PREPARE (A5361s) Substudy of REPRIEVE (A5332)

HIV-1 Infection Clinical Trial

— PREPARE  

Official title:

Pitavastatin to REduce Physical Function Impairment and FRailty in HIV (PREPARE)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03070223
• Other study ID #: ACTG A5361s
• Secondary ID: UM1AI068636
• Status: Completed
• Start date: February 28, 2017
• Est. completion date: August 21, 2023

Study information

• Verified date: August 2023
• Source: AIDS Clinical Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Aging with HIV may be related to an earlier development of frailty (weakness) or disability, including difficulties in tests of strength or walking speed. Few treatments have been shown to prevent or slow these impairments in people with or without HIV. Some studies have suggested that the class of drugs called statins (for example, pitavastatin) might be helpful in slowing frailty or disability. This might happen by decreasing fat within the muscle or by decreasing inflammation markers (substances in the blood that determine how the body reacts to infection or irritation) in the blood. Other studies have shown that statins increase the risk of muscle aches and pains. This substudy is being done to determine the impact of the drug pitavastatin on muscle.

Description:

A5361s is a prospective study to determine the effects of pitavastatin on physical function. The study will enroll participants enrolled in both REPRIEVE (A5332) and its mechanistic sub-study A5333s or in REPRIEVE (A5332) alone and follow them for 48 months after entry to REPRIEVE (A5332). Treatment groups (pitavastatin vs placebo) will be defined according to randomization in REPRIEVE (A5332). No intervention will be provided in this sub-study.

Study visits are scheduled at PREPARE (A5361s) entry and at months 12, 24, 36 and 48 after REPRIEVE (A5332) entry. Each study visit will include evaluation of physical function, frailty and self-reported physical activity and sedentary time. In addition, demographic and clinical data, laboratory specimens and CT scans collected as part of the main study REPRIEVE (A5332) or its mechanistic sub-study A5333s will be used.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 602
• Est. completion date: August 21, 2023
• Est. primary completion date: August 21, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

Inclusion Criteria:

• Ambulatory participants enrolled in both REPRIEVE (A5332) and its Mechanistic Substudy (A5333s) or ambulatory participants who are newly enrolling into REPRIEVE (A5332) at A5333s ACTG sites.

Exclusion Criteria:

• Inability to ambulate independently (use of a cane or a walker is permitted) or rise from a chair without assistance.

Related Conditions & MeSH terms

• HIV-1 Infection

Intervention

Drug:
• Pitavastatin
One tablet (4 mg) taken once daily, orally with or without food
• Placebos
One tablet taken once daily, orally with or without food

Locations

Country	Name	City	State
Puerto Rico	Puerto Rico-AIDS CRS (5401)	San Juan
United States	The Ponce de Leon Ctr. CRS (5802)	Atlanta	Georgia
United States	University of Colorado Hospital CRS (6101)	Aurora	Colorado
United States	201 Johns Hopkins University CRS	Baltimore	Maryland
United States	31788 Alabama CRS	Birmingham	Alabama
United States	101 Massachusetts General Hospital (MGH) CRS	Boston	Massachusetts
United States	107 Brigham and Women's Hosp. ACTG CRS	Boston	Massachusetts
United States	Unc Aids Crs (3201)	Chapel Hill	North Carolina
United States	Northwestern University CRS (2701)	Chicago	Illinois
United States	Rush Univ. Med. Ctr. ACTG CRS (2702)	Chicago	Illinois
United States	Univ. of Cincinnati CRS (2401)	Cincinnati	Ohio
United States	Case CRS (2501)	Cleveland	Ohio
United States	The Ohio State Univ. AIDS CRS (2301)	Columbus	Ohio
United States	31443 Trinity Health and Wellness Center CRS	Dallas	Texas
United States	3203 Greensboro CRS	Greensboro	North Carolina
United States	31473 Houston AIDS Research Team (HART) CRS	Houston	Texas
United States	601 University of California, Los Angeles CARE Center CRS	Los Angeles	California
United States	University of Southern California CRS (1201)	Los Angeles	California
United States	Univ. of Miami AIDS CRS (901)	Miami	Florida
United States	Vanderbilt Therapeutics CRS (3652)	Nashville	Tennessee
United States	7804 Weill Cornell Chelsea CRS	New York	New York
United States	Columbia Physicians and Surgeons CRS (30329)	New York	New York
United States	Weill Med. College of Cornell Univ., The Cornell CTU -Chelsea (7803)	New York	New York
United States	31786 New Jersey Medical School Clinical Research Center CRS	Newark	New Jersey
United States	Hosp. of the Univ. of Pennsylvania CRS (6201)	Philadelphia	Pennsylvania
United States	Pittsburgh CRS (1001)	Pittsburgh	Pennsylvania
United States	2951 The Miriam Hospital (TMH) ACTG CRS	Providence	Rhode Island
United States	31787 University of Rochester Adult HIV Therapeutic Strategies Network CRS	Rochester	New York
United States	Washington University CRS (2101)	Saint Louis	Missouri
United States	Ucsd, Avrc Crs (701)	San Diego	California
United States	Ucsf Aids Crs (801)	San Francisco	California
United States	University of Washington AIDS CRS (1401)	Seattle	Washington
United States	Harbor-UCLA Med. Ctr. CRS (603)	Torrance	California

Sponsors (3)

Lead Sponsor	Collaborator
AIDS Clinical Trials Group	National Institute of Allergy and Infectious Diseases (NIAID), National Institute on Aging (NIA)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of change in chair rise rate	Participants will be asked to perform 10 chair stands. Chair rise rate will be calculated as time to perform chair stands divided by the number of chair stands performed. . Repeated measures analysis will be used to model chair rise rate over time and estimate rate of change.	Baseline and months 12, 24, 36 and 48
Primary	Rate of change in Inflammatory Index Score (IIS)	The IIS score will be calculated as 1/3 log [interleukin-6 (IL-6)] + 2/3 log [soluble tumor necrosis factor receptor 1 (sTNFR-1)] using samples collected as part of the main study REPRIEVE (A5332).	Baseline and 12 months
Primary	Rate of change in paraspinal muscle density	Paraspinal muscle density will be measured in Hounsfield units (HU) from the CT scans performed as part of A5333s, the mechanistic sub-study of REPRIEVE (A5332).	Baseline and 24 months
Secondary	Physical function outcome measure: Grip strength	Participant's grip strength in the dominant hand measured by Jamar Hydraulic Hand Dynamometer.	Baseline and months 12, 24, 36 and 48
Secondary	Physical function outcome measure: Gait speed	Participant's gait speed evaluated by time to complete 4-meter walk.	Baseline and months 12, 24, 36 and 48
Secondary	Physical function outcome measure: Balance	Balance evaluated by participant's ability to hold one leg stand for 30 seconds.	Baseline and months 12, 24, 36 and 48
Secondary	Physical function outcome measure: Physical function deficit	Physical function deficit defined as composite Short Physical Performance Battery (SPPB, consisting of repeat chair stand, balance, grip strength and gait speed tests) score <=10.	Baseline and months 12, 24, 36 and 48
Secondary	Physical function outcome measure: Self-reported physical activity	Self-reported physical activity evaluated by the questionnaire "Rapid Eating and Activity Assessment for Patients" (REAP).	Baseline and months 12, 24, 36 and 48
Secondary	Mechanistic outcome measure: Serum concentrations of biomarkers	Select biomarkers including each individual biomarker of the IIS (IL-6, sTNFR-1) as well as other biomarkers implicated in the pathogenesis of physical function impairment or those that may mediate the effects of statins on systemic inflammation. The specific list of biomarkers of interest will be finalized closer to the time of analysis, incorporating the developments in the field over the next few years.	Baseline and month 12
Secondary	Mechanistic outcome measure: Shoulder muscle density	Shoulder muscle density measured in Hounsfield units (HU) from the CT scans performed as part of A5333s, the mechanistic sub-study of REPRIEVE (A5332).	Baseline and month 24
Secondary	Mechanistic outcome measure: Upper back muscle density	Upper back muscle density measured in Hounsfield units (HU) from the CT scans performed as part of A5333s, the mechanistic sub-study of REPRIEVE (A5332).	Baseline and month 24
Secondary	Mechanistic outcome measure: Paraspinal muscle volume	Paraspinal muscle volume (area) measured from the CT scans performed as part of A5333s, the mechanistic sub-study of REPRIEVE (A5332).	Baseline and month 24
Secondary	Mechanistic outcome measure: Trunk muscle volume	Trunk muscle volume (area) measured from the CT scans performed as part of A5333s, the mechanistic sub-study of REPRIEVE (A5332).	Baseline and month 24