Clinical trial NCT03070223: PREPARE (A5361s) Ancillary Study of REPRIEVE (A5332)
Official title: Pitavastatin to REduce Physical Function Impairment and FRailty in HIV (PREPARE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV-1 Infection
Lead sponsor: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
Sponsor class: NETWORK
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
name: National Institute on Aging (NIA)
First posted: 2017-03-03
Enrollment: 602
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants were randomized as part of REPRIEVE.
Primary purpose: PREVENTION

Brief summary: Aging with HIV is associated with earlier development of frailty (weakness) or disability, including loss of physical and muscle strength, and 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 ancillary study was done to determine the impact of the drug pitavastatin on physical and muscle function.

Detailed description: The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE (A5332), subsequently referred to as REPRIEVE; NCT02344290) was a prospective, randomized, placebo-controlled, multicenter phase III trial to evaluate pitavastatin as prevention for cardiovascular disease events among people with HIV. PREPARE (A5361s, subsequently referred to as PREPARE) was an ancillary study of REPRIEVE to determine the effects of pitavastatin on physical and muscle function. The study enrolled participants:

1. enrolled in both REPRIEVE and its Mechanistic Substudy (A5333s, subsequently referred to as Mechanistic Substudy) within 24 of their REPRIEVE enrollment
2. enrolled in REPRIEVE alone concurrently with their REPRIEVE enrollment.

The target sample size was 600 participants. The study was conducted at the REPRIEVE U.S. sites participating in the Mechanistic Substudy, and enrollment from the Mechanistic Substudy was prioritized to maximize the number of participants with computed tomography (CT) scan data performed as part of the Mechanistic Substudy.

Treatment groups (pitavastatin vs placebo) were defined according to randomization in REPRIEVE. Participants were enrolled into PREPARE blinded to their REPRIEVE treatment allocation. No intervention was provided in this ancillary study.

Originally the study duration was 48 months after participants' REPRIEVE entry. An additional visit was added at Month 60 due to missed in-person evaluations during the COVID-19 related restrictions in 2020 through early 2021.

Study visits were scheduled at PREPARE entry and at months 12, 24, 36, 48 and 60 after REPRIEVE entry. Each study visit included 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 or its Mechanistic Substudy were used.

Eligibility criteria: 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.

Primary outcomes:
measure: Physical Function: Rate of Change in Chair Rise Rate
timeFrame: Entry and months 12, 24, 36, 48, 60
measure: Mechanistic: Rate of Change in Inflammatory Index Score (IIS)
timeFrame: Baseline and 12 months
measure: Muscle Quality: Paraspinal Muscle Density
timeFrame: Baseline and 24 months
Secondary outcomes:
measure: Physical Function: Rate of Change in Gait Speed
timeFrame: Entry and months 12, 24, 36, 48 and 60.
measure: Physical Function: Rate of Change in Grip Strength
timeFrame: Entry and months 12, 24, 36, 48 and 60
measure: Physical Function: Rate of Change in Risk of Impairment According to Balance
timeFrame: Entry and months 12, 24, 36, 48, 60
measure: Physical Function: Rate of Change in Modified SPPB Score
timeFrame: Entry and months 12, 24, 36, 48 and 60
measure: Physical Function: Rate of Change in Risk of Impairment According to SPPB
timeFrame: Entry and months 12, 24, 36, 48, 60
measure: Physical Function: Impairment According to DASI
timeFrame: Baseline, month 24 and end of REPRIEVE (average at 5.6 years)
measure: Frailty Phenotype
timeFrame: Entry and months 12, 24, 36, 48, 60
measure: Physical Activity: Frequency of <30 Minutes of Physical Activity 3 or More Days a Week
timeFrame: Baseline and months 12, 24, 36, 48, 60
measure: Physical Activity: Frequency of Watching >2 Hours of TV or Videos a Day
timeFrame: Baseline and months 12, 24, 36, 48, 60
measure: Muscle Quality: Pectoral Muscle Density
timeFrame: Baseline and month 24
measure: Muscle Quality: Infraspinatus Muscle Density
timeFrame: Baseline and month 24
measure: Muscle Area: Paraspinal Muscle Area
timeFrame: Baseline and month 24
measure: Muscle Area: Pectoral Muscle Area
timeFrame: Baseline and month 24
measure: Muscle Area: Infraspinatus Muscle Area
timeFrame: Baseline and month 24
measure: Mechanistic: Serum Concentrations of Biomarkers
timeFrame: Baseline and month 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama CRS (31788)
state: Alabama
city: Los Angeles
country: United States
facility: University of Southern California (1201)
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles CARE Center CRS (601)
state: California
city: San Diego
country: United States
facility: Ucsd, Avrc Crs (701)
state: California
city: San Francisco
country: United States
facility: Ucsf Aids Crs (801)
state: California
city: Torrance
country: United States
facility: Harbor-UCLA Med. Ctr. CRS (603)
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital CRS (6101)
state: Colorado
city: Chicago
country: United States
facility: 2701 Northwestern University CRS
state: Illinois
city: Chicago
country: United States
facility: Rush Univ. Med. Ctr. ACTG CRS (2702)
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University CRS (201)
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital (MGH) CRS (101)
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hosp. ACTG CRS (107)
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University CRS (2101)
state: Missouri
city: Newark
country: United States
facility: New Jersey Medical School Clinical Research Center CRS (31786)
state: New Jersey
city: New York
country: United States
facility: Weill Cornell Chelsea CRS (7804)
state: New York
city: New York
country: United States
facility: Weill Med. College of Cornell Univ., The Cornell CTU -Chelsea (7803)
state: New York
city: New York
country: United States
facility: Columbia Physicians and Surgeons CRS (30329)
state: New York
city: Rochester
country: United States
facility: University of Rochester Adult HIV Therapeutic Strategies Network CRS (31787)
state: New York
city: Chapel Hill
country: United States
facility: Unc Aids Crs (3201)
state: North Carolina
city: Greensboro
country: United States
facility: Greensboro CRS (3203)
state: North Carolina
city: Cincinnati
country: United States
facility: Univ. of Cincinnati CRS (2401)
state: Ohio
city: Cleveland
country: United States
facility: Case CRS (2501)
state: Ohio
city: Columbus
country: United States
facility: The Ohio State Univ. AIDS CRS (2301)
state: Ohio
city: Philadelphia
country: United States
facility: Hosp. of the Univ. of Pennsylvania CRS (6201)
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Pittsburgh CRS (1001)
state: Pennsylvania
city: Providence
country: United States
facility: The Miriam Hospital (TMH) ACTG CRS (2951)
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt Therapeutics CRS (3652)
state: Tennessee
city: Dallas
country: United States
facility: Trinity Health and Wellness Center CRS (31443)
state: Texas
city: Houston
country: United States
facility: Houston AIDS Research Team (HART) CRS (31473)
state: Texas
city: Seattle
country: United States
facility: University of Washington AIDS CRS (1401)
state: Washington
city: San Juan
country: Puerto Rico
facility: Puerto Rico-AIDS CRS (5401)
Study officials:
affiliation: Johns Hopkins University
name: Todd Brown, MD, PhD
role: STUDY_CHAIR
affiliation: University of Colorado, Denver
name: Kristine Erlandson, MD
role: STUDY_CHAIR
References:
citation: Erlandson KM, Umbleja T, Lu MT, Taron J, Ribaudo HJ, Overton ET, Presti RM, Haas DW, Sax PE, Yin MT, Zhai BK, Louis R, Upadhyay N, Eslami P, Douglas PS, Zanni MV, Fitch KV, Fulda ES, Fichtenbaum CJ, Malvestutto CD, Grinspoon SK, Brown TT. Associations of Muscle Density and Area With Coronary Artery Plaque and Physical Function. J Acquir Immune Defic Syndr. 2023 Oct 1;94(2):174-184. doi: 10.1097/QAI.0000000000003244.
citation: Abidi MZ, Umbleja T, Overton ET, Burdo T, Flynn JM, Lu MT, Taron J, Schnittman SR, Fitch KV, Zanni MV, Fichtenbaum CJ, Malvestutto C, Aberg JA, Fulda ES, Eckard AR, Manne-Goehler J, Tuan JJ, Ribaudo HJ, Douglas PS, Grinspoon SK, Brown TT, Erlandson KM. Cytomegalovirus IgG is Associated With Physical Function But Not Muscle Density in People With HIV. J Acquir Immune Defic Syndr. 2024 Apr 15;95(5):470-478. doi: 10.1097/QAI.0000000000003377.
citation: Umbleja T, Brown TT, Overton ET, Ribaudo HJ, Schrack JA, Fitch KV, Douglas PS, Grinspoon SK, Henn S, Arduino RC, Rodriguez B, Benson CA, Erlandson KM. Physical Function Impairment and Frailty in Middle-Aged People Living With Human Immunodeficiency Virus in the REPRIEVE Trial Ancillary Study PREPARE. J Infect Dis. 2020 Jul 9;222(Suppl 1):S52-S62. doi: 10.1093/infdis/jiaa249.