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

Primary Purpose

Inflammation, Fibrosis

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Losartan 100mg daily

Matching placebo

About this trial

This is an interventional treatment trial for Inflammation

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

UCSF
NIH Clinical Center
Allina Health
Hennepin County Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Treatment

Placebo

Arm Description

Losartan 100mg daily

Matching placebo

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Change in CD4+ Cell Count From Baseline to 12 Months.

Change in cluster of differentiation 4 (CD4+) cell count from baseline to 12 months

Full Information

NCT ID

NCT02049307

First Posted

January 27, 2014

Last Updated

December 6, 2019

Sponsor

Hennepin Healthcare Research Institute

1. Study Identification

Unique Protocol Identification Number

NCT02049307

Brief Title

Losartan to Reduce Inflammation and Fibrosis Endpoints in HIV Trial

Acronym

LIFE-HIV

Official Title

Losartan to Reduce Inflammation and Fibrosis Endpoints in HIV Trial

Study Type

Interventional

2. Study Status

Record Verification Date

December 2019

Overall Recruitment Status

Completed

Study Start Date

October 16, 2014 (Actual)

Primary Completion Date

December 14, 2018 (Actual)

Study Completion Date

December 14, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Hennepin Healthcare Research Institute

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Inflammation, Fibrosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

108 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment

Arm Type

Active Comparator

Arm Description

Losartan 100mg daily

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Matching placebo

Intervention Type

Drug

Intervention Name(s)

Losartan 100mg daily

Intervention Type

Drug

Intervention Name(s)

Matching placebo

Primary Outcome Measure Information:

Title

Change in Interleukin 6 (IL-6) Plasma Levels From Baseline to 12 Months

Description

Difference between treatment and control IL-6 plasma levels from pre-treatment to on-treatment values

Time Frame

Baseline and 12 months

Secondary Outcome Measure Information:

Title

Change in CD4+ Cell Count From Baseline to 12 Months.

Description

Change in cluster of differentiation 4 (CD4+) cell count from baseline to 12 months

Time Frame

Baseline and 12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jason Baker, M.D.

Organizational Affiliation

Hennepin Healthcare Research Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

UCSF

City

San Francisco

State/Province

California

ZIP/Postal Code

94110

Country

United States

Facility Name

NIH Clinical Center

City

Bethesda

State/Province

Maryland

ZIP/Postal Code

20892

Country

United States

Facility Name

Allina Health

City

Minneapolis

State/Province

Minnesota

ZIP/Postal Code

55407

Country

United States

Facility Name

Hennepin County Medical Center

City

Minneapolis

State/Province

Minnesota

ZIP/Postal Code

55417

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

33252490

Citation

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.

Results Reference

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Losartan to Reduce Inflammation and Fibrosis Endpoints in HIV Trial

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