Telmisartan to Reduce AIDS-Related Fibrotic and Inflammatory Contributors (TRAFIC Study)

NCT01928927 | Completed Phase 2 Results DMC

• 2 other identifiers: ACTG A5317UM1AI068636
• Study Type: interventional
• Target: 58
• Locations: 2 countries
• Sites: 12

Brief Summary

The main goal of this study was to see if a drug called telmisartan would decrease fibrosis (scarring) and inflammation (irritation) in people who are infected with HIV and doing well on their HIV medications. The study was also done to see what effects telmisartan has on other signs of disease and inflammation in the body, and to see whether people who have HIV can take telmisartan safely and without side effects that make them want to stop the drug. Telmisartan is FDA-approved for treating high blood pressure and decreasing the chance of heart attacks and strokes in people over the age of 55 years of age who are at high risk for these events.

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (2)

• Change in Percent Collagen I Deposition on Lymph Node Pathology From Baseline to Week 48

  Percent collagen I deposition is defined as the average % collagen stained in multiple uniform sized high magnification images in each sample. Change was absolute change defined as the Week 48 value minus the baseline value.

  baseline and week 48

• Change in Percent Collagen I Deposition on Subcutaneous Abdominal Adipose Tissue Pathology From Baseline to Week 48

  Percent collagen I deposition defined as percentage of fibrotic/collagen area to total area. Change was absolute change defined as the Week 48 value minus the baseline value.

  baseline and week 48

Secondary Outcomes (64)

• Change in Percent Fibronectin Deposition on Lymph Node Pathology From Baseline to Week 48

  baseline and week 48

• Change in Percent Fibronectin Deposition on Subcutaneous Abdominal Adipose Tissue Pathology From Baseline to Week 48

  baseline and week 48

• Change in Percent Collagen VI Deposition on Subcutaneous Abdominal Adipose Tissue Pathology From Baseline to Week 48

  baseline and week 48

• Highest Grade Non-biopsy-related Adverse Event

  after baseline to week 48

• Change in IL-6 From Baseline to Week 4

  baseline and week 4

Study Arms (2)

Arm A: Telmisartan

EXPERIMENTAL

Drug: Telmisartan

Arm B: No Study Drug

NO INTERVENTION

Participants received no study drug and followed the week 0-48 evaluation schedule.

Interventions

Telmisartan DRUG

Participants received Telmisartan 40 mg daily during weeks 0-4 followed by telmisartan 80 mg daily during weeks 5-48.

Arm A: Telmisartan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to Step 1 entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, or plasma HIV-1 RNA viral load \>2000 copies/mL on two occasions.
• On antiretroviral therapy (ART) continuously for ≥48 weeks prior to Step 1 entry.
• Documentation of HIV-1 RNA \<50 copies/mL at screening, performed by any US laboratory that has a CLIA certification or its equivalent.
• At least one HIV-1 RNA level \<200 copies/mL in the 48 weeks prior to Step 1 entry (not including the screening).
• No change in ART regimen in the 12 weeks prior to Step 1 entry (except as noted below).
• NOTE: Modifications of ART dosing during the 12 weeks prior to Step 1 entry are permitted. In addition, the change in formulation (eg, from standard formulation to fixed dose combination or single tablet regimen) is allowed within 12 weeks of Step 1 entry. A within-class single drug substitution (eg, switch from nevirapine to efavirenz or from atazanavir to darunavir) is allowed within 12 weeks of Step 1 entry, with the exception of a switch from any other NRTI to abacavir. No other changes in ART in the 12 weeks prior to Step 1 entry are permitted.
• No active plan to change ART for the 48-week study duration.
• Body mass index (BMI) 20-35 kg/m\^2.
• For females of reproductive potential, negative serum or urine pregnancy test within 3 days prior to Step 1 entry.
• Ability and willingness of subject or legal guardian/representative to provide informed consent.
• Willingness to undergo the Step 1 entry and week 48 lymphoid and adipose tissue biopsies.
• Entry lymphoid tissue and adipose tissue specimen for assay of the primary endpoint has been obtained. (Prior to Letter of Amendment #2, 11/19/14)
• (Letter of Amendment #2, 11/19/14) Entry lymphoid tissue and adipose tissue specimens for assay of the primary endpoint have been obtained, entered into the ACTG's Laboratory Data Management System (LDMS), and confirmed by the protocol team as adequate for endpoint determination.
• NOTE: If the lymph node specimen is determined by the protocol team to be inadequate for endpoint determination despite the interventions summarized in LOA #2, the participant will be permitted to enroll if adequate adipose tissue is obtained. However, as change in lymph node fibrosis remains one of the primary endpoints of this study, it is critical that every effort be made to obtain an adequate sample while still trying to minimize complication rates.
• Willingness to undergo the week 48 lymphoid and adipose tissue biopsies. (Prior to Letter of Amendment #2, 11/19/14)

You may not qualify if:

• More than one HIV-1 RNA \>200 copies/mL in the 48 weeks prior to Step 1 entry.
• One HIV-1 RNA 200-500 copies/mL in the 24 weeks prior to Step 1 entry that is not immediately preceded and followed by HIV-1 RNA \<50 copies/mL.
• NOTE: The preceding viral load \<50 copies/mL may be \>24 weeks prior to Step 1 entry.
• Confirmed systolic blood pressure \>160 mmHg or \<100 mmHg or diastolic blood pressure \>100 mmHg.
• Known untreated renal artery stenosis.
• Known cirrhosis or severe liver disease (eg, ascites, encephalopathy, history of variceal bleeding).
• NOTE: Potential subjects with chronic hepatitis B or C virus infection with no known cirrhosis or severe liver disease may participate in the study, provided there are no plans to start therapy for hepatitis C infection during the 48-week study duration.
• Unstable coronary artery disease/angina or decompensated congestive heart failure.
• Either breastfeeding or pregnant within 24 weeks prior to Step 1 entry.
• Use of thiazolidinediones or any angiotensin receptor blocker (ARB) or angiotensin converting enzyme inhibitor (ACEi) in the 24 weeks prior to Step 1 entry. If the subject took either of these classes of medications for less than 2 weeks in the 24 weeks prior to Step 1 entry, the subject may enroll if 30 days have passed since the last dose. If the subject is diabetic and/or has a calculated glomerular filtration rate (GFR) \<60mL/min, aliskiren-containing medications are also prohibited.
• History of intolerance, other than cough, to any ARB or ACEi.
• Use of anticoagulants other than aspirin 81 mg or 325 mg daily. NOTE: If the subject is on aspirin 81 mg or 325 mg daily and is willing/able to stop therapy for 7 days prior to the biopsy procedures, the subject may enroll.
• Any known bleeding disorder or coagulopathy.
• Projected need for daily potassium supplementation for ≥2 weeks during the study period.
• The following laboratory values obtained within 30 days prior to Step 1 entry by any US laboratory that has a CLIA certification or its equivalent:

Sponsors & Collaborators

• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (12)

UCLA CARE Center CRS (601)

Los Angeles, California, 90035, United States

Location

University of Colorado Hospital CRS (6101)

Aurora, Colorado, 80045, United States

Location

Massachusetts General Hospital ACTG CRS (101)

Boston, Massachusetts, 02114, United States

Location

Washington U CRS (2101)

St Louis, Missouri, 63110, United States

Location

University of Rochester Adult HIV Therapeutic Strategies Network CRS (31787)

Rochester, New York, 14642, United States

Location

Unc Aids Crs (3201)

Chapel Hill, North Carolina, 27514, United States

Location

Univ. of Cincinnati CRS (2401)

Cincinnati, Ohio, 45267, United States

Location

Case CRS (2501)

Cleveland, Ohio, 44106, United States

Location

Vanderbilt Therapeutics CRS (3652)

Nashville, Tennessee, 37232, United States

Location

Houston AIDS Research Team CRS (31473)

Houston, Texas, 77030, United States

Location

University of Washington AIDS CRS (1401)

Seattle, Washington, 98104, United States

Location

Puerto Rico-AIDS CRS (5401)

San Juan, 00935, Puerto Rico

Location

Related Links

• The DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004 (Clarification, August 2009)

MeSH Terms

Interventions

Telmisartan

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: ACTG Clinicaltrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.

ACTGCT.Gov@s-3.com

(301) 628-3313

Study Officials

• Jordan E. Lake, MD, MSc

  The University of Texas Health Science Center, Houston

  STUDY CHAIR

• Netanya Sandler, MD

  The University of Texas Medical Branch, Galveston

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2013
• First Posted: August 27, 2013
• Study Start: January 1, 2014
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: August 3, 2021
• Results First Posted: April 12, 2017

Record last verified: 2020-06

Locations

PR (1); US (11)