ESRD
Conditions
Brief summary
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
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.
Interventions
OTHERCognitive training
The investigators will provide participants with tablets to play brain games.
OTHERExercise training
The investigators will provide participants with foot peddlers.
OTHERCombined 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.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Executive Function as Assessed by the Trail Making Test Assessment (TMT) | 3 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Completing Executive Function as Measured by the Stroop Test | 3 months | 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. |
| Change in Executive Function as Measured by the Digit Symbol Substitution Test | baseline and 3 months | 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. |
| Change in Physical Function as Measured by the Short Physical Performance Battery (SPPB) Test | Baseline and 3 months | 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. |
| Number of Participants With an Injurious Fall | 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 |
| Number of Participants With a Hospitalizations | 12 months | The number of participants with a hospitalizations during the 6 months of interventions and 6 months after the interventions |
| Change in Global Cognitive Function as Measured by the Montreal Cognitive Assessment (MoCA) | Baseline, 3 months | 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. |
| Change in Patient-centered Outcomes as Measured by the Kidney Disease Quality of Life (KDQOL) Survey | Baseline and 3 months | 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. |
| Change in Patient-centered Outcomes as Measured by the Patient-Reported Outcomes Measurement Information System (PROMIS)-29 | Baseline and 3 months | 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. |
| Number of Participants With an Amputation | 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 |
| Number of Participants Able to Return to Work | 12 months | The number of participants able to return to work during the 6 months of interventions and 6 months after interventions. |
| Mortality | 18 months | Mortality will be ascertained within the 6 months of the intervention and 1 year after the intervention (1.5 years total). |
Countries
United States
Participant flow
Recruitment details
The study was stopped after enrolling 130 participants by the Data Safety Monitoring Board (DSMB) due to COVID-19 shutdowns.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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 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. | 31 |
| Exercise Training 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. | 29 |
| 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. | 35 |
| Standard of Care Participants in this arm will receive standard of care | 26 |
| Total | 121 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 2 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 2 | 1 | 0 | 2 |
| Overall Study | Not specified or change in eligibility | 2 | 3 | 3 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 5 | 1 |
Baseline characteristics
| Characteristic | Exercise Training | Combined Cognitive and Exercise Training | Cognitive Training | Standard of Care | Total |
|---|---|---|---|---|---|
| Age, Continuous | 58.4 years | 60.4 years | 64.2 years | 60.4 years | 61.5 years |
| Race/Ethnicity, Customized Asian/Asian American | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized Black/African American | 22 Participants | 23 Participants | 25 Participants | 19 Participants | 89 Participants |
| Race/Ethnicity, Customized White/Caucasian | 7 Participants | 9 Participants | 5 Participants | 6 Participants | 27 Participants |
| Region of Enrollment United States | 29 Participants | 35 Participants | 31 Participants | 26 Participants | 121 Participants |
| Sex: Female, Male Female | 10 Participants | 14 Participants | 11 Participants | 10 Participants | 45 Participants |
| Sex: Female, Male Male | 19 Participants | 21 Participants | 20 Participants | 16 Participants | 76 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 6 / 31 | 4 / 29 | 3 / 35 | 4 / 26 |
| other Total, other adverse events | 24 / 31 | 21 / 29 | 28 / 35 | 12 / 26 |
| serious Total, serious adverse events | 6 / 31 | 1 / 29 | 4 / 35 | 0 / 26 |
Outcome results
Primary
Change in Executive Function as Assessed by the Trail Making Test Assessment (TMT)
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitive Training | Change in Executive Function as Assessed by the Trail Making Test Assessment (TMT) | 20.4 seconds | Standard Deviation 54.9 |
| Exercise Training | Change in Executive Function as Assessed by the Trail Making Test Assessment (TMT) | -0.8 seconds | Standard Deviation 82 |
| Combined Cognitive and Exercise Training | Change in Executive Function as Assessed by the Trail Making Test Assessment (TMT) | -5.6 seconds | Standard Deviation 101.7 |
| Standard of Care | Change in Executive Function as Assessed by the Trail Making Test Assessment (TMT) | 5.7 seconds | Standard Deviation 53.2 |
Secondary
Change in Executive Function as Measured by the Digit Symbol Substitution Test
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitive Training | Change in Executive Function as Measured by the Digit Symbol Substitution Test | 3.6 score on a scale | Standard Deviation 12.8 |
| Exercise Training | Change in Executive Function as Measured by the Digit Symbol Substitution Test | 6.4 score on a scale | Standard Deviation 15.6 |
| Combined Cognitive and Exercise Training | Change in Executive Function as Measured by the Digit Symbol Substitution Test | 2.0 score on a scale | Standard Deviation 18.9 |
| Standard of Care | Change in Executive Function as Measured by the Digit Symbol Substitution Test | .7 score on a scale | Standard Deviation 20 |
Secondary
Change in Global Cognitive Function as Measured by the Montreal Cognitive Assessment (MoCA)
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.
Time frame: Baseline, 3 months
Population: Participants with an available MoCA at baseline and 3-month follow-up were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitive Training | Change in Global Cognitive Function as Measured by the Montreal Cognitive Assessment (MoCA) | -0.1 score on a scale | Standard Deviation 2.9 |
| Exercise Training | Change in Global Cognitive Function as Measured by the Montreal Cognitive Assessment (MoCA) | 0.1 score on a scale | Standard Deviation 2.1 |
| Combined Cognitive and Exercise Training | Change in Global Cognitive Function as Measured by the Montreal Cognitive Assessment (MoCA) | 1.5 score on a scale | Standard Deviation 3.1 |
| Standard of Care | Change in Global Cognitive Function as Measured by the Montreal Cognitive Assessment (MoCA) | -0.6 score on a scale | Standard Deviation 3.3 |
Secondary
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. 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.
Time frame: Baseline and 3 months
Population: Participants with available KDQOL at baseline and 3-month follow-up were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitive Training | 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 |
| Exercise Training | Change in Patient-centered Outcomes as Measured by the Kidney Disease Quality of Life (KDQOL) Survey | 0.2 units on a scale | Standard Deviation 1.1 |
| Combined Cognitive and Exercise Training | Change in Patient-centered Outcomes as Measured by the Kidney Disease Quality of Life (KDQOL) Survey | 0.2 units on a scale | Standard Deviation 0.7 |
| Standard of Care | Change in Patient-centered Outcomes as Measured by the Kidney Disease Quality of Life (KDQOL) Survey | 0.3 units on a scale | Standard Deviation 1 |
Secondary
Change in Patient-centered Outcomes as Measured by the Patient-Reported Outcomes Measurement Information System (PROMIS)-29
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.
Time frame: Baseline and 3 months
Population: Only participants with available PROMIS-29 at baseline and 3 months were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitive Training | 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 |
| Exercise Training | Change in Patient-centered Outcomes as Measured by the Patient-Reported Outcomes Measurement Information System (PROMIS)-29 | -0.4 score on a scale | Standard Deviation 13.5 |
| Combined Cognitive and Exercise Training | Change in Patient-centered Outcomes as Measured by the Patient-Reported Outcomes Measurement Information System (PROMIS)-29 | -3.9 score on a scale | Standard Deviation 19.8 |
| Standard of Care | Change in Patient-centered Outcomes as Measured by the Patient-Reported Outcomes Measurement Information System (PROMIS)-29 | -5.6 score on a scale | Standard Deviation 17.2 |
Secondary
Change in Physical Function as Measured by the Short Physical Performance Battery (SPPB) Test
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.
Time frame: Baseline and 3 months
Population: Participants with an available SPPB at baseline and 3-month follow-up were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitive Training | Change in Physical Function as Measured by the Short Physical Performance Battery (SPPB) Test | -1.5 score on a scale | Standard Deviation 3.9 |
| Exercise Training | Change in Physical Function as Measured by the Short Physical Performance Battery (SPPB) Test | -1.7 score on a scale | Standard Deviation 3.8 |
| Combined Cognitive and Exercise Training | Change in Physical Function as Measured by the Short Physical Performance Battery (SPPB) Test | -0.1 score on a scale | Standard Deviation 2.8 |
| Standard of Care | Change in Physical Function as Measured by the Short Physical Performance Battery (SPPB) Test | 0.1 score on a scale | Standard Deviation 1.8 |
Secondary
Mortality
Mortality will be ascertained within the 6 months of the intervention and 1 year after the intervention (1.5 years total).
Time frame: 18 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cognitive Training | Mortality | 6 Participants |
| Exercise Training | Mortality | 4 Participants |
| Combined Cognitive and Exercise Training | Mortality | 3 Participants |
| Standard of Care | Mortality | 4 Participants |
Secondary
Number of Participants Able to Return to Work
The number of participants able to return to work during the 6 months of interventions and 6 months after interventions.
Time frame: 12 months
Population: Among those who were unemployed or on leave of absence at baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cognitive Training | Number of Participants Able to Return to Work | 1 Participants |
| Exercise Training | Number of Participants Able to Return to Work | 0 Participants |
| Combined Cognitive and Exercise Training | Number of Participants Able to Return to Work | 0 Participants |
| Standard of Care | Number of Participants Able to Return to Work | 0 Participants |
Secondary
Number of Participants Completing Executive Function as Measured by the Stroop Test
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.
Time frame: 3 months
Population: Participants with an available Stroop test at 3-month follow-up were included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cognitive Training | Number of Participants Completing Executive Function as Measured by the Stroop Test | 16 participants |
| Exercise Training | Number of Participants Completing Executive Function as Measured by the Stroop Test | 14 participants |
| Combined Cognitive and Exercise Training | Number of Participants Completing Executive Function as Measured by the Stroop Test | 19 participants |
| Standard of Care | Number of Participants Completing Executive Function as Measured by the Stroop Test | 13 participants |
Secondary
Number of Participants With a Hospitalizations
The number of participants with a hospitalizations during the 6 months of interventions and 6 months after the interventions
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cognitive Training | Number of Participants With a Hospitalizations | 12 Participants |
| Exercise Training | Number of Participants With a Hospitalizations | 7 Participants |
| Combined Cognitive and Exercise Training | Number of Participants With a Hospitalizations | 11 Participants |
| Standard of Care | Number of Participants With a Hospitalizations | 7 Participants |
Secondary
Number of Participants With an Amputation
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
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cognitive Training | Number of Participants With an Amputation | 0 Participants |
| Exercise Training | Number of Participants With an Amputation | 0 Participants |
| Combined Cognitive and Exercise Training | Number of Participants With an Amputation | 0 Participants |
| Standard of Care | Number of Participants With an Amputation | 0 Participants |
Secondary
Number of Participants With an Injurious Fall
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
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cognitive Training | Number of Participants With an Injurious Fall | 0 Participants |
| Exercise Training | Number of Participants With an Injurious Fall | 1 Participants |
| Combined Cognitive and Exercise Training | Number of Participants With an Injurious Fall | 0 Participants |
| Standard of Care | Number of Participants With an Injurious Fall | 0 Participants |