Healing Hearts and Mending Minds in Older Adults Living With HIV

Study Overview
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Brief Summary
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The purpose of this study is to see if exercise is helpful for improving memory, concentration thinking abilities, physical function, and quality of life for adults aged 50 to 89 years living with HIV and who have two or more cardiovascular disease risk factors. The study will test two kinds of intervention exercises: one group will walk for exercise and the second group will stretch for exercise. Members of both interventions will be asked to participate in one-on-one interviews/assessments, measures of physical functioning, and some sessions with others who are also enrolled in the study.

Detailed Description
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This is a two arm, randomized controlled trial to test the longitudinal effects of the Let's Move Program (walking for exercise) compared to effects of the attention control Let's Flex Program (stretching for exercise) in participants aged 50 to 89 years living with HIV and who have two or more cardiovascular disease risk factors. Participants in both interventions will be asked to participate in one-on-one interviews/assessments, measures of physical functioning, and some sessions with others who are also enrolled in the study. Participants will participate in an in home exercise program for twelve weeks in which the study team will help identify maximum duration and intensity followed by a maintenance period for weeks 13-58.

Official Title
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Healing Hearts and Mending Minds in Older Adults Living With HIV

Conditions
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HIV, Cardiovascular Disease, AIDS

Intervention / Treatment
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* Behavioral: Let's Move Program
* Behavioral: Let's Flex Program
* Behavioral: Group Motivational Interviewing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV diagnosis English speaking Live independently within a 30-45 mile radius of Atlanta, Georgia Not involved in any structured exercise program or exercising 3 or more times per week for a minimum of 30 minutes Not involved in any weight loss program Not hospitalized within the last 60-days Clinically stable and on antiretroviral therapy (ART) 6 months before enrollment If taking statins, stable on medication for 3 months Score 3 or less on the verbal memory subtest of the Montreal Cognitive Assessment (MoCA) Less than 0.5 standard deviations (SD) below mean on the Oral Trail Making Test B Able to provide informed consent and pass a consent post-test Exclusion Criteria: Non sedentary (defined as engaging in > 30 minutes of moderately strenuous exercise 3 times or more a week) Medical or physical condition that would preclude participation in the exercise component of the study (e.g., severe arthritis or mobility problems, lower extremity amputations, joint replacement(s), balance disorders, dizziness, dyspnea on exertion (DOE) with moderate exertion, difficulty walking one block, recent falls, obvious injury to lower extremity, uncontrolled hypertension or diabetes, renal failure, blindness, or a history of angina with activity) Ischemic changes or inappropriate BP changes on baseline exercise (modified Balke or Bruce) treadmill test On oral corticosteroids (nasal, optical and inhaler corticosteroids allowed without restriction) , experiencing acute inflammation at time of baseline or follow-up testing (this will result in rescheduling of testing if no other exclusion criteria apply after 2 weeks) Presence of current opportunistic infection Any terminal illness Regular use of anti-inflammatory medications such as non-steroidal anti-inflammatory agents excluding low dose aspirin On anti-psychotics On tricyclic antidepressants On anti-depressants equal to the equivalent of more than 1 mg of Clonazepam On Lithium Women who are pregnant Severe learning disabilities, intellectual disabilities, schizophrenia, bipolar, psychotic disorders to minimize confounding effects on neurocognitive data Confounding neuro-medical conditions (e.g., active central nervous system (CNS) opportunistic infections, seizure disorders, head injury with loss of consciousness greater than 30 minutes, intracranial neoplasms, stroke with neurological or neuropsychiatric sequelae, and non-HIV-associated dementias) Meet criteria for any Substance Use Disorder or Major Depression within 6 months of evaluation Creatinine > 2.5 within the past 6 months Patient Health Questionnaire-2 (PHQ-2) score > 4 Completed 8 years or less of school Failed to pass post-consent test after three attempts Two or more positive drug screen tests Alcohol breathalyzer test result > 0.03

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 89 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Let's Move Program<br>Participants in this group will be asked to walk five times per week for twelve weeks for a minimum of 30 minutes in their home while wearing a heart rate monitor and a pedometer. Participants will then enter a maintenance exercise period for 65 weeks. | Behavioral: Let's Move Program<br>* Participants will be asked to walk five times per week for twelve weeks for a minimum of 30 minutes while wearing a heart rate monitor and a pedometer. Participants will also receive weekly telephone calls from a member of the research team to monitor walking progress and to change walking duration or intensity level based on their progress.After the twelve week period, participants will enter a maintenance exercise phase for weeks 13-17 in which they will be asked to maintain their exercise regimen.<br>Behavioral: Group Motivational Interviewing<br>* Participants will attend four separate group intervention sessions for 2.5 hours for four consecutive weeks at the beginning of the program. Groups will consist of 6-8 members and will focus on the rationale for aerobic exercise, barriers to exercise, finding time for exercise, how to set short and long term exercise goals, and use of self-monitoring to improve exercise engagement.<br>|
| Active Comparator: Let's Flex Program<br>Participants in this group will be asked to stretch five times per week for twelve weeks for a minimum of thirty minutes in their home. Participants will then enter a maintenance exercise period for 65 weeks. | Behavioral: Let's Flex Program<br>* Participants will be asked to stretch five times per week for twelve weeks for a minimum of 30 minutes. Participants will also receive weekly telephone calls from a member of the research team to monitor progress and to change duration or intensity level based on their progress.After the twelve week period, participants will enter a maintenance exercise phase for weeks 13-17 in which they will be asked to maintain their exercise regimen.<br>Behavioral: Group Motivational Interviewing<br>* Participants will attend four separate group intervention sessions for 2.5 hours for four consecutive weeks at the beginning of the program. Groups will consist of 6-8 members and will focus on the rationale for aerobic exercise, barriers to exercise, finding time for exercise, how to set short and long term exercise goals, and use of self-monitoring to improve exercise engagement.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stroop Color and Word Test Score | The Stroop Color and Word Test is a performance-based test of executive function and inhibitory responding. The participant is presented with a page with the words red, blue, and green printed 100 times in (20 words in 5 columns). Each word is printed in a different color of ink than the target word (e.g, the word red is printed in blue ink). Participants read the color of ink in which the word is printed as quickly are possible within a time limit. The correct number within the time limit is the score. Raw scores (unadjusted for age and education) range from 0-100. | Baseline, T1 (13-15 weeks post baseline), T2 (28-30 weeks post baseline), T3 ( 56-58 weeks post baseline) | 
| Trail Making Test Score | The Trail Making Test is a performance based test of visual attention and task switching. It consists of two parts in which the subject is instructed to connect circles as possible while still maintaining accuracy. Trails A subtest requires the connection in sequence of 25 circles labeled by numbers. Trails B requires the connection in sequence of 25 circles labeled by alternating numbers and letters (1-A-2-B-3-C). The score on the test is the time in seconds that it takes to complete. Higher scores (i.e., time) indicate poorer performance. | Baseline, T1 (13-15 weeks post baseline), T2 (28-30 weeks post baseline), T3 ( 56-58 weeks post baseline) | 
| Letter Fluency Assessed by Change in FAS Test Score | The FAS test requires stating out loud as many words that begin with the assigned letter (F, A, and S) as possible within 60-seconds. Results represent total number of words stated for F,A & S combined. | Baseline, T1 (13-15 weeks post baseline), T2 (28-30 weeks post baseline), T3 ( 56-58 weeks post baseline) | 
| Category Fluency Test Score | The category fluency test requires participants to state out load the names of as many animals as possible within 60-seconds. Results are total number of animals named. | Baseline, T1 (13-15 weeks post baseline), T2 (28-30 weeks post baseline), T3 ( 56-58 weeks post baseline) | 
| Hopkins Verbal Learning Test (HVLT) - Revised Score | The HVLT-Revised is a list learning task requiring the respondent to recall as many words as possible from a list of 12 words provided orally by the examiner. There is a learning trial, a delayed recall trial, and a recognition trial. Results show HVLT Total recall (Total number if words recalled over 3 trials) and HVLT Delayed recall (Total number of words recalled after 25 minute delay). | Baseline, T1 (13-15 weeks post baseline), T2 (28-30 weeks post baseline), T3 ( 56-58 weeks post baseline) | 
| Brief Visual Memory Test - Revised (BVMT-R) Score | The Brief Visual Memory Test is a performance based test that requires that participants reproduce simple visual images from memory (the images are displayed for 10 seconds then removed from view). The BVMT-R contains a learning trial, a recall trial, a recognition trial, and a copy trial. Each figure recalled is given 0,1, or 2 points based on accuracy and location recall. Results show BVMT Total recall (Total number if figures recalled over 3 trials: range 0 - 36) and BVMT delayed recall (total number of figures recalled after 25 min delay. Score range 0-12). Higher score correlate with better outcome. | Baseline, T1 (13-15 weeks post baseline), T2 (28-30 weeks post baseline), T3 ( 56-58 weeks post baseline) | 
| Grooved Pegboard Test Score | The Grooved Pegboard Test requires the placing of grooved pegs into a same-shaped hole as quickly as possible, once with the dominant hand and once with the non-dominant hand. | Baseline, T1 (13-15 weeks post baseline), T2 (28-30 weeks post baseline), T3 ( 56-58 weeks post baseline) | 
| Finger Tapping Test Score | The finger tapping test a fine motor speed requires tapping a lever with the index finger as quickly as possible. Trials with the dominant and non-dominant hand are completed. | Baseline, T1 (13-15 weeks post baseline), T2 (28-30 weeks post baseline), T3 ( 56-58 weeks post baseline) | 
| Coding Test Score | The coding test requires writing the corresponding symbol associated with a letter from a key provided. As many responses as possible are completed in the 120 second time limit. Results presented are the total number of correct responses (possible score range 0-135). | Baseline, T1 (13-15 weeks post baseline), T2 (28-30 weeks post baseline), T3 ( 56-58 weeks post baseline) | 
| Digit Span Test Score | The digit span test is a performance based test that requires repeating an increasing span of digits that are provided verbally by the examiner. The test includes trials of repeating digits in the same order presented by the examiner, in the reverse order of that presented by the examiner, and in ascending sequence. Scores range from 0 to 48. Higher score correlates with better outcome. | Baseline, T1 (13-15 weeks post baseline), T2 (28-30 weeks post baseline), T3 ( 56-58 weeks post baseline) | 
| Symbol Span Test Score | The subtest assesses visual working memory using novel visual stimuli. A series of abstract symbols on a page are shown briefly. Then the symbols are to be selected from an array of symbols in the same order they were presented on the previous page. This performance based test measures storage and manipulation of visual details in working memory. Score range from 0-36. Higher score correlates with better outcome. | Baseline, 3 months, 6 months and 12 months Post Intervention | 
| Instrumental Activities of Daily Living (IADL) Test Score | The Instrumental Activities of Daily Living (IADL) Test is a self-report measure assessing the amount of assistance, if any, required to do day-to-day tasks necessary to live independently. A summary score ranges from 0 (low function, dependent) to 8 (high function, independent) for women and 0 through 5 for men to avoid potential gender bias). Higher scores indicate worse performance in instrumental activities activities of daily living. | Baseline, T1 (13-15 weeks post baseline), T2 (28-30 weeks post baseline), T3 (56-58 weeks post baseline) | 
| NIH Toolbox | Computerized cognitive tests developed and distributed by the NIH. Tests include Pattern Comparison Processing Speed Test, Picture Vocabulary Test, Reading Recognition Test, Dimensional Change Card Sort Test, Flanker Inhibitory Control and Attention Test, Picture Sequence Memory Test, List Sorting Working Memory Test, and Oral Symbol Digit Test | Baseline, Post Intervention (Up to 58 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Soluble Cluster of Differentiation 14 (sCD14) Level | Soluble Cluster of Differentiation 14 (sCD14) is a marker of monocyte activation, is associated with neurocognitive impairment and HIV-associated neurocognitive disorders (HANDs) and higher mortality in persons living with HIV. | Baseline, T1 (13-15 weeks), T2 (28-30 weeks), T3 (56 -58 weeks) | 
| Interleukin 6 (IL-6) Level | IL-6 is a pro-inflammatory cytokine known to contribute to the pathogenesis of risk of cardiovascular disease (CVD) and cognitive impairment (CI) through inflammation and promotion of endothelial vascular dysfunction. IL-6 is measured by enzyme-linked immunosorbent assay (ELISA) and reported as in picograms per deciliter (pg/dL). Higher concentrations of IL-6 raise congenital heart defect risk. | Baseline, T1 (13-15 Weeks), T2 (28-30 weeks), T3 (56-58 weeks) | 
| Tumor Necrosis Factor Alpha (TNF-alpha) Level | TNFR1 membrane bound receptors that have been shown to bind TNF alpha. Activation of TNFR1 mediates the proinflammatory properties of TNF alpha. | Baseline, T1 (13-15 wks), T2 (28-30 wks), T3 (56-58 wks) | 
| Brain-derived Neurotrophic Factor (BDNF) Level | BDNF is a protein that occurs naturally in the hippocampus, cortex, and basal forebrain-areas vital to learning, memory, and higher thinking; an increase in BDNF in animal models and humans is thought to enhance neurogenesis. BDNF is reported as in picogram per milliliter (pg/mL). | Baseline, Post Intervention (Up to 58 weeks) | 
| Flow-Mediated Dilatation (FMD) | Flow-mediated dilatation (FMD) is a measure of endothelial function; the measure of % FMD at 60 seconds reflects arterial relaxation time after cuff deflation. | Baseline, T2 (28-30 weeks post baseline) |