Interventions Made to Preserve Cognitive Function

Study Overview
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Brief Summary
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This is a randomized, controlled trial to slow cognitive decline in adults undergoing hemodialysis (HD). The investigators will test three interventions cognitive training (CT), exercise training (ET), and combined cognitive and exercise training (CT+ET) relative to standard of care (SC).

Detailed Description
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This will be a two by two factorial, randomized, controlled trial to slow cognitive decline in adults undergoing hemodialysis (HD). The investigators primary objective is to determine if receiving cognitive training (tablet-based brain games), exercise training (stationary foot pedal), or combined cognitive and exercise training preserves executive function relative to those with standard of care . The secondary objectives are to compare the rates of end stage renal disease (ESRD)-specific clinical outcomes and patient centered outcomes among those receiving CT, or ET, or CT+ET relative to those in SC. The investigators will formally test whether receiving CT or ET will preserve executive function and receiving combined CT+ET will preserve executive function better than CT or ET alone.

Official Title
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Hemodialysis-based Interventions to Preserve Cognitive Function

Conditions
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ESRD

Intervention / Treatment
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* Other: Cognitive training
* Other: Exercise training
* Other: Combined cognitive and exercise training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years or older at enrollment English speaking within 3 months to 3 years of initiating hemodialysis receiving hemodialysis at participating dialysis centers Exclusion Criteria: Patients with the following conditions will be excluded: Pregnancy Angina Pectoris Chronic lung disease requiring oxygen Musculoskeletal conditions that limit mobility Upper or lower extremity amputation Orthopedic disorders exacerbated by physical activity Femoral arteriovenous (AV) access Hepatitis B infection Blindness/Legal blindness In addition to conditions outlined above, patients who are currently incarcerated will be excluded from the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cognitive training<br>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 for 6 months. At each HD session, participants will have 10 different brain games to play and the games will vary for each session. | Other: Cognitive training<br>* The investigators will provide participants with tablets to play brain games.<br>* Other names: CT;|
| Active Comparator: Exercise training<br>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 for 6 months. 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. | Other: Exercise training<br>* The investigators will provide participants with foot peddlers.<br>* Other names: ET;|
| Active Comparator: Combined cognitive and exercise training<br>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). | Other: Combined cognitive and exercise training<br>* The investigators will provide participants with tablets to play brain games for cognitive training and stationary foot peddlers for exercise training.<br>* Other names: CT+ET;|
| No Intervention: Standard of Care<br>Participants in this arm will receive standard of care | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3 month change in executive function | Change in executive function between baseline and 3 months of interventions as measured by the Trail Making Test which is comprised of Part A and Part B. Executive function is assessed by the time (minutes) to complete Part B minus the time (minutes) to complete Part A. Needing more time to complete the test indicates worse executive function. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Global Cognitive Function as measured by the Montreal Cognitive Assessment (MoCA) | Change in global cognitive function at 3-months and 6 months of interventions as measured by the Montreal Cognitive Assessment (MoCA). This test was designed as a rapid screening instrument for mild cognitive dysfunction. It is a brief 30 question test that assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation.Total possible score is 30 points and a score of 26 or above is considered normal. | 3 months and 6 months | 
| Change in Executive function as measured by the Stroop test | Change in executive function at 3 months and 6 months of interventions as measured by the Stroop Test. The Stroop test is a screening test for cognitive function test and evaluates the inhibitory control of executive function. It is a measure of the ability of the brain to sort out distracting or unnecessary information from the meaningful tasks. It involves reading the name of a color printed in a different color ink. The time ratio of color-word interference and color only tasks will be calculated. | 3 months and 6 months | 
| Change in Executive function as measured by the Digit Symbol Substitution Test | Change in executive function at 3 months and 6 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. | 3 months and 6 months | 
| Change in Physical function as measured by the Short Physical Performance Battery (SPPB) test | Change in lower extremity function at 3 months and 6 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. | 3 months and 6 months | 
| Number of Falls | Number of injurious falls resulting in a medical encounter during the 6 months of interventions and for 6 months after the interventions | 12 months | 
| Number of Hospitalizations | The number of hospitalizations parameterized as both the number of hospital admissions and number of days hospitalized during the 6 months of interventions and 6 months after the interventions | 12 months | 
| Mortality | Mortality will be captured through Center for Medicare and Medicaid Services (CMS) death notification or the National Death Index. Mortality will be ascertained within the 6 months of the intervention and 1 year after the intervention (1.5 years total). | 18 months | 
| Change in Patient-centered Outcomes as measured by the Kidney Disease Quality of Life (KDQOL) Survey | Change in kidney disease-specific physical and mental quality of life at 3 months and 6 months of interventions. The KDQOL s a kidney disease-specific measure of how kidney disease is impacting a participant's quality of life. It is a 36-item survey with 3 subscales including physical and mental health-related quality of life, and kidney disease-specific HRQOL. Each subscale is scored 0 to 100 with higher scores indicating better HRQOL. | 3 months and 6 months | 
| Change in Patient-centered Outcomes as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS)-29 | Change in the participants' physical, mental, and social health status at 3 months and 6 months of interventions. PROMIS-29 is a health-related quality of life survey which assesses each of the 7 PROMIS domains with 4 questions. Norm-based scores have been calculated for each domain on the PROMIS measures. High scores represent more of the domain being measured. Thus, on symptom-oriented domains of PROMIS-29 (anxiety, depression, fatigue, pain interference, and sleep disturbance), higher scores represent worse symptomatology. On the function-oriented domains (physical functioning and social role) higher scores represent better functioning. | 3 months and 6 months | 
| Amputations | the incidence (number) of amputations during the 6 months of interventions and 6 months after interventions. This information will be either self-reported by the participant or abstracted from their medical records to see if the interventions are associated with amputations | 12 months | 
| Return to work status | the number of participants able to return to work during the 6 months of interventions and 6 months after interventions. | 12 months |