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

This study is not yet open for participant recruitment.
Verified August 2013 by AIDS Clinical Trials Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT01928927
First received: August 22, 2013
Last updated: NA
Last verified: August 2013
History: No changes posted
  Purpose

The main goal of this study is to see if a drug called telmisartan will decrease fibrosis (scarring) and inflammation (irritation) in people who are infected with HIV and doing well on their HIV medications. The study is also being 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.


Condition Intervention Phase
HIV-1 Infection
Drug: Telmisartan
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effects of Telmisartan on Fibrotic and Inflammatory Contributors to End-Organ Disease in HIV-Infected Patients Well Controlled on Antiretroviral Therapy

Resource links provided by NLM:


Further study details as provided by AIDS Clinical Trials Group:

Primary Outcome Measures:
  • Change in percent collagen deposition on lymph node pathology from baseline to week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Percent collagen deposition defined as proportion of fibrotic/collagen area to total area

  • Change in percent collagen deposition on subcutaneous abdominal adipose tissue pathology from baseline to week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Percent collagen deposition defined as proportion of fibrotic/collagen area to total area


Secondary Outcome Measures:
  • Change in biomarkers associated with inflammation, coagulation, and oxidative stress from baseline to week 4 [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Measured as change from entry to week 4 in circulating hyaluronic acid, IL-6, TNF-alpha, sCD14, D-dimer, tissue factor, soluble TNF-alpha receptor levels.

  • Change in biomarkers associated with inflammation, coagulation, and oxidative stress from baseline to week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Measured as change from entry to week 24 in circulating hyaluronic acid, IL-6, TNF-alpha, sCD14, D-dimer, tissue factor, soluble TNF-alpha receptor levels.

  • Change in biomarkers associated with inflammation, coagulation, and oxidative stress from baseline to week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Measured as change from entry to week 48 in circulating hyaluronic acid, IL-6, TNF-alpha, sCD14, D-dimer, tissue factor, soluble TNF-alpha receptor levels.

  • Change in circulating activated T cells from baseline to week 4 [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Measured as change from entry to week 4 in the percentage of CD4 and CD8 cells that are CD38+/HLA-DR+

  • Change in circulating activated T cells from baseline to week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Measured as change from entry to week 24 in the percentage of CD4 and CD8 cells that are CD38+/HLA-DR+

  • Change in circulating activated T cells from baseline to week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Measured as change from entry to week 48 in the percentage of CD4 and CD8 cells that are CD38+/HLA-DR+

  • Change in inflammatory cell population type and number in lymphoid tissue biopsy specimens from baseline to week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Measured as the change from entry to week 48 in the frequency of CD14+, CD16+,CD64+, and/or CD163+ macrophages and % activated (CD38+/HLA-DR+, Ki67+) CD4 and CD8 T cells.

  • Change in inflammatory cell population type and number in adipose tissue biopsy specimens from baseline to week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Measured as the change from entry to week 48 in the frequency of CD14+, CD16+,CD64+, and/or CD163+ macrophages.

  • Change in the proportion of CD4+ T cells in lymphoid tissue from baseline to week 48. [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Measured as the change from entry to week 48 in %CD3+CD4+ T cells.

  • Change in circulating CD4+ T cell count and phenotype of circulating CD4+ T cells from baseline to weeks 24. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Measured as the change from entry to week 24 in CD4+ T cell count and memory/naïve phenotype of the CD4+ T cells.

  • Change in circulating CD4+ T cell count and phenotype of circulating CD4+ T cells from baseline to weeks 48. [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Measured as the change from entry to week 48 in CD4+ T cell count and memory/naïve phenotype of the CD4+ T cells.

  • Change in markers of peripheral insulin resistance and dyslipidemia from baseline to week 48. [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Measured as change from entry to week 48 in HOMA-IR, fasting total cholesterol, fasting HDL cholesterol, fasting calculated LDL cholesterol, and fasting triglycerides.

  • Change in anthropometric measurements from baseline to week 24. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Measures as change from study entry to week 24 in mid-waist circumference and waist-to-hip ratio

  • Change in anthropometric measurements from baseline to week 48. [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Measures as change from study entry to week 48 in mid-waist circumference and waist-to-hip ratio

  • Prevalence of metabolic syndrome at week 24. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

    Components of the metabolic syndrome will be defined according to the 2004 updated National Cholesterol Education Program Adult Treatment Panel III [NCEP ATP III] criteria) as the presence of any 3 of the following: Waist: >40" (101.6 cm) in men, >35" (88.9 cm) in women with the exception of Asian-Americans: >35" (88.9 cm) in men, 31" (78.7 cm) in women; Fasting HDL-C <40 mg/dL in men, <50 mg/dL in women; Fasting TG ≥150 mg/dL; Diastolic blood pressure ≥85 mmHg or systolic blood pressure ≥130 mmHg; Fasting plasma glucose ≥100 mg/dL.

    NOTE: This definition of metabolic syndrome may be subject to change in accordance with current guidelines at the time of the final analysis. It will be defined in the Final Statistical Analysis Plan prior to data review for final analysis.


  • Prevalence of metabolic syndrome at week 48. [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

    Components of the metabolic syndrome will be defined according to the 2004 updated National Cholesterol Education Program Adult Treatment Panel III [NCEP ATP III] criteria) as the presence of any 3 of the following: Waist: >40" (101.6 cm) in men, >35" (88.9 cm) in women with the exception of Asian-Americans: >35" (88.9 cm) in men, 31" (78.7 cm) in women; Fasting HDL-C <40 mg/dL in men, <50 mg/dL in women; Fasting TG ≥150 mg/dL; Diastolic blood pressure ≥85 mmHg or systolic blood pressure ≥130 mmHg; Fasting plasma glucose ≥100 mg/dL.

    NOTE: This definition of metabolic syndrome may be subject to change in accordance with current guidelines at the time of the final analysis. It will be defined in the Final Statistical Analysis Plan prior to data review for final analysis.


  • Safety profile of telmisartan over the 48-week study period. [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]

    Presence of any of the following: Grade >/=2 signs and symptoms, any sign or symptom (of any Grade) that lead to study treatment discontinuation, and the site-determined relatedness of AEs/signs/symptoms to telmisartan therapy.

    NOTE: As adipose tissue and lymph node biopsies are generally considered to be minimal risk procedures, biopsy safety profile will not formally be evaluated as an endpoint in this protocol.



Estimated Enrollment: 54
Study Start Date: August 2013
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: Telmisartan
Participants will receive Telmisartan 40 mg daily during weeks 0-4 followed by telmisartan 80 mg daily during weeks 5-48.
Drug: Telmisartan
No Intervention: Arm B: No study drug, week 0-48 evaluations

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Step 1 Inclusion Criteria:

  • 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/m2.
  • 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.

Step 2 Inclusion Criteria:

  • Entry lymphoid tissue and adipose tissue specimen for assay of the primary endpoint has been obtained.
  • Willingness to undergo the week 48 lymphoid and adipose tissue biopsies.

Step 1 Exclusion Criteria:

  • 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:

    • Absolute neutrophil count (ANC) ≤750 cells/mm3
    • Hemoglobin ≤10 g/dL
    • Platelet count ≤75,000/mm3
    • Calculated creatinine clearance (CrCl) <50 mL/min, as estimated by the Cockcroft-Gault equation
    • Aspartate aminotransferase (AST) (SGOT) >/=3x ULN (upper limit of normal)
    • Alanine aminotransferase (ALT) (SGPT) >/=3x ULN
    • Partial thromboplastin time (PTT) >1.2x ULN
    • Prothrombin time (PT) >1.2x ULN
  • Heritable connective tissue disorders (eg Ehlers-Danlos syndrome, osteogenesis imperfecta, Stickler syndrome, Marfan's syndrome).

NOTE: Subjects with acquired/autoimmune chronic inflammatory diseases/connective tissue disorders who are clinically stable (in the opinion of the site investigator) and not on a prohibited medication may enroll with approval of the A5317 study chairs.

  • Serious illness requiring systemic treatment and/or hospitalization until subject either completes therapy or is clinically stable on therapy, in the opinion of the site investigator, for at least 7 days prior to Step 1 entry.
  • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
  • Any condition that, in the opinion of the site investigator, would compromise the subject's ability to participate in the study.

Step 2 Exclusion Criteria:

  • Any AE associated with the Step 1 entry biopsy that would exclude the subject from undergoing follow-up biopsy at week 48.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01928927

Sponsors and Collaborators
AIDS Clinical Trials Group
Investigators
Study Chair: Jordan E. Lake, MD, MSc UCLA Care Center
Study Chair: Netanya Sandler, MD University of Texas Medical Branch at Galveston
  More Information

No publications provided

Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT01928927     History of Changes
Other Study ID Numbers: ACTG A5317, UM1AI068636
Study First Received: August 22, 2013
Last Updated: August 22, 2013
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Telmisartan
Benzoates
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 15, 2014