Aging Problems, Frailty, HIV, Prefrail
Conditions
Keywords
Frailty, Prefrail, Physical Function, Aging, Senescence, Senolytic therapy
Brief summary
This clinical trial is a Phase II study designed to test the safety and effectiveness of a combination of dasatinib and quercetin (D+Q) in improving physical function for people with HIV who are frail or prefrail. The study will involve 80 participants, all aged 50 or older, who have been living with HIV for at least 10 years determined to meet criteria for diagnosis of frail or prefrail and are currently on a stable antiretroviral therapy with viral suppression. Participants will be randomly assigned to one of two groups: one group will receive the D+Q treatment, and the other will receive a placebo. The treatment will be given in six cycles over 12 weeks, with participants taking the medication for two days followed by 12 days without treatment. After the 12-week treatment period, participants will be monitored for another 12 weeks to assess the long-term effects. The study aims to determine if D+Q can improve physical function and other health outcomes in this population. Randomization will be stratified by sex and age to ensure balanced groups.
Interventions
DRUGDasatinib
Dasatinib will be administered as one 100 mg capsule.
DRUGQuercetin
Quercetin will be administered as five 250 mg capsules.
OTHERPlacebo - Dasatinib
Matching Placebo for Dasatinib will be administered as one 100 mg capsule.
OTHERPlacebo - Quercetin
Matching Placebo for Quercetin will be administered as five 250 mg capsules.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute on Aging (NIA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Must be an older person with confirmed diagnosis of HIV-1, defined as ≥ 50 years at study entry. 2. Must have been diagnosed with HIV at least 10 years ago, as confirmed by medical records or self-report. 3. Must be on a stable effective combination antiretroviral therapy (ART) regimen, with no changes in the regimen within 12 weeks before joining the study with 2 or more consecutive HIV-RNA levels \< 50 copies/mL within 48 weeks prior to study entry. 4. Must meet one or more Fried Frailty Phenotype criteria w/in 60 days prior to entry. 5. Must have eGFR \> 30 using CKD-EPI per 2021 calculation equation.
Exclusion criteria
1. Have used quercetin or dasatinib before. 2. Need to take medications that affect CYP3A4 or interact with dasatinib (e.g., certain HIV medications). 3. Have an active cancer (except non-melanoma skin cancer). 4. Have active liver disease with a Child Pugh score greater than 6, or other significant liver problems. 5. Are on dialysis or have had a kidney transplant. 6. Have had a heart attack, angina, stroke, or mini-stroke in the last 6 months. 7. Have a known history of pulmonary arterial hypertension or other respiratory disease requiring supplemental oxygen within 60 days before joining the study. 8. Have uncontrolled diabetes with an HgbA1c level greater than 8% within 60 days before joining the study. 9. Have substance use that might interfere with study participation, as determined by the site investigator. 10. Have had a significant illness within 60 days before joining the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Occurrence of Grade 2 or higher adverse events (AEs) after initiation of study treatment. | 24 weeks |
| Occurrence of premature treatment discontinuations. | 24 weeks |
| Absolute change in gait speed on 4-meter walk. | From Week 0 to Week 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute change in time to complete 5 chair stands. | From Week 0 to Week 12 | — |
| Absolute change in Short Performance Physical Battery (SPPB) Total Balance Test score. | From Week 0 to Week 12 | The Short Performance Physical Battery (SPPB) Total Balance Test scores range from a minimum of 0 to a maximum of 4. Higher scores indicate better balance performance. |
| Absolute change in the SPPB score. | From Week 0 to Week 12 | The SPPB scores range from a minimum of 0 to a maximum of 12. Higher scores indicate better physical performance. |
| Absolute change in 4-meter gait speed. | From Week 0 to Week 24 | — |
| Absolute change in SPPB total balance test score. | From Week 0 to Week 24 | The SPPB Total Balance Test scores range from a minimum of 0 to a maximum of 4. Higher scores indicate better balance performance. |
| Absolute change in SPPB score. | From Week 0 to Week 24 | The SPPB scores range from a minimum of 0 to a maximum of 12. Higher scores indicate better physical performance. |
| Absolute change in timed chair stands. | From Week 0 to Week 24 | — |
| Absolute change in plasma senescence-associated secretory phenotype (SASP) biomarkers. | From Week 0 to Weeks 12 and 24 | — |
| Absolute change in serum SASP biomarkers. | From Week 0 to Weeks 12 and 24 | — |
| Absolute change in cognitive function on the AIDS Clinical Trials Group (ACTG) Neuropsychology Battery "Neuropsychological Battery" section | From Week 0 to Weeks 12 and 24 | Higher scores indicate better cognitive performance. |
| Absolute change in symptoms of anxiety and depression using the Patient Health Questionnaire-9 (PHQ-9) assessments | From Week 0 to Weeks 12 and 24 | The PHQ-9 scores range from a minimum of 0 to a maximum of 27. Lower scores indicate better mental health, while higher scores indicate more severe depression. |
| Absolute change in Veterans Aging Cohort Study (VACS) Index 2.0. | From Week 0 to Weeks 12 and 24 | The VACS Index 2.0 scores range from a minimum of 0 to a maximum of 164. Higher scores indicate a higher risk of mortality and worse health outcomes. |
| Absolute change in participant-reported Quality of Life (QoL) on the Patient-Reported Outcomes Measurement Information System (PROMIS) QoL measure | From Week 0 to Weeks 12 and 24 | The PROMIS QoL measure have no fixed minimum score, but scores can theoretically go as low as 0 and no fixed maximum score, but scores can theoretically go as high as 100. Higher scores indicate better quality of life. |
Countries
United States
Outcome results
None listed