive and Exercise Training Participants in the CT+ET arm will start with 30 minutes of CT (playing "brain games" on tablet) with a 15-minute break, and then, 30 minutes of ET (stationary foot peddler). Combined cognitive and exercise training: The investigators will provide participants with tablets to play brain games for cognitive training and stationary foot peddlers for exercise training.	Standard of Care Participants in this arm will receive standard of care
Overall Study STARTED	31	29	35	26
Overall Study COMPLETED	24	23	27	21
Overall Study NOT COMPLETED	7	6	8	5

Reasons for withdrawal

Measure	Cognitive Training Participants randomized to CT will play "brain games" on a tablet. They will be asked to engage in the activity for a minimum of 30 minutes during each hemodialysis (HD) session. At each HD session, participants will have 10 different brain games to play and the games will vary for each session. Cognitive training: The investigators will provide participants with tablets to play brain games.	Exercise Training Participants randomized to the Exercise Training (ET) arm will be given a stationary foot peddler and will be asked to engage in the activity for a minimum of 30 minutes at each hemodialysis session. ET will start with a 2 minute warm up, then the resistance will be adjusted so that participants are working at perceived exertion of "somewhat strong," using the Borg scale (87) (\~50 rpm). Resistance will be increased when the rating falls below "somewhat hard." Exercise training: The investigators will provide participants with foot peddlers.	Combined Cognitive and Exercise Training Participants in the CT+ET arm will start with 30 minutes of CT (playing "brain games" on tablet) with a 15-minute break, and then, 30 minutes of ET (stationary foot peddler). Combined cognitive and exercise training: The investigators will provide participants with tablets to play brain games for cognitive training and stationary foot peddlers for exercise training.	Standard of Care Participants in this arm will receive standard of care
Overall Study Death	2	0	0	1
Overall Study Lost to Follow-up	2	1	0	2
Overall Study Withdrawal by Subject	1	2	5	1
Overall Study Not specified or change in eligibility	2	3	3	1

Baseline Characteristics

Interventions Made to Preserve Cognitive Function

Baseline characteristics by cohort

Measure	Cognitive Training n=31 Participants Participants randomized to CT will play "brain games" on a tablet. They will be asked to engage in the activity for a minimum of 30 minutes during each hemodialysis session. At each HD session, participants will have 10 different brain games to play and the games will vary for each session. Cognitive training: The investigators will provide participants with tablets to play brain games.	Exercise Training n=29 Participants Participants randomized to the ET arm will be given a stationary foot peddler and will be asked to engage in the activity for a minimum of 30 minutes at each hemodialysis session . ET will start with a 2 minute warm up, then the resistance will be adjusted so that participants are working at perceived exertion of "somewhat strong," using the Borg scale (87) (\~50 rpm). Resistance will be increased when the rating falls below "somewhat hard." Exercise training: The investigators will provide participants with foot peddlers.	Combined Cognitive and Exercise Training n=35 Participants Participants in the CT+ET arm will start with 30 minutes of CT (playing "brain games" on tablet) with a 15-minute break, and then, 30 minutes of ET (stationary foot peddler). Combined cognitive and exercise training: The investigators will provide participants with tablets to play brain games for cognitive training and stationary foot peddlers for exercise training.	Standard of Care n=26 Participants Participants in this arm will receive standard of care	Total n=121 Participants Total of all reporting groups
Age, Continuous	64.2 years n=5 Participants	58.4 years n=7 Participants	60.4 years n=5 Participants	60.4 years n=4 Participants	61.5 years n=21 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	10 Participants n=7 Participants	14 Participants n=5 Participants	10 Participants n=4 Participants	45 Participants n=21 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	19 Participants n=7 Participants	21 Participants n=5 Participants	16 Participants n=4 Participants	76 Participants n=21 Participants
Race/Ethnicity, Customized White/Caucasian	5 Participants n=5 Participants	7 Participants n=7 Participants	9 Participants n=5 Participants	6 Participants n=4 Participants	27 Participants n=21 Participants
Race/Ethnicity, Customized Black/African American	25 Participants n=5 Participants	22 Participants n=7 Participants	23 Participants n=5 Participants	19 Participants n=4 Participants	89 Participants n=21 Participants
Race/Ethnicity, Customized Asian/Asian American	1 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	1 Participants n=4 Participants	5 Participants n=21 Participants
Region of Enrollment United States	31 Participants n=5 Participants	29 Participants n=7 Participants	35 Participants n=5 Participants	26 Participants n=4 Participants	121 Participants n=21 Participants

PRIMARY outcome

Timeframe: 3 months

Population: Due to COVID-19 shutdowns, the trial was terminated early by the DSMB. All participants with available TMT A/B at baseline and 3 months of follow-up were analyzed.

Change in executive function between baseline and 3 months as assessed by the Trail Making Test which is comprised of Part A and Part B. Executive function is assessed by the time (seconds) to complete Part B minus the time (seconds) to complete Part A. Needing more time to complete the test indicates worse executive function.

Outcome measures

Measure	Cognitive Training n=24 Participants Participants randomized to CT will play "brain games" on a tablet. They will be asked to engage in the activity for a minimum of 30 minutes during each hemodialysis session. At each HD session, participants will have 10 different brain games to play and the games will vary for each session. Cognitive training: The investigators will provide participants with tablets to play brain games.	Exercise Training n=23 Participants Participants randomized to the ET arm will be given a stationary foot peddler and will be asked to engage in the activity for a minimum of 30 minutes at each hemodialysis session . ET will start with a 2 minute warm up, then the resistance will be adjusted so that participants are working at perceived exertion of "somewhat strong," using the Borg scale (87) (\~50 rpm). Resistance will be increased when the rating falls below "somewhat hard." Exercise training: The investigators will provide participants with foot peddlers.	Combined Cognitive and Exercise Training n=27 Participants Participants in the CT+ET arm will start with 30 minutes of CT (playing "brain games" on tablet) with a 15-minute break, and then, 30 minutes of ET (stationary foot peddler). Combined cognitive and exercise training: The investigators will provide participants with tablets to play brain games for cognitive training and stationary foot peddlers for exercise training.	Standard of Care n=21 Participants Participants in this arm will receive standard of care
Change in Executive Function as Assessed by the Trail Making Test Assessment (TMT)	20.4 seconds Standard Deviation 54.9	-0.8 seconds Standard Deviation 82	-5.6 seconds Standard Deviation 101.7	5.7 seconds Standard Deviation 53.2

SECONDARY outcome

Timeframe: Baseline, 3 months

Population: Participants with an available MoCA at baseline and 3-month follow-up were included in this analysis.

Change in global cognitive function at 3-months of interventions as measured by the Montreal Cognitive Assessment (MoCA). It is a brief 30 question test that assesses different cognitive domains: attention and concentration, executive functions, memory, language, visual construction skills, conceptual thinking, calculations, and orientation. Total possible score range is 0-30 points, and a score of 26 or above is considered normal.

Outcome measures

Measure	Cognitive Training n=20 Participants Participants randomized to CT will play "brain games" on a tablet. They will be asked to engage in the activity for a minimum of 30 minutes during each hemodialysis session. At each HD session, participants will have 10 different brain games to play and the games will vary for each session. Cognitive training: The investigators will provide participants with tablets to play brain games.	Exercise Training n=17 Participants Participants randomized to the ET arm will be given a stationary foot peddler and will be asked to engage in the activity for a minimum of 30 minutes at each hemodialysis session . ET will start with a 2 minute warm up, then the resistance will be adjusted so that participants are working at perceived exertion of "somewhat strong," using the Borg scale (87) (\~50 rpm). Resistance will be increased when the rating falls below "somewhat hard." Exercise training: The investigators will provide participants with foot peddlers.	Combined Cognitive and Exercise Training n=22 Participants Participants in the CT+ET arm will start with 30 minutes of CT (playing "brain games" on tablet) with a 15-minute break, and then, 30 minutes of ET (stationary foot peddler). Combined cognitive and exercise training: The investigators will provide participants with tablets to play brain games for cognitive training and stationary foot peddlers for exercise training.	Standard of Care n=18 Participants Participants in this arm will receive standard of care
Change in Global Cognitive Function as Measured by the Montreal Cognitive Assessment (MoCA)	-0.1 score on a scale Standard Deviation 2.9	0.1 score on a scale Standard Deviation 2.1	1.5 score on a scale Standard Deviation 3.1	-0.6 score on a scale Standard Deviation 3.3

SECONDARY outcome

Timeframe: 3 months

Population: Participants with an available Stroop test at 3-month follow-up were included in this analysis.

Number completing the Stroop test of executive function at 3 months of interventions. The Stroop test asks participants to view two conflicting pieces of information, specifically the word itself and the color of the ink it's printed in. Participants are asked to name the color of the ink used to print words, rather than reading the words themselves.

Outcome measures

Measure	Cognitive Training n=16 Participants Participants randomized to CT will play "brain games" on a tablet. They will be asked to engage in the activity for a minimum of 30 minutes during each hemodialysis session. At each HD session, participants will have 10 different brain games to play and the games will vary for each session. Cognitive training: The investigators will provide participants with tablets to play brain games.	Exercise Training n=16 Participants Participants randomized to the ET arm will be given a stationary foot peddler and will be asked to engage in the activity for a minimum of 30 minutes at each hemodialysis session . ET will start with a 2 minute warm up, then the resistance will be adjusted so that participants are working at perceived exertion of "somewhat strong," using the Borg scale (87) (\~50 rpm). Resistance will be increased when the rating falls below "somewhat hard." Exercise training: The investigators will provide participants with foot peddlers.	Combined Cognitive and Exercise Training n=22 Participants Participants in the CT+ET arm will start with 30 minutes of CT (playing "brain games" on tablet) with a 15-minute break, and then, 30 minutes of ET (stationary foot peddler). Combined cognitive and exercise training: The investigators will provide participants with tablets to play brain games for cognitive training and stationary foot peddlers for exercise training.	Standard of Care n=14 Participants Participants in this arm will receive standard of care
Number of Participants Completing Executive Function as Measured by the Stroop Test	16 participants	14 participants	19 participants	13 participants

SECONDARY outcome

Timeframe: baseline and 3 months

Population: Participants with an available Digit Symbol Substitution Test at baseline and 3-month follow-up were included in this analysis.

Change in executive function at 3 months of interventions as measure by the Digit Symbol Substitution Test. This test evaluates the speed and working memory components of executive function. It involves a key consisting of the numbers 1-9, each paired with a unique, easy-to--draw symbol such as a "V", "+" or ">". Below the key are a series of the numbers 1-9 in random order and repeated several times. The participant is allowed 90 seconds to fill in the corresponding symbol for each number. This task requires the individual to visually scan the answer key provided at the top of the test and then write the correct symbol by each number as quickly as possible. The correct number of symbols written within 90 seconds is measured. Total possible score ranges from a minimum of 0 to a maximum of 90 points. Higher scores represent better outcomes.

Outcome measures

Measure	Cognitive Training n=20 Participants Participants randomized to CT will play "brain games" on a tablet. They will be asked to engage in the activity for a minimum of 30 minutes during each hemodialysis session. At each HD session, participants will have 10 different brain games to play and the games will vary for each session. Cognitive training: The investigators will provide participants with tablets to play brain games.	Exercise Training n=19 Participants Participants randomized to the ET arm will be given a stationary foot peddler and will be asked to engage in the activity for a minimum of 30 minutes at each hemodialysis session . ET will start with a 2 minute warm up, then the resistance will be adjusted so that participants are working at perceived exertion of "somewhat strong," using the Borg scale (87) (\~50 rpm). Resistance will be increased when the rating falls below "somewhat hard." Exercise training: The investigators will provide participants with foot peddlers.	Combined Cognitive and Exercise Training n=23 Participants Participants in the CT+ET arm will start with 30 minutes of CT (playing "brain games" on tablet) with a 15-minute break, and then, 30 minutes of ET (stationary foot peddler). Combined cognitive and exercise training: The investigators will provide participants with tablets to play brain games for cognitive training and stationary foot peddlers for exercise training.	Standard of Care n=15 Participants Participants in this arm will receive standard of care
Change in Executive Function as Measured by the Digit Symbol Substitution Test	3.6 score on a scale Standard Deviation 12.8	6.4 score on a scale Standard Deviation 15.6	2.0 score on a scale Standard Deviation 18.9	.7 score on a scale Standard Deviation 20

SECONDARY outcome

Timeframe: Baseline and 3 months

Population: Participants with an available SPPB at baseline and 3-month follow-up were included in this analysis.

Change in lower extremity function at 3 months of interventions using the SPPB test. The SPPB is an objective assessment tool for evaluating lower extremity functioning This test is a performance-based assessment comprised of 3 tasks: 1) repeated chair stands, 2) standing balance, and 3) a 4-meter usual paced walk in those with and without a walking aid (meters/second). Participants receive a score of 0 for a task if they were unable to complete the task; otherwise, they receive scores of 1-4 based on population-based norms. The scores of the three tasks are summed to create the SPPB score. The SPPB score ranges from 0 to 12, with lower scores indicating poorer function.

Outcome measures

Measure	Cognitive Training n=22 Participants Participants randomized to CT will play "brain games" on a tablet. They will be asked to engage in the activity for a minimum of 30 minutes during each hemodialysis session. At each HD session, participants will have 10 different brain games to play and the games will vary for each session. Cognitive training: The investigators will provide participants with tablets to play brain games.	Exercise Training n=18 Participants Participants randomized to the ET arm will be given a stationary foot peddler and will be asked to engage in the activity for a minimum of 30 minutes at each hemodialysis session . ET will start with a 2 minute warm up, then the resistance will be adjusted so that participants are working at perceived exertion of "somewhat strong," using the Borg scale (87) (\~50 rpm). Resistance will be increased when the rating falls below "somewhat hard." Exercise training: The investigators will provide participants with foot peddlers.	Combined Cognitive and Exercise Training n=25 Participants Participants in the CT+ET arm will start with 30 minutes of CT (playing "brain games" on tablet) with a 15-minute break, and then, 30 minutes of ET (stationary foot peddler). Combined cognitive and exercise training: The investigators will provide participants with tablets to play brain games for cognitive training and stationary foot peddlers for exercise training.	Standard of Care n=16 Participants Participants in this arm will receive standard of care
Change in Physical Function as Measured by the Short Physical Performance Battery (SPPB) Test	-1.5 score on a scale Standard Deviation 3.9	-1.7 score on a scale Standard Deviation 3.8	-0.1 score on a scale Standard Deviation 2.8	0.1 score on a scale Standard Deviation 1.8

SECONDARY outcome

Timeframe: 12 months

Number of participants with an injurious falls resulting in a medical encounter during the 6 months of interventions and for 6 months after the interventions

Outcome measures

Measure	Cognitive Training n=31 Participants Participants randomized to CT will play "brain games" on a tablet. They will be asked to engage in the activity for a minimum of 30 minutes during each hemodialysis session. At each HD session, participants will have 10 different brain games to play and the games will vary for each session. Cognitive training: The investigators will provide participants with tablets to play brain games.	Exercise Training n=29 Participants Participants randomized to the ET arm will be given a stationary foot peddler and will be asked to engage in the activity for a minimum of 30 minutes at each hemodialysis session . ET will start with a 2 minute warm up, then the resistance will be adjusted so that participants are working at perceived exertion of "somewhat strong," using the Borg scale (87) (\~50 rpm). Resistance will be increased when the rating falls below "somewhat hard." Exercise training: The investigators will provide participants with foot peddlers.	Combined Cognitive and Exercise Training n=35 Participants Participants in the CT+ET arm will start with 30 minutes of CT (playing "brain games" on tablet) with a 15-minute break, and then, 30 minutes of ET (stationary foot peddler). Combined cognitive and exercise training: The investigators will provide participants with tablets to play brain games for cognitive training and stationary foot peddlers for exercise training.	Standard of Care n=26 Participants Participants in this arm will receive standard of care
Number of Participants With an Injurious Fall	0 Participants	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 12 months

The number of participants with a hospitalizations during the 6 months of interventions and 6 months after the interventions

Outcome measures

Measure	Cognitive Training n=31 Participants Participants randomized to CT will play "brain games" on a tablet. They will be asked to engage in the activity for a minimum of 30 minutes during each hemodialysis session. At each HD session, participants will have 10 different brain games to play and the games will vary for each session. Cognitive training: The investigators will provide participants with tablets to play brain games.	Exercise Training n=29 Participants Participants randomized to the ET arm will be given a stationary foot peddler and will be asked to engage in the activity for a minimum of 30 minutes at each hemodialysis session . ET will start with a 2 minute warm up, then the resistance will be adjusted so that participants are working at perceived exertion of "somewhat strong," using the Borg scale (87) (\~50 rpm). Resistance will be increased when the rating falls below "somewhat hard." Exercise training: The investigators will provide participants with foot peddlers.	Combined Cognitive and Exercise Training n=35 Participants Participants in the CT+ET arm will start with 30 minutes of CT (playing "brain games" on tablet) with a 15-minute break, and then, 30 minutes of ET (stationary foot peddler). Combined cognitive and exercise training: The investigators will provide participants with tablets to play brain games for cognitive training and stationary foot peddlers for exercise training.	Standard of Care n=26 Participants Participants in this arm will receive standard of care
Number of Participants With a Hospitalizations	12 Participants	7 Participants	11 Participants	7 Participants

SECONDARY outcome

Timeframe: 18 months

Mortality will be ascertained within the 6 months of the intervention and 1 year after the intervention (1.5 years total).

Outcome measures

Measure	Cognitive Training n=31 Participants Participants randomized to CT will play "brain games" on a tablet. They will be asked to engage in the activity for a minimum of 30 minutes during each hemodialysis session. At each HD session, participants will have 10 different brain games to play and the games will vary for each session. Cognitive training: The investigators will provide participants with tablets to play brain games.	Exercise Training n=29 Participants Participants randomized to the ET arm will be given a stationary foot peddler and will be asked to engage in the activity for a minimum of 30 minutes at each hemodialysis session . ET will start with a 2 minute warm up, then the resistance will be adjusted so that participants are working at perceived exertion of "somewhat strong," using the Borg scale (87) (\~50 rpm). Resistance will be increased when the rating falls below "somewhat hard." Exercise training: The investigators will provide participants with foot peddlers.	Combined Cognitive and Exercise Training n=35 Participants Participants in the CT+ET arm will start with 30 minutes of CT (playing "brain games" on tablet) with a 15-minute break, and then, 30 minutes of ET (stationary foot peddler). Combined cognitive and exercise training: The investigators will provide participants with tablets to play brain games for cognitive training and stationary foot peddlers for exercise training.	Standard of Care n=26 Participants Participants in this arm will receive standard of care
Mortality	6 Participants	4 Participants	3 Participants	4 Participants

SECONDARY outcome

Timeframe: Baseline and 3 months

Population: Participants with available KDQOL at baseline and 3-month follow-up were included in this analysis.

Change in kidney disease-specific physical and mental quality of life at 3 months. Using a single the question from the KDQOL: In general, would you say your health is ___ ? It is reported on a 5-point score: 1, poor; 2, fair; 3, good; 4, very good; 5, excellent. Higher is better. While the score of KDQOL ranges from 1 to 5 points, we are measuring the 3-month change in this score. Therefore, the change could range from -4 to 4 points.

Outcome measures

Measure	Cognitive Training n=23 Participants Participants randomized to CT will play "brain games" on a tablet. They will be asked to engage in the activity for a minimum of 30 minutes during each hemodialysis session. At each HD session, participants will have 10 different brain games to play and the games will vary for each session. Cognitive training: The investigators will provide participants with tablets to play brain games.	Exercise Training n=21 Participants Participants randomized to the ET arm will be given a stationary foot peddler and will be asked to engage in the activity for a minimum of 30 minutes at each hemodialysis session . ET will start with a 2 minute warm up, then the resistance will be adjusted so that participants are working at perceived exertion of "somewhat strong," using the Borg scale (87) (\~50 rpm). Resistance will be increased when the rating falls below "somewhat hard." Exercise training: The investigators will provide participants with foot peddlers.	Combined Cognitive and Exercise Training n=28 Participants Participants in the CT+ET arm will start with 30 minutes of CT (playing "brain games" on tablet) with a 15-minute break, and then, 30 minutes of ET (stationary foot peddler). Combined cognitive and exercise training: The investigators will provide participants with tablets to play brain games for cognitive training and stationary foot peddlers for exercise training.	Standard of Care n=18 Participants Participants in this arm will receive standard of care
Change in Patient-centered Outcomes as Measured by the Kidney Disease Quality of Life (KDQOL) Survey	-0.1 units on a scale Standard Deviation 1.1	0.2 units on a scale Standard Deviation 1.1	0.2 units on a scale Standard Deviation 0.7	0.3 units on a scale Standard Deviation 1.0

SECONDARY outcome

Timeframe: Baseline and 3 months

Population: Only participants with available PROMIS-29 at baseline and 3 months were included.

Change in Patient-centered Outcomes as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS)-29 The change in PROMIS-29 score at 3 months is reported. Scores range from 0-140; higher scores are better.

Outcome measures

Measure	Cognitive Training n=23 Participants Participants randomized to CT will play "brain games" on a tablet. They will be asked to engage in the activity for a minimum of 30 minutes during each hemodialysis session. At each HD session, participants will have 10 different brain games to play and the games will vary for each session. Cognitive training: The investigators will provide participants with tablets to play brain games.	Exercise Training n=21 Participants Participants randomized to the ET arm will be given a stationary foot peddler and will be asked to engage in the activity for a minimum of 30 minutes at each hemodialysis session . ET will start with a 2 minute warm up, then the resistance will be adjusted so that participants are working at perceived exertion of "somewhat strong," using the Borg scale (87) (\~50 rpm). Resistance will be increased when the rating falls below "somewhat hard." Exercise training: The investigators will provide participants with foot peddlers.	Combined Cognitive and Exercise Training n=27 Participants Participants in the CT+ET arm will start with 30 minutes of CT (playing "brain games" on tablet) with a 15-minute break, and then, 30 minutes of ET (stationary foot peddler). Combined cognitive and exercise training: The investigators will provide participants with tablets to play brain games for cognitive training and stationary foot peddlers for exercise training.	Standard of Care n=18 Participants Participants in this arm will receive standard of care
Change in Patient-centered Outcomes as Measured by the Patient-Reported Outcomes Measurement Information System (PROMIS)-29	7.3 score on a scale Standard Deviation 22.2	-0.4 score on a scale Standard Deviation 13.5	-3.9 score on a scale Standard Deviation 19.8	-5.6 score on a scale Standard Deviation 17.2

SECONDARY outcome

Timeframe: 12 months

The number of participants with an amputation during the 6 months of interventions and 6 months after interventions. This information will be either self-reported by the participant or abstracted from the medical records to see if the interventions are associated with amputations

Outcome measures

Measure	Cognitive Training n=31 Participants Participants randomized to CT will play "brain games" on a tablet. They will be asked to engage in the activity for a minimum of 30 minutes during each hemodialysis session. At each HD session, participants will have 10 different brain games to play and the games will vary for each session. Cognitive training: The investigators will provide participants with tablets to play brain games.	Exercise Training n=29 Participants Participants randomized to the ET arm will be given a stationary foot peddler and will be asked to engage in the activity for a minimum of 30 minutes at each hemodialysis session . ET will start with a 2 minute warm up, then the resistance will be adjusted so that participants are working at perceived exertion of "somewhat strong," using the Borg scale (87) (\~50 rpm). Resistance will be increased when the rating falls below "somewhat hard." Exercise training: The investigators will provide participants with foot peddlers.	Combined Cognitive and Exercise Training n=35 Participants Participants in the CT+ET arm will start with 30 minutes of CT (playing "brain games" on tablet) with a 15-minute break, and then, 30 minutes of ET (stationary foot peddler). Combined cognitive and exercise training: The investigators will provide participants with tablets to play brain games for cognitive training and stationary foot peddlers for exercise training.	Standard of Care n=26 Participants Participants in this arm will receive standard of care
Number of Participants With an Amputation	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 12 months

Population: Among those who were unemployed or on leave of absence at baseline

The number of participants able to return to work during the 6 months of interventions and 6 months after interventions.

Outcome measures

Measure	Cognitive Training n=3 Participants Participants randomized to CT will play "brain games" on a tablet. They will be asked to engage in the activity for a minimum of 30 minutes during each hemodialysis session. At each HD session, participants will have 10 different brain games to play and the games will vary for each session. Cognitive training: The investigators will provide participants with tablets to play brain games.	Exercise Training n=4 Participants Participants randomized to the ET arm will be given a stationary foot peddler and will be asked to engage in the activity for a minimum of 30 minutes at each hemodialysis session . ET will start with a 2 minute warm up, then the resistance will be adjusted so that participants are working at perceived exertion of "somewhat strong," using the Borg scale (87) (\~50 rpm). Resistance will be increased when the rating falls below "somewhat hard." Exercise training: The investigators will provide participants with foot peddlers.	Combined Cognitive and Exercise Training n=8 Participants Participants in the CT+ET arm will start with 30 minutes of CT (playing "brain games" on tablet) with a 15-minute break, and then, 30 minutes of ET (stationary foot peddler). Combined cognitive and exercise training: The investigators will provide participants with tablets to play brain games for cognitive training and stationary foot peddlers for exercise training.	Standard of Care n=3 Participants Participants in this arm will receive standard of care
Number of Participants Able to Return to Work	1 Participants	0 Participants	0 Participants	0 Participants

Adverse Events

Cognitive Training

Serious events: 6 serious events

Other events: 24 other events

Deaths: 6 deaths

Exercise Training

Serious events: 1 serious events

Other events: 21 other events

Deaths: 4 deaths

Combined Cognitive and Exercise Training

Serious events: 4 serious events

Other events: 28 other events

Deaths: 3 deaths

Standard of Care

Serious events: 0 serious events

Other events: 12 other events

Deaths: 4 deaths

Serious adverse events

Measure	Cognitive Training n=31 participants at risk Participants randomized to CT will play "brain games" on a tablet. They will be asked to engage in the activity for a minimum of 30 minutes during each hemodialysis session. At each HD session, participants will have 10 different brain games to play and the games will vary for each session. Cognitive training: The investigators will provide participants with tablets to play brain games.	Exercise Training n=29 participants at risk Participants randomized to the ET arm will be given a stationary foot peddler and will be asked to engage in the activity for a minimum of 30 minutes at each hemodialysis session. ET will start with a 2 minute warm up, then the resistance will be adjusted so that participants are working at perceived exertion of "somewhat strong," using the Borg scale (87) (\~50 rpm). Resistance will be increased when the rating falls below "somewhat hard." Exercise training: The investigators will provide participants with foot peddlers.	Combined Cognitive and Exercise Training n=35 participants at risk Participants in the CT+ET arm will start with 30 minutes of CT (playing "brain games" on tablet) with a 15-minute break, and then, 30 minutes of ET (stationary foot peddler). Combined cognitive and exercise training: The investigators will provide participants with tablets to play brain games for cognitive training and stationary foot peddlers for exercise training.	Standard of Care n=26 participants at risk Participants in this arm will receive standard of care
General disorders Hospitalization/Prolonged Hospitalization	19.4% 6/31 • Up to 18 months after enrollment for mortality; up to 12 months after enrollment for hospitalizations; all else up to 6 months.	3.4% 1/29 • Up to 18 months after enrollment for mortality; up to 12 months after enrollment for hospitalizations; all else up to 6 months.	11.4% 4/35 • Up to 18 months after enrollment for mortality; up to 12 months after enrollment for hospitalizations; all else up to 6 months.	0.00% 0/26 • Up to 18 months after enrollment for mortality; up to 12 months after enrollment for hospitalizations; all else up to 6 months.

Other adverse events

Measure	Cognitive Training n=31 participants at risk Participants randomized to CT will play "brain games" on a tablet. They will be asked to engage in the activity for a minimum of 30 minutes during each hemodialysis session. At each HD session, participants will have 10 different brain games to play and the games will vary for each session. Cognitive training: The investigators will provide participants with tablets to play brain games.	Exercise Training n=29 participants at risk Participants randomized to the ET arm will be given a stationary foot peddler and will be asked to engage in the activity for a minimum of 30 minutes at each hemodialysis session. ET will start with a 2 minute warm up, then the resistance will be adjusted so that participants are working at perceived exertion of "somewhat strong," using the Borg scale (87) (\~50 rpm). Resistance will be increased when the rating falls below "somewhat hard." Exercise training: The investigators will provide participants with foot peddlers.	Combined Cognitive and Exercise Training n=35 participants at risk Participants in the CT+ET arm will start with 30 minutes of CT (playing "brain games" on tablet) with a 15-minute break, and then, 30 minutes of ET (stationary foot peddler). Combined cognitive and exercise training: The investigators will provide participants with tablets to play brain games for cognitive training and stationary foot peddlers for exercise training.	Standard of Care n=26 participants at risk Participants in this arm will receive standard of care
Musculoskeletal and connective tissue disorders Cramp	45.2% 14/31 • Up to 18 months after enrollment for mortality; up to 12 months after enrollment for hospitalizations; all else up to 6 months.	44.8% 13/29 • Up to 18 months after enrollment for mortality; up to 12 months after enrollment for hospitalizations; all else up to 6 months.	42.9% 15/35 • Up to 18 months after enrollment for mortality; up to 12 months after enrollment for hospitalizations; all else up to 6 months.	26.9% 7/26 • Up to 18 months after enrollment for mortality; up to 12 months after enrollment for hospitalizations; all else up to 6 months.
General disorders Hypotension	22.6% 7/31 • Up to 18 months after enrollment for mortality; up to 12 months after enrollment for hospitalizations; all else up to 6 months.	37.9% 11/29 • Up to 18 months after enrollment for mortality; up to 12 months after enrollment for hospitalizations; all else up to 6 months.	48.6% 17/35 • Up to 18 months after enrollment for mortality; up to 12 months after enrollment for hospitalizations; all else up to 6 months.	0.00% 0/26 • Up to 18 months after enrollment for mortality; up to 12 months after enrollment for hospitalizations; all else up to 6 months.
General disorders Hypertension	38.7% 12/31 • Up to 18 months after enrollment for mortality; up to 12 months after enrollment for hospitalizations; all else up to 6 months.	34.5% 10/29 • Up to 18 months after enrollment for mortality; up to 12 months after enrollment for hospitalizations; all else up to 6 months.	28.6% 10/35 • Up to 18 months after enrollment for mortality; up to 12 months after enrollment for hospitalizations; all else up to 6 months.	15.4% 4/26 • Up to 18 months after enrollment for mortality; up to 12 months after enrollment for hospitalizations; all else up to 6 months.
Cardiac disorders Elevated heart rate	0.00% 0/31 • Up to 18 months after enrollment for mortality; up to 12 months after enrollment for hospitalizations; all else up to 6 months.	10.3% 3/29 • Up to 18 months after enrollment for mortality; up to 12 months after enrollment for hospitalizations; all else up to 6 months.	8.6% 3/35 • Up to 18 months after enrollment for mortality; up to 12 months after enrollment for hospitalizations; all else up to 6 months.	0.00% 0/26 • Up to 18 months after enrollment for mortality; up to 12 months after enrollment for hospitalizations; all else up to 6 months.
General disorders headache	19.4% 6/31 • Up to 18 months after enrollment for mortality; up to 12 months after enrollment for hospitalizations; all else up to 6 months.	24.1% 7/29 • Up to 18 months after enrollment for mortality; up to 12 months after enrollment for hospitalizations; all else up to 6 months.	37.1% 13/35 • Up to 18 months after enrollment for mortality; up to 12 months after enrollment for hospitalizations; all else up to 6 months.	15.4% 4/26 • Up to 18 months after enrollment for mortality; up to 12 months after enrollment for hospitalizations; all else up to 6 months.
General disorders other unexpected event	45.2% 14/31 • Up to 18 months after enrollment for mortality; up to 12 months after enrollment for hospitalizations; all else up to 6 months.	24.1% 7/29 • Up to 18 months after enrollment for mortality; up to 12 months after enrollment for hospitalizations; all else up to 6 months.	37.1% 13/35 • Up to 18 months after enrollment for mortality; up to 12 months after enrollment for hospitalizations; all else up to 6 months.	23.1% 6/26 • Up to 18 months after enrollment for mortality; up to 12 months after enrollment for hospitalizations; all else up to 6 months.

Additional Information

Dr. Mara McAdams DeMarco

NYU Grossman School of Medicine and Langone Health

Phone: 1-646-987-1358

Email: mara.mcadamsdemarco@nyulangone.org

Results disclosure agreements

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