Telmisartan and Insulin Resistance in HIV (TAILoR): protocol for a dose-ranging phase II randomised open-labelled trial of telmisartan as a strategy for the reduction of insulin resistance in HIV-positive individuals on combination antiretroviral therapy

BMJ Open. 2015 Oct 15;5(10):e009566. doi: 10.1136/bmjopen-2015-009566.

Abstract

Introduction: Telmisartan, an angiotensin receptor blocker, has beneficial effects on insulin resistance and cardiovascular health in non-HIV populations. This trial will evaluate whether telmisartan can reduce insulin resistance in HIV-positive individuals on combination antiretroviral therapy.

Methods and analysis: This is a phase II, multicentre, randomised, open-labelled, dose-ranging trial of telmisartan in 336 HIV-positive individuals over a period of 48 weeks. The trial will use an adaptive design to inform the optimal dose of telmisartan. Patients will be randomised initially 1:1:1:1 to receive one of the three doses of telmisartan (20, 40 and 80 mg) or no intervention (control). An interim analysis will be performed when half of the planned maximum of 336 patients have been followed up for at least 24 weeks. The second stage of the study will depend on the results of interim analysis. The primary outcome measure is a reduction in insulin resistance (as measured by Homeostatic Model Assessment-Insulin Resistance (HOMA-IR)) in telmisartan treated arm(s) after 24 weeks of treatment in comparison with the non-intervention arm. The secondary outcome measures include changes in lipid profile; body fat redistribution (as measured by MRI); plasma and urinary levels of various biomarkers of cardiometabolic and renal health at 12, 24 and 48 weeks. Serious adverse events will be compared between different telmisartan treated dose arm(s) and the control arm.

Ethics and dissemination: The study, this protocol and related documents have been approved by the National Research Ethics Service Committee North West-Liverpool Central (Ref: 12/NW/0214). On successful completion, study data will be shared with academic collaborators. The findings from TAILoR will be disseminated through peer-reviewed publications, at scientific conferences, the media and through patient and public involvement.

Trial registration numbers: 04196/0024/001-0001;

Eudract: 2012-000935-18;

Isrctn: 51069819.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antihypertensive Agents / administration & dosage*
  • Antihypertensive Agents / adverse effects
  • Antiretroviral Therapy, Highly Active / methods
  • Benzimidazoles / administration & dosage*
  • Benzimidazoles / adverse effects
  • Benzoates / administration & dosage*
  • Benzoates / adverse effects
  • Clinical Protocols
  • Drug Therapy, Combination
  • Female
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • Humans
  • Insulin Resistance*
  • Male
  • Middle Aged
  • Research Design*
  • Telmisartan
  • Young Adult

Substances

  • Antihypertensive Agents
  • Benzimidazoles
  • Benzoates
  • Telmisartan

Associated data

  • EudraCT/2012-000935-18
  • ISRCTN/ISRCTN51069819