Condition category
Infections and Infestations
Date applied
29/06/2012
Date assigned
29/06/2012
Last edited
19/10/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Sudeep Pushpakom

ORCID ID

Contact details

Molecular and Clinical Pharmacology
1-3 Brownlow Street
Liverpool
L69 3GL
United Kingdom
+44 151 795 5404
sudeepp@liverpool.ac.uk

Additional identifiers

EudraCT number

2012-000935-18

ClinicalTrials.gov number

Protocol/serial number

12578

Study information

Scientific title

TAILoR - (TelmisArtan and InsuLin Resistance in HIV): 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 (cART)

Acronym

TAILoR

Study hypothesis

TAILoR is a phase II multi-centre, randomised, open labelled, dose ranging trial of telmisartan in HIV-positive individuals on combination antiretroviral therapy (cART) to investigate whether telmisartan can reduce insulin resistance observed in this patient population.

Patients with HIV treated by cART are at risk of developing certain serious side effects such as reduced response to insulin (insulin resistance), abnormal body fat distribution (HIV lipodystrophy) and high cholesterol levels leading to diabetes, and importantly, an increase in the risk of cardiovascular disease. A key abnormality seems to be insulin resistance which will develop in almost all patients during the course of anti-HIV therapy. There is a need to find new strategies to reduce insulin resistance in HIV-positive individuals treated with cART, which ultimately will reduce the associated cardiovascular risk.

Telmisartan, a widely used anti hypertensive drug, has been shown to reduce insulin resistance and improve various indicators (biomarkers) of cardiovascular health in non-HIV population. However, whether telmisartan is effective for insulin resistance and other metabolic side effects in HIV patients treated by cART is not known. We also need to identify the most appropriate dose of telmisartan that is effective in reducing the metabolic side effects in HIV patients.

TAILoR will use a novel adaptive trial design to compare three different doses of telmisartan with the control group (those who do not take telmisartan) to determine the effect on insulin resistance over a period of 48 weeks. We will recruit 370 HIV-positive patients from multiple specialist centres across the UK and patients will be randomised to one of the four arms. If telmisartan shows a significant beneficial effect on insulin resistance, a larger phase III study to assess its effect on cardiovascular morbidity will be conducted in HIV-positive individuals treated with cART.

Ethics approval

12/NW/0214; First MREC approval date 02/04/2012

Study design

Randomised; Interventional; Design type: Not specified, Treatment

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Topic: Infection; Subtopic: Infection (all Subtopics); Disease: Infectious diseases and microbiology

Intervention

There are four groups in the study:
1. A control non-intervention group
2. 20mg telmisartan (intervention)
3. 40mg telmisartan and
4. 80mg telmisartan

Intervention type

Other

Phase

Phase II

Drug names

Primary outcome measures

Reduction in insulin resistance [as measured by homeostasis model assessment-estimated insulin resistance (HOMA-IR)] at 24 weeks

Secondary outcome measures

1. Change in body fat distribution at 24 weeks
2. Change in insulin resistance at 48 weeks
3. Change in lipid profile at 12, 24 and 48 weeks
4. Change in plasma concentrations of biomarkers at 12, 24 and 48 weeks
5. Difference in expected and unexpected adverse drug reactions (ADRs) between treatment arms and control arm at 24, 48 weeks

Overall trial start date

01/08/2012

Overall trial end date

30/09/2014

Reason abandoned

Eligibility

Participant inclusion criteria

1. Adult, male and female (age 18 or above) HIV-positive individuals receiving antiretroviral therapy containing a boosted protease inhibitor (lopinavir/ritonavir, atazanavir/ritonavir, darunavir/ritonavir, fosamprenavir/ritonavir, saquinavir/ritonavir) and/or efavirenz, for at least 6 months. The backbone can be based on N(t)RTI, raltegravir or maraviroc.
Patients on protease inhibitor monotherapy will be included if they meet other criteria.
2. Ability to give informed consent
3. Willingness to comply with all study requirements

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 370; UK Sample Size: 370

Participant exclusion criteria

1. Pre-existing diagnosis of type 1 or 2 diabetes (Fasting glucose > 7.2mmol/L or HbA1c = 6.5% [48 mmol/ml] or abnormal OGTT or random plasma glucose = 11mmol/l)
2. Patients known to have consistently low blood pressure (pre-existing hypotension; below a threshold of 100/60 mm Hg)
3. Patients with renal disease Estimated Glomerular Filtration Rate(eGFR) <60 in the 6 months preceding randomisation)
4. Patients with known untreated renal artery stenosis
5. Patients with prior diagnosis of Hepatitis C [a positive polymerase chain reaction (PCR) result in the 6 months preceding randomisation]
6. Patients who are on unboosted atazanavir
7. Patients who are on/ have been on hormone therapy (eg. growth hormone), anabolics (eg. testosterone) and insulin sensitisers (eg. Metformin) within 6 months preceding randomisation. Patients who are on hormonal contraception are eligible
8. Patients who are already on/ have been on other angiotensin receptor blockers (ARBs) and/or angiotensin-converting-enzyme inhibitor (ACE) inhibitors within 4 weeks preceding randomisation
9. Those with suspected poor compliance
10. Pregnant or lactating women
11. Women of childbearing age unless using non hormonal contraception
12. Co-enrolment in other drug trials
13. Patients who have participated in a trial of an investigative medicinal product (IMP) likely to influence insulin sensitivity, plasma insulin, glucose levels or plasma lipid levels within 6 months preceding randomisation
14. For the sub-cohort of patients undergoing MRI/MRS, normal MR exclusion criteria will apply

Recruitment start date

01/08/2012

Recruitment end date

30/09/2014

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Molecular and Clinical Pharmacology
Liverpool
L69 3GL
United Kingdom

Sponsor information

Organisation

University of Liverpool (UK)

Sponsor details

Wolfson Centre for Personalised Medicine
Department of Pharmacology
Block A: Waterhouse Buildings 1-5 Brownlow Street
Liverpool
L69 3GL
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

NIHR Efficacy and Mechanism Evaluation (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2015 protocol in http://www.ncbi.nlm.nih.gov/pubmed/26474943

Publication citations

Additional files

Editorial Notes

19/10/2015: Publication reference added.