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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; 5(10):e009566BO

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.

Authors+Show Affiliations

Department of Molecular and Clinical Pharmacology, The Wolfson Centre for Personalised Medicine, University of Liverpool, Liverpool, UK MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, UK Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.Clinical Trials Research Centre, University of Liverpool, Liverpool, UK.Clinical Trials Research Centre, University of Liverpool, Liverpool, UK Department of Biostatistics, University of Liverpool, Liverpool, UK.Clinical Trials Research Centre, University of Liverpool, Liverpool, UK.Department of Diabetes and Endocrinology, The Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK.Department of Biostatistics, University of Liverpool, Liverpool, UK.Magnetic Resonance and Image Analysis Research Centre, University of Liverpool, Liverpool, UK.Department of Mathematics and Statistics, Lancaster University, Lancaster, UK.Department of Mathematics and Statistics, Lancaster University, Lancaster, UK.Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.Clinical Trials Research Centre, University of Liverpool, Liverpool, UK Department of Biostatistics, University of Liverpool, Liverpool, UK.Department of Molecular and Clinical Pharmacology, The Wolfson Centre for Personalised Medicine, University of Liverpool, Liverpool, UK MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, UK Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.

Pub Type(s)

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

Language

eng

PubMed ID

26474943

Citation

Pushpakom, Sudeep P., et al. "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, vol. 5, no. 10, 2015, pp. e009566.
Pushpakom SP, Taylor C, Kolamunnage-Dona R, et al. 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;5(10):e009566.
Pushpakom, S. P., Taylor, C., Kolamunnage-Dona, R., Spowart, C., Vora, J., García-Fiñana, M., ... Pirmohamed, M. (2015). 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, 5(10), pp. e009566. doi:10.1136/bmjopen-2015-009566.
Pushpakom SP, et al. 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. PubMed PMID: 26474943.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Pushpakom,Sudeep P, AU - Taylor,Claire, AU - Kolamunnage-Dona,Ruwanthi, AU - Spowart,Catherine, AU - Vora,Jiten, AU - García-Fiñana,Marta, AU - Kemp,Graham J, AU - Whitehead,John, AU - Jaki,Thomas, AU - Khoo,Saye, AU - Williamson,Paula, AU - Pirmohamed,Munir, Y1 - 2015/10/15/ PY - 2015/10/18/entrez PY - 2015/10/18/pubmed PY - 2016/8/2/medline SP - e009566 EP - e009566 JF - BMJ open JO - BMJ Open VL - 5 IS - 10 N2 - 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. SN - 2044-6055 UR - https://www.unboundmedicine.com/medline/citation/26474943/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_ L2 - http://bmjopen.bmj.com/cgi/pmidlookup?view=long&pmid=26474943 DB - PRIME DP - Unbound Medicine ER -