Losartan to Reduce Inflammation and Fibrosis Endpoints in HIV Trial (LIFE-HIV)

The purpose of this study is to evaluate the potential effectiveness of losartan (100mg daily) for reducing inflammation and improving immune recovery.

Study Overview

• Status: Completed
• Conditions: Fibrosis; Inflammation
• Intervention / Treatment: Drug: Matching placebo; Drug: Losartan 100mg daily

Detailed Description

Our general goal is to evaluate the potential effectiveness of losartan (100mg daily) for reducing inflammation and improving immune recovery, given the potential for these treatment effects to reduce risk for long-term non-AIDS-defining complications among older HIV positive participants. Prior to conducting a clinical outcome trial, candidate treatments must be studied among HIV positive patients given the unique pathogenesis driving inflammation and disease risk.

The potential benefits of losartan (100mg daily) will be studied among HIV positive individuals over age 50 years whose CD4 counts remain ≤600 cells/mm3. Participants (n=110, 55 per group) will be randomized to receive losartan or matching placebo daily. After randomization, participants will start losartan (or placebo) at a dose of 50mg once daily, increasing to 100mg once daily at the 2-week study visit pending results of a week 2 toxicity lab evaluation (see 2.4 below for criteria). Following month 1, participants will return for follow-up study visit procedures at months 3, 6, 9, and 12.

Changes from baseline in measures of inflammation, immune activation, immune recovery and fibrosis within lymphatic tissues will be studied. The primary outcome will be the average of IL-6 levels over 12 months, and the main secondary outcome will be change in CD4 count in blood over 12 months.

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94110
      • UCSF
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • NIH Clinical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Allina Health
    • Minneapolis, Minnesota, United States, 55417
      • Hennepin County Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• HIV infection (verified by previous positive antibody or detectable HIV RNA level)
• Age > 50 years
• Receiving continuous ART for >= 2 years (regimen changes > 6 months prior to enrollment are allowed)
• HIV RNA level < 200 copies/mL for >= 1 year (1 measure >= 200 allowed if also < 1000 and preceded and followed by values < 200 copies/mL)
• Blood CD4+ T-cell count < 600 cells/mm cubed
• Systolic blood pressure > 120 mmHg (mean value if >= 2 measures obtained)
• Estimated glomerular filtration rate (GFR )> 30 mL/min/1.73 m squared
• Do not anticipate starting or stopping statin or aspirin therapy during the study

Exclusion Criteria:

• Pregnancy or breastfeeding
• A contra-indication to taking an angiotensin receptor blocker (ARB) (e.g., cirrhosis, prior angioedema with angiotensin-converting enzyme inhibitor (ACE-I), or use of drug with potential drug-interaction [e.g., rifaximin])
• A clinical indication for ARB or ACE-I therapy (e.g., cardiovascular disease (CVD), stroke, or diabetes mellitus (DM))
• Current treatment with ARB or medication with overlapping mechanism (e.g., ACE-I or aldosterone antagonist)
• Current treatment with immunomodulatory drugs within the past 6 months
• Current hepatitis treatments (e.g., interferon, ribavirin) within the past 6 months
• Serum potassium > 5.0 millimoles per liter (mmol/L) within 3 months of entry
• Invasive cancer in the prior year or receiving cancer treatment (not including carcinoma-in-situ or basal cell cancer of the skin)
• Cirrhosis or end-stage liver disease
• Rheumatologic or chronic inflammatory disease (e.g., systematic lupus erythematous, psoriasis, rheumatoid arthritis, vasculitis, sarcoidosis, Crohn's disease)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Matching placebo	Drug: Matching placebo
ACTIVE_COMPARATOR: Treatment; Losartan 100mg daily	Drug: Losartan 100mg daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Interleukin 6 (IL-6) Plasma Levels From Baseline to 12 Months	Difference between treatment and control IL-6 plasma levels from pre-treatment to on-treatment values	Baseline and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in CD4+ Cell Count From Baseline to 12 Months.	Change in cluster of differentiation 4 (CD4+) cell count from baseline to 12 months	Baseline and 12 months

Collaborators and Investigators

• Sponsor: Hennepin Healthcare Research Institute

Publications and helpful links

General Publications

• Baker JV, Wolfson J, Collins G, Morse C, Rhame F, Liappis AP, Rizza S, Temesgen Z, Mystakelis H, Deeks S, Neaton J, Schacker T, Sereti I, Tracy RP. Losartan to reduce inflammation and fibrosis endpoints in HIV disease. AIDS. 2021 Mar 15;35(4):575-583. doi: 10.1097/QAD.0000000000002773.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 16, 2014
• Primary Completion (ACTUAL): December 14, 2018
• Study Completion (ACTUAL): December 14, 2018

Study Registration Dates

• First Submitted: January 27, 2014
• First Submitted That Met QC Criteria: January 29, 2014
• First Posted (ESTIMATE): January 30, 2014

Study Record Updates

• Last Update Posted (ACTUAL): December 10, 2019
• Last Update Submitted That Met QC Criteria: December 6, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Fibrosis; Inflammation; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Losartan
• Other Study ID Numbers: PCC-007