PREPARE (A5361s) Substudy of REPRIEVE (A5332) (PREPARE)

• ClinicalTrials.gov Identifier: NCT03070223
• Recruitment Status: Active, not recruiting
• First Posted: March 3, 2017
• Last Update Posted: October 29, 2020
• Sponsor: AIDS Clinical Trials Group
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); National Institute on Aging (NIA)
• Information provided by (Responsible Party): AIDS Clinical Trials Group

Tracking Information

• First Submitted Date: February 22, 2017
• First Posted Date: March 3, 2017
• Last Update Posted Date: October 29, 2020
• Actual Study Start Date: February 28, 2017
• Estimated Primary Completion Date: March 24, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 2, 2017)

• Rate of change in chair rise rate [ Time Frame: Baseline and months 12, 24, 36 and 48 ]
  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.
• Rate of change in Inflammatory Index Score (IIS) [ Time Frame: Baseline and 12 months ]
  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).
• Rate of change in paraspinal muscle density [ Time Frame: Baseline and 24 months ]
  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).

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 2, 2017)

• Physical function outcome measure: Grip strength [ Time Frame: Baseline and months 12, 24, 36 and 48 ]
  Participant's grip strength in the dominant hand measured by Jamar Hydraulic Hand Dynamometer.
• Physical function outcome measure: Gait speed [ Time Frame: Baseline and months 12, 24, 36 and 48 ]
  Participant's gait speed evaluated by time to complete 4-meter walk.
• Physical function outcome measure: Balance [ Time Frame: Baseline and months 12, 24, 36 and 48 ]
  Balance evaluated by participant's ability to hold one leg stand for 30 seconds.
• Physical function outcome measure: Physical function deficit [ Time Frame: Baseline and months 12, 24, 36 and 48 ]
  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.
• Physical function outcome measure: Self-reported physical activity [ Time Frame: Baseline and months 12, 24, 36 and 48 ]
  Self-reported physical activity evaluated by the questionnaire "Rapid Eating and Activity Assessment for Patients" (REAP).
• Mechanistic outcome measure: Serum concentrations of biomarkers [ Time Frame: Baseline and month 12 ]
  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.
• Mechanistic outcome measure: Shoulder muscle density [ Time Frame: Baseline and month 24 ]
  Shoulder muscle density measured in Hounsfield units (HU) from the CT scans performed as part of A5333s, the mechanistic sub-study of REPRIEVE (A5332).
• Mechanistic outcome measure: Upper back muscle density [ Time Frame: Baseline and month 24 ]
  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).
• Mechanistic outcome measure: Paraspinal muscle volume [ Time Frame: Baseline and month 24 ]
  Paraspinal muscle volume (area) measured from the CT scans performed as part of A5333s, the mechanistic sub-study of REPRIEVE (A5332).
• Mechanistic outcome measure: Trunk muscle volume [ Time Frame: Baseline and month 24 ]
  Trunk muscle volume (area) measured from the CT scans performed as part of A5333s, the mechanistic sub-study of REPRIEVE (A5332).

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: PREPARE (A5361s) Substudy of REPRIEVE (A5332)
• Official Title: Pitavastatin to REduce Physical Function Impairment and FRailty in HIV (PREPARE)
• Brief 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.

Detailed 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.

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Probability Sample
• Study Population: It is desired that a substantial proportion of participants are enrolled in A5333s.
• Condition: HIV-1 Infection

Intervention

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

Study Groups/Cohorts

• Experimental: Pitavastatin
  Participants who receive pitavastatin in the main study REPRIEVE (A5332).
  Intervention: Drug: Pitavastatin
• Placebo Comparator: Placebo
  Participants who receive placebo for pitavastatin in the main study REPRIEVE (A5332).
  Intervention: Drug: Placebos

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: February 21, 2018): 602
• Original Estimated Enrollment (submitted: March 2, 2017): 600
• Estimated Study Completion Date: March 24, 2023
• Estimated Primary Completion Date: March 24, 2023 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Puerto Rico, United States

Administrative Information

• NCT Number: NCT03070223
• Other Study ID Numbers: ACTG A5361s; UM1AI068636 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: AIDS Clinical Trials Group
• Study Sponsor: AIDS Clinical Trials Group

Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)
• National Institute on Aging (NIA)

Investigators

• Study Chair: Todd Brown, MD, PhD; Johns Hopkins University
• Study Chair: Kristine Erlandson, MD; University of Colorado, Denver

• PRS Account: AIDS Clinical Trials Group
• Verification Date: June 2020