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
4. 80mg telmisartan
Intervention type
Other
Phase
Phase II
Drug names
Primary outcome measure
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
08/06/2017
Reason abandoned (if study stopped)
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
19/03/2013
Recruitment end date
20/07/2015
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Molecular and Clinical Pharmacology
Liverpool
L69 3GL
United Kingdom
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
31/12/2017
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2015 protocol in http://www.ncbi.nlm.nih.gov/pubmed/26474943