Improving Physical Ability and Cellular Senescence Elimination in HIV

Phase 2RecruitingNCT07144293

National Institute of Allergy and Infectious Diseases (NIAID)80 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

HIV Frailty Prefrail

Eligibility

Sex: ALLMin age: 50 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Occurrence of Grade 2 or higher adverse events (AEs) after initiation of study treatment.

Time frame: 24 weeks

Occurrence of premature treatment discontinuations.

Time frame: 24 weeks

Absolute change in gait speed on 4-meter walk.

Time frame: From Week 0 to Week 12

Secondary Outcomes

Absolute change in time to complete 5 chair stands.

Time frame: From Week 0 to Week 12

Absolute change in Short Performance Physical Battery (SPPB) Total Balance Test score.

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.

Time frame: From Week 0 to Week 12

Absolute change in the SPPB score.

The SPPB scores range from a minimum of 0 to a maximum of 12. Higher scores indicate better physical performance.

Time frame: From Week 0 to Week 12

Absolute change in 4-meter gait speed.

Time frame: From Week 0 to Week 24

Absolute change in SPPB total balance test score.

The SPPB Total Balance Test scores range from a minimum of 0 to a maximum of 4. Higher scores indicate better balance performance.

Time frame: From Week 0 to Week 24

Absolute change in SPPB score.

The SPPB scores range from a minimum of 0 to a maximum of 12. Higher scores indicate better physical performance.

Time frame: From Week 0 to Week 24

Absolute change in timed chair stands.

Time frame: From Week 0 to Week 24

Absolute change in plasma senescence-associated secretory phenotype (SASP) biomarkers.