The Impact of Structured Exercise on Brain Health in HIV Positive Individuals

Study Overview
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Brief Summary
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Exercise programs that combine resistance exercise with aerobic training yield optimal health benefits for people with HIV. The global aim of this study is to contribute evidence for the impact potential of a comprehensive exercise program on brain health in people with HIV. This study is part of a larger project based upon a cohort multiple randomized controlled design. Within a fully characterized cohort which is followed over time, people meeting the specific criteria for an exercise intervention will be identified. The sample will be randomly selected to receive the intervention; the remaining eligible persons will serve as controls. The intervention group will receive a 45 minute structured exercise program 3 times a week consisting of aerobic exercise and resistance training for a total of 12 weeks.

Detailed Description
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Exercise is an inexpensive intervention with widespread benefits to vascular and musculoskeletal health and few harms. Showing an additional benefit to brain health and cognition in particular is likely to encourage adoption and help elucidate mechanisms underpinning brain health in HIV. The primary objective of the study is to estimate, in comparison to individuals not offered the exercise intervention, the extent to which a comprehensive exercise program impacts on indicators of brain health, where these indicators are the primary outcome of cognitive ability (B-CAM) and the related brain health outcomes of depression, anxiety, fatigue, motivation, and speed of motor performance. A secondary objective is to estimate the extent to which changes in brain health are mediated through exercise induced changes in brain network function as measured by EEG and/or by exercise induced changes in muscle power, aerobic capacity, physical function, and body composition.

Official Title
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The Impact of Structured Exercise on Brain Health in HIV Positive Individuals

Conditions
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HIV

Intervention / Treatment
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* Other: Exercise group


Participation Criteria
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Eligibility Criteria
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The exercise intervention will target individuals recruited from two Montreal clinics who identified at cohort entry they were interested in being approached for different trials if they eligible. Inclusion Criteria: men and women aged ≥ 35 years, HIV+ for at least 1 year, able to communicate adequately in either French or English, and able to give written informed consent. Also, participants must identify that they are mostly sedentary by reporting that they perform moderate level physical activity of 30 minutes duration less than twice a week or have limitations in performing vigorous activities, walking a kilometer, or climbing stairs. Individuals answering yes to any of the Physical Activities Readiness Questionnaire (PAR-Q) (Thomas et al., 1992) items except taking medication (Item 6) will require clearance from their physician to be included. Exclusion Criteria: people with dementia (MOCA < 18) or treating physician's concern about capacity to consent, life expectancy of < 3 years or other personal factors limiting the ability to participate in follow-up, non-HIV-related neurological disorder likely to affect cognition, known active CNS opportunistic infection or hepatitis C requiring interferon (IFN) treatment during the follow-up period, psychiatric disorder on the psychotic axis, current substance use disorder or severe substance use disorder within the past 12 months. Also excluded will be people with a contraindication for exercise from cardiovascular or musculoskeletal co-morbidity as gathered from the medical history and from the PAR-Q (Thomas et al., 1992).

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Male

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: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exercise group<br>The 45 minute exercise program will be performed 3 times a week and will consist of aerobic exercise and resistance training for 12 weeks. | Other: Exercise group<br>* Interval training will be performed for 21 minutes including a 3 minute warm-up and cool-down period. The interval program will be 15 minutes at 65-75% of maximal heart rate with 30 sec. bursts of exercise to 80-85%; intervals. Resistance training will be done as a circuit and will make use of weight machines and functional exercises. Resistance will be done in 2 sets of 15 repetitions and will last 24 minutes. The work load of the program is calibrated and is conducted at a specified rhythm. All exercise sessions will be supervised.<br>|
| No Intervention: Control<br>No treatment | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Cognitive Ability | The primary outcome is cognitive ability as measured by B-CAM. This is part of the measurement platform for all and the value taken at the regular assessment prior to the exercise intervention will serve as the baseline value and the subsequent evaluation 9 months following will serve as the follow-up value. The strategy ensures that the intervention cohort does not have additional measurements of cognitive ability than the control cohort. The items on the B-CAM fit the Rasch Model and as such have linearized units on a logit scale. | 0 and 39 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in depression | Measured by Hospital Anxiety and Depression Scale (HADS) | 0 and 39 weeks | 
| Change in depression | Measured by RAND -36 Mental Health Inventory (MHI) | 0 and 39 weeks | 
| Change in stress levels | Measured by Trier Inventory for Chronic Stress (TICS) | 0 and 39 weeks | 
| Change in anxiety | Measured by Hospital Anxiety and Depression Scale (HADS) | 0 and 39 weeks | 
| Change in fatigue | Measured by RAND-36 Vitality | 0 and 39 weeks | 
| Change in motivation | Measured by Motivation Ladder | 0 and 39 weeks | 
| Change in global quality of life (QOL) | Measured by Person Generated Index (PGI) | 0 and 39 weeks | 
| Change in health related quality of life (HRQoL) | Measured by RAND-36 | 0 and 39 weeks | 
| Change in health related quality of life (HRQoL) | Measured by WHOQOL-HIV | 0 and 39 weeks | 
| Change in measures of brain network function | The measures of brain network function are derived from event related potential (ERPs) which are electric potentials produced by the brain in response to auditory or visual stimulation, respectively. These brain responses are easily recorded noninvasively with scalp electrodes (EEG). ERPs allow insights into the neural mechanisms underlying specific cognitive processes. The potentials of interest here include the N1, N2, P2 and P3 ERPs. | 0 and 12 weeks | 
| Change in skeletal muscle mass | A total body Dual energy X-ray absorptiometry (DEXA) scan will be done to compute skeletal muscle mass (whole body, spine and thigh) (Lee & Gallagher, 2009). | 0 and 12 weeks | 
| Change in muscle quality | Peripheral quantitative computed tomography (pQCT) will be used to measure the muscle quality in lower extremity (MacIntyre & Lorbergs, 2012). | 0 and 12 weeks | 
| Change in exercise capacity | Measured by step test | 0 and 12 weeks | 
| Change in functional walking capacity | Measured by Six Minute Walk Test (6MWT) | 0 and 12 weeks | 
| Change in quadriceps power | Measured using leg press and jump test | 0 and 12 weeks | 
| Change in core strength | Measured using curl ups/push ups | 0 and 12 weeks | 
| Change in grip strength | Measured using hand dynamometer | 0 and 12 weeks | 
| Change in gait speed | Comfortable gait speed: GAITRite; Fast gait speed: GAITRite; Dual task gait speed: GAITRite and naming the fruits | 0 and 12 weeks | 
| Change in exercise enjoyment | Exercise enjoyment will be measured by Physical Activity Enjoyment Scale (PACES) (Mullen et al., 2011). | 0 and 12 weeks | 
| Change in physical activity | The data from the accelerometer will be used to estimate the extent to which the structured exercise program carries over into everyday life. Participants will be asked to wear an ActivPal accelerometer for 5-7 days prior to the start of the intervention, at 6 weeks, and after 12 weeks, to objectively measure habitual physical activity. | 0, 6 and 12 weeks | 
| Change in semantic fluency | Following question will be asked: Name as many animals as you can in 1 minute (in sitting). | 0 and 12 weeks |