HIV Infection
Conditions
Keywords
exercise training, video telehealth, DNA methylation, Aging, HIV
Brief summary
Most Veterans living with HIV are 50 years of age or older and can expect to live more than 20 years longer with HIV medication. However, despite this success, Veterans living with HIV are more likely to have age-related diseases and loss of fitness and muscle that place them at increased risk for disability. This is a major priority for the VHA, the largest provider of HIV care in the United States. The goal of this study is to test a circuit exercise program in Veterans living with HIV that is designed to slowdown the aging process. The exercise program will be widely available by Video Teleconferencing (VTEL) and does not require stationary exercise equipment, making it widely accessible. This research will help reach the goal for Veterans to preserve their quality of life and ability to function independently. Novel findings will strengthen strategies to maintain life-long fitness through a personalized exercise prescription.
Detailed description
The Veterans Health Administration (VHA) is the largest U.S. HIV health provider with 64% of these Veterans 50+ years of age. HIV infection in the setting of antiretroviral therapy represents a chronic disease with an advanced aging phenotype manifested as increased cardiovascular disease, sarcopenia, and frailty, primarily driven by systemic inflammation. The investigators found a 42% reduction in VO2peak in older HIV+ adults that significantly improved with high-intensity aerobic (AEX) and resistance training (RT). Yet, durable strategies for high-intensity exercise in older adults remain a challenge and limited data are available in older HIV+ adults. There is an urgent need to address these knowledge gaps in order to prevent widespread disability in HIV+ Veterans. The objective is to provide a high-intensity exercise program for older Veterans that can be widely disseminated and attenuates processes underlying aging. Epigenetic changes with increased age encapsulate the putative effects of biological aging and lifestyle factors. DNA methylation (DNAm) patterns are frequently modified in genes encoding pro-inflammatory cytokines, but can be reversed with exercise training. DNA methylation age (DNAm Age) is an epigenetic biomarker that is expressed in years and provides a concrete benchmark of advanced aging. The investigators found that HIV+ adults have DNAm Age 11 years greater than age-matched adults without HIV. Further, in adults without HIV, increased DNAm Age is associated with physical inactivity, weakness and frailty. Preliminary data in the Veterans Aging Cohort Study (VACS) show that DNAm Age correlates with the VACS Index, a measure of frailty in HIV+ adults. However, the impact of exercise training on DNAm Age has yet to be determined in any patient population. The investigators propose to adapt center-based high-intensity AEX+RT intervention in older HIV+ Veterans into a video telehealth (VTEL) delivered functional (no stationary equipment) exercise program that leverages epigenetic outcomes to demonstrate anti-aging effects of exercise. The overarching hypothesis is that VTEL high-intensity functional circuit exercise in older HIV+ Veterans will improve the advanced aging phenotype and attenuate DNAm epigenetic processes underlying aging. Experimental approach includes a 12-week VTEL exercise intervention in 80 older HIV+ Veterans who are randomized to exercise or standard of care sedentary control groups. AIM 1 will determine the effect of VTEL exercise on VO2peak, sarcopenia, and frailty as phenotypic outcomes of advanced aging in HIV. AIM 2 will investigate the effect of VTEL exercise on DNAm Age as a biomarker of advanced aging. AIM 3 will determine the effect of VTEL exercise on DNA methylation of specific genes encoding specific pro-inflammatory cytokines in leukocytes. This approach will advance an understanding of effective and feasible exercise strategies to prevent and minimize disability in patient populations with advanced aging. Findings will provide an innovative approach to functional exercise in all older adults. DNAm Age could be used as a personalized benchmark for an individual's benefit from exercise to promote sustainable behavior change. Findings will also provide epigenetic risk profiles that can be used to generate a personalized exercise prescription, an important next step in the next decade of precision medicine. The proposal leverages exercise training experience in HIV and VTEL, availability of 3,000 HIV+ Veterans at Atlanta and Baltimore VAMCs, and the VHA VTEL infrastructure. The capacity to disseminate VTEL exercise with minimal cost using existing infrastructure will facilitate large-scale dissemination and national impact. Deliverables include improved clinical outcomes and substantial cost savings from reduced hospitalization and institutionalization rates.
Interventions
BEHAVIORALexercise training
12-weeks of high-intensity functional circuit exercise that will be broadcasted from the Salem VAMC to older Veterans living with HIV in the Atlanta and Baltimore VAMCs
Sponsors
VA Office of Research and Development
Atlanta VA Medical Center
Baltimore VA Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Caregiver, Outcomes Assessor)
Intervention model description
Exercise trial of 12-weeks high-intensity circuit exercise delivered by VTEL to older Veterans living with HIV that compares exercise group to standard of care sedentary control group
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Veteran living with HIV and under care at VAMC * 50 years of age and older * Stable antiretroviral therapy (same ARV medications within 3 months) * At least one HIV-1 PCR \< 20 c/ml (viral load) within prior 6 months
Exclusion criteria
* History of AIDS defining illnesses (within 6 months; CDC Criteria) * Myocardial infarction (within 3 months) * Exertional or unstable angina (current chest pain that limits activity) * Severe congestive heart failure (EF \< 20% in last year or NYHA Classification III or IV) * Uncontrolled hypertension (SBP \>180 \&/or DBP \> 110 mm Hg) * Therapy with beta blockers or non-dihydropyridine calcium channel blocker (within 1 month) * Screening EKG with ischemia, complex arrhythmia, or high-grade block (per Minnesota Code) * Poorly controlled DM within prior 1 month (FBS\>180 mg/dl, RBS \> 299 mg/dl, or HbA1C \> 10) * Receiving treatment for cancer except skin cancer (within 3 months) * Peripheral vascular disease with claudication * Severe arthritis limiting ambulation * Neurologic disease limiting ambulation (requiring assist device) * End stage liver disease (decompensated liver disease) * Chronic renal failure (requiring dialysis) * Severe pulmonary disease (home O2, admission for dyspnea or pneumonia within 1 month) * Use of systemic steroids (testosterone or glucocorticoids) or growth hormone (within 6 months) * Dementia (based on Evaluation to Consent) * Signs or symptoms of any medical comorbidity that would preclude exercise testing or training * Exercise on routine basis (structured aerobic exercise \> 3 times per week) within 1 month * Past medical history of COPD or emphysema AND mMRC score =4
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline VO2peak to After 12-week Exercise Intervention | baseline and 13-weeks | O2 consumption at peak exercise effort, VO2peak, is used as the standard measure of aerobic capacity in sedentary adults since the majority are not able to reach maximal aerobic capacity defined as a plateau in O2 consumption. VO2peak will be the average of the final 30 second values of O2 consumption at peak exercise on a treadmill using a modified Bruce protocol |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline DNA Methylation to After 12-week Exercise Intervention | baseline and 13-weeks | Epigenome-wide association studies (EWAS) |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORKris Ann K Oursler, MD
Salem VA Medical Center, Salem, VA
PRINCIPAL_INVESTIGATORVincent Marconi
Atlanta VA Medical and Rehab Center, Decatur, GA
PRINCIPAL_INVESTIGATORAlice S. Ryan, PhD
Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Exercise Group High-intensity circuit exercise training will be performed 3 times weekly for 12 weeks in a group setting. Circuit training is an exercise modality consisting of a series of exercises at different stations. Exercise training will be delivered by VTEL broadcast from the Salem VAMC to participants at the Atlanta VAMC and Baltimore VAMC. Rooms will be equipped with steps, hand and ankle weights, dumbbells, chairs and bands. No stationary exercise equipment will be used in either AEX or RT.
exercise training: 12-weeks of high-intensity functional circuit exercise that will be broadcasted from the Salem VAMC to older Veterans living with HIV in the Atlanta and Baltimore VAMCs | 45 |
| Control Group Sedentary activity (confirmed at eligibility no more than 1 structured physical activity/week) will be continued in participants randomized to the control group. Participants have the option after 12-week intervention phase to enter delayed exercise training to assure that all participants can receive exercise training. | 44 |
| Total | 89 |
Baseline characteristics
| Characteristic | Exercise Group | Control Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 15 Participants | 17 Participants | 32 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants | 27 Participants | 57 Participants |
| Age, Continuous | 62.7 years STANDARD_DEVIATION 6.6 | 63.1 years STANDARD_DEVIATION 7.5 | 62.9 years STANDARD_DEVIATION 7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 44 Participants | 44 Participants | 88 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 39 Participants | 39 Participants | 78 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 5 Participants | 4 Participants | 9 Participants |
| Region of Enrollment United States | 45 Participants | 44 Participants | 89 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 43 Participants | 43 Participants | 86 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 45 | 1 / 44 |
| other Total, other adverse events | 28 / 45 | 0 / 44 |
| serious Total, serious adverse events | 1 / 45 | 2 / 44 |
Outcome results
Primary
Change From Baseline VO2peak to After 12-week Exercise Intervention
O2 consumption at peak exercise effort, VO2peak, is used as the standard measure of aerobic capacity in sedentary adults since the majority are not able to reach maximal aerobic capacity defined as a plateau in O2 consumption. VO2peak will be the average of the final 30 second values of O2 consumption at peak exercise on a treadmill using a modified Bruce protocol
Time frame: baseline and 13-weeks
Population: Only participants who completed 12-week follow up testing. Among completers, 2 were missing VO2 data at Follow Up; Baseline data was provided for these participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Exercise Group | Change From Baseline VO2peak to After 12-week Exercise Intervention | Baseline | 1.99 Liters/minute | Standard Deviation 0.46 |
| Exercise Group | Change From Baseline VO2peak to After 12-week Exercise Intervention | 12 Week Follow Up | 2.07 Liters/minute | Standard Deviation 0.53 |
| Exercise Group | Change From Baseline VO2peak to After 12-week Exercise Intervention | Change | 0.09 Liters/minute | Standard Deviation 0.23 |
| Control Group | Change From Baseline VO2peak to After 12-week Exercise Intervention | Baseline | 2.05 Liters/minute | Standard Deviation 0.57 |
| Control Group | Change From Baseline VO2peak to After 12-week Exercise Intervention | 12 Week Follow Up | 2.07 Liters/minute | Standard Deviation 0.47 |
| Control Group | Change From Baseline VO2peak to After 12-week Exercise Intervention | Change | 0.00 Liters/minute | Standard Deviation 0.29 |
Secondary
Change From Baseline DNA Methylation to After 12-week Exercise Intervention
Epigenome-wide association studies (EWAS)
Time frame: baseline and 13-weeks
Other Pre-specified
VTEL Exercise Training Feasibility
Rates will be calculated for enrollment, attendance, and retention
Time frame: through study completion, an average of 1 year