Aging, Biological, HIV, Inflammation, Obesity
Conditions
Keywords
Frail Elderly, IGF-1
Brief summary
The primary objective of this proposal is to compare a moderate or high intensity exercise intervention to improve physical function in persons aging with Human Immunodeficiency Virus (HIV).
Detailed description
The primary objective of this proposal is to compare a moderate or high intensity exercise intervention to improve physical function in persons aging with HIV. Both HIV-infected and HIV-uninfected older adults will be assigned to a moderate intensity cardiovascular and resistance training intervention for 12 weeks, and then randomized to either continue moderate intensity exercise, or increase to high intensity exercise for an additional 12 weeks. The primary outcome is the impact of exercise on physical function, as measured by the overall score of a modified Short Physical Performance Battery (mSPPB) and the chair rise time from the mSPPB. The secondary outcomes include changes in insulin-like growth factor-1 (systemic and local) and inflammation (interleukin-6 (IL-6), soluble tumor necrosis factor receptors 1 and 2 (sTNFR-1 and sTNFR-2)).
Interventions
OTHERHigh-intensity cardiovascular and resistance exercise
OTHERModerate-intensity cardiovascular and resistance exercise
Sponsors
National Institute on Aging (NIA)
Gilead Sciences
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Ages 50-75 * HIV+ must be on ART for a minimum of 2 years with viral load \<200 copies/mL * Sedentary * cluster of differentiation 4 (CD4) T-cell count \>200 cells/microliter * BMI \>19 and \<41 * Among females, must be post-menopausal * Able to perform activities of daily living with out assistance
Exclusion criteria
* Diabetes, poorly controlled with HgbA1c \>7.5; on insulin * On growth hormone (or growth hormone axis) therapy, intramuscular testosterone, corticosteroids. * Known active hepatitis B or C (viremia). * Severe liver disease * Uncontrolled hypertension (SPB \>180 or diastolic \>100). * Underlying cardiac conditions that would make exercise or exercise testing potentially unsafe (unstable ischemic heart disease, Class III or IV heart failure clinically significant aortic stenosis, uncontrolled angina, or uncontrolled arrhythmia) * pulmonary disease requiring the use of supplemental oxygen ≥ 4 liters with physical exertion * current diagnosis of malignancy (excluding non-melanoma skin cancers) within 48 weeks prior to enrollment * surgery/trauma/injury/fracture within 24 weeks prior to enrollment that may impact a subject's ability to exercise * history of stroke with residual deficits that may impact ability to exercise; orthopedic problems (e.g., severe osteoarthritis, rheumatoid arthritis) that greatly limit the ability to perform moderate-intensity resistance exercise (e.g., unable to be properly positioned in exercise equipment or to have severely restricted range of motion even after modifications have been made) * weight over 300 pounds * Montreal Cognitive Assessment (MOCA) score \< 18 (will be evaluated at screening visit after consent obtained) * AIDS-defining opportunistic infection within the 24 weeks prior to enrollment * Person who appear to have unstable health, are incapable of safely participating in the exercise intervention, or are felt to have a life expectancy of \< 1 year. * Participants on anticoagulants (clopidogrel, Coumadin, etc) will be excluded from the muscle biopsy. * Aspirin and Non-steroidal anti-inflammatory agents are not exclusions but should be stopped 1 week prior to muscle biopsy (subset of subjects).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Rise From a Chair 10 Times (Modified From the Original Short Physical Performance Battery) | 24 weeks | Chair rise time is measured as a continuous variable of time to stand up from a sitting position 10 times. Lower number = faster; larger number = slower |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Insulin-like Growth Factor (IGF)-1 | 24 weeks | Measures at baseline and following 24 weeks of exercise |
| Changes in Inflammation (Interleukin-6 [IL-6], Soluble Tumor Necrosis Factor Receptors 1 and TNF-alpha. | Baseline and 24 weeks | The primary outcome is change from 0 to 24 weeks. These changes in inflammation are measured at baseline (pre-exercise) and at 24 weeks (post exercise). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| HIV-Uninfected Controls All participants were aged 50 to 75 years, sedentary (\<60 minutes of physical activity each week for 6 months preceding by self-report), had a body mass index (BMI) between 20 and 40 kg/m2, and had no contraindications to initiating an exercise regimen (e.g., severe mobility limitation, unstable angina, supplemental oxygen requirement, uncontrolled hypertension). Participants with diabetes had hemoglobin A1c of 7.5% or less; sex hormone supplementation was restricted to stable, physiologic doses for ≥3 months prior to study entry and intramuscular testosterone was excluded. PLWH were on stable ART with an undetectable HIV-1 RNA for \>2 years and a CD4 T-cell count \>200 cells/µL.
At week 12, VO2 max measurements were repeated and participants were randomized to either continue moderate-intensity exercise (40-50% VO2 max and 60-70% 1-RM) or advance to high-intensity (60-70% of week 13 VO2 max and \>80% 1-RM) for the remaining 12 weeks. | 37 |
| Participants With HIV All participants were aged 50 to 75 years, sedentary (\<60 minutes of physical activity each week for 6 months preceding by self-report), had a body mass index (BMI) between 20 and 40 kg/m2, and had no contraindications to initiating an exercise regimen (e.g., severe mobility limitation, unstable angina, supplemental oxygen requirement, uncontrolled hypertension). Participants with diabetes had hemoglobin A1c of 7.5% or less; sex hormone supplementation was restricted to stable, physiologic doses for ≥3 months prior to study entry and intramuscular testosterone was excluded. PLWH were on stable ART with an undetectable HIV-1 RNA for \>2 years and a CD4 T-cell count \>200 cells/µL.
At week 12, VO2 max measurements were repeated and participants were randomized to either continue moderate-intensity exercise (40-50% VO2 max and 60-70% 1-RM) advance to high-intensity (60-70% of week 13 VO2 max and \>80% 1-RM) for the remaining 12 weeks. | 32 |
| Total | 69 |
Baseline characteristics
| Characteristic | Total | HIV-Uninfected Controls | Participants With HIV |
|---|---|---|---|
| Age, Continuous | 57.8 years STANDARD_DEVIATION 6.4 | 58.7 years STANDARD_DEVIATION 6.9 | 56.8 years STANDARD_DEVIATION 5.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 4 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 61 Participants | 33 Participants | 28 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 | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 3 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 51 Participants | 31 Participants | 20 Participants |
| Sex: Female, Male Female | 6 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 63 Participants | 35 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 37 | 0 / 32 |
| other Total, other adverse events | 9 / 37 | 17 / 32 |
| serious Total, serious adverse events | 0 / 37 | 0 / 32 |
Outcome results
Primary
Time to Rise From a Chair 10 Times (Modified From the Original Short Physical Performance Battery)
Chair rise time is measured as a continuous variable of time to stand up from a sitting position 10 times. Lower number = faster; larger number = slower
Time frame: 24 weeks
Population: 37 and 32 had baseline values; 29 and 27 (uninfected and with HIV, respectively) completed 24 weeks.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| HIV-uninfected Controls | Time to Rise From a Chair 10 Times (Modified From the Original Short Physical Performance Battery) | Change 0-12 weeks | -20 percentage change |
| HIV-uninfected Controls | Time to Rise From a Chair 10 Times (Modified From the Original Short Physical Performance Battery) | Change 13-24 weeks | -8 percentage change |
| Participants With HIV | Time to Rise From a Chair 10 Times (Modified From the Original Short Physical Performance Battery) | Change 0-12 weeks | -20 percentage change |
| Participants With HIV | Time to Rise From a Chair 10 Times (Modified From the Original Short Physical Performance Battery) | Change 13-24 weeks | -10 percentage change |
Secondary
Changes in Inflammation (Interleukin-6 [IL-6], Soluble Tumor Necrosis Factor Receptors 1 and TNF-alpha.
The primary outcome is change from 0 to 24 weeks. These changes in inflammation are measured at baseline (pre-exercise) and at 24 weeks (post exercise).
Time frame: Baseline and 24 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| HIV-uninfected Controls | Changes in Inflammation (Interleukin-6 [IL-6], Soluble Tumor Necrosis Factor Receptors 1 and TNF-alpha. | Change in IL-6 | -2 percentage of change |
| HIV-uninfected Controls | Changes in Inflammation (Interleukin-6 [IL-6], Soluble Tumor Necrosis Factor Receptors 1 and TNF-alpha. | Change in sTNFr1 | 2.3 percentage of change |
| HIV-uninfected Controls | Changes in Inflammation (Interleukin-6 [IL-6], Soluble Tumor Necrosis Factor Receptors 1 and TNF-alpha. | Change in TNFalpha | 1.3 percentage of change |
| Participants With HIV | Changes in Inflammation (Interleukin-6 [IL-6], Soluble Tumor Necrosis Factor Receptors 1 and TNF-alpha. | Change in IL-6 | 10 percentage of change |
| Participants With HIV | Changes in Inflammation (Interleukin-6 [IL-6], Soluble Tumor Necrosis Factor Receptors 1 and TNF-alpha. | Change in sTNFr1 | -2.5 percentage of change |
| Participants With HIV | Changes in Inflammation (Interleukin-6 [IL-6], Soluble Tumor Necrosis Factor Receptors 1 and TNF-alpha. | Change in TNFalpha | -2.5 percentage of change |
Secondary
Changes in Insulin-like Growth Factor (IGF)-1
Measures at baseline and following 24 weeks of exercise
Time frame: 24 weeks
Population: Missing data on one participant with HIV that completed the study. Data listed below ONLY includes data on persons with measurements at both baseline and week 24.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| HIV-uninfected Controls | Changes in Insulin-like Growth Factor (IGF)-1 | Baseline | 79.87 IGF-1 (ng/mL) |
| HIV-uninfected Controls | Changes in Insulin-like Growth Factor (IGF)-1 | Week 24 | 85.42 IGF-1 (ng/mL) |
| Participants With HIV | Changes in Insulin-like Growth Factor (IGF)-1 | Baseline | 86.4 IGF-1 (ng/mL) |
| Participants With HIV | Changes in Insulin-like Growth Factor (IGF)-1 | Week 24 | 84.65 IGF-1 (ng/mL) |