Losartan to Reduce Inflammation and Fibrosis Endpoints in HIV Trial

NCT ID: NCT02049307

Last Updated: 2019-12-10

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

108 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-10-16

Study Completion Date

2018-12-14

Brief Summary

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

Detailed Description

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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.

Conditions

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Inflammation Fibrosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Treatment

Losartan 100mg daily

Group Type ACTIVE_COMPARATOR

Losartan 100mg daily

Intervention Type DRUG

Placebo

Matching placebo

Group Type PLACEBO_COMPARATOR

Matching placebo

Intervention Type DRUG

Interventions

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Losartan 100mg daily

Intervention Type DRUG

Matching placebo

Intervention Type DRUG

Eligibility Criteria

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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)
Minimum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hennepin Healthcare Research Institute

OTHER

Sponsor Role lead

Responsible Party

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Jason Baker

Protocol Chair

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jason Baker, M.D.

Role: PRINCIPAL_INVESTIGATOR

Hennepin Healthcare Research Institute

Locations

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UCSF

San Francisco, California, United States

Site Status

NIH Clinical Center

Bethesda, Maryland, United States

Site Status

Allina Health

Minneapolis, Minnesota, United States

Site Status

Hennepin County Medical Center

Minneapolis, Minnesota, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 33252490 (View on PubMed)

Provided Documents

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Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

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PCC-007

Identifier Type: -

Identifier Source: org_study_id