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)
| ISRCTN | ISRCTN51069819 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN51069819 |
| EudraCT/CTIS number | 2012-000935-18 |
| Secondary identifying numbers | 12578 |
- Submission date
- 29/06/2012
- Registration date
- 29/06/2012
- Last edited
- 21/08/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Dr Sudeep Pushpakom
Scientific
Scientific
Molecular and Clinical Pharmacology
1-3 Brownlow Street
Liverpool
L69 3GL
United Kingdom
| Phone | +44 151 795 5404 |
|---|---|
| sudeepp@liverpool.ac.uk |
Study information
| Study design | Randomised; Interventional; Design type: Not specified, Treatment |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| 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) |
| Study acronym | TAILoR |
| Study objectives | 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(s) | 12/NW/0214; First MREC approval date 02/04/2012 |
| Health condition(s) or problem(s) studied | 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 |
| 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 study start date | 01/08/2012 |
| Completion date | 08/06/2017 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 370; UK Sample Size: 370 |
| Total final enrolment | 377 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 19/03/2013 |
| Date of final enrolment | 20/07/2015 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Molecular and Clinical Pharmacology
Liverpool
L69 3GL
United Kingdom
L69 3GL
United Kingdom
Sponsor information
University of Liverpool (UK)
University/education
University/education
Wolfson Centre for Personalised Medicine
Department of Pharmacology
Block A: Waterhouse Buildings 1-5 Brownlow Street
Liverpool
L69 3GL
England
United Kingdom
"ROR" |
https://ror.org/04xs57h96 |
|---|
Funders
Funder type
Government
NIHR Efficacy and Mechanism Evaluation (UK)
No information available
Results and Publications
| Intention to publish date | 31/12/2017 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 15/10/2015 | Yes | No | |
| Results article | results | 06/05/2020 | 21/08/2019 | Yes | No |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
21/08/2019: The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.
30/08/2017: Overall trial end date changed from 30/09/2014 to 08/06/2017, recruitment start date from 01/08/2012 to 19/03/2013, recruitment end date from 30/09/2014 to 20/07/2015. Intended publictaion date
19/10/2015: Publication reference added.
