Studies of insulin action in patients at increased vascular risk: modulation by anti-hypertensive and endocrine replacement therapy
| ISRCTN | ISRCTN84921696 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN84921696 |
| Secondary identifying numbers | RGHT000278 |
- Submission date
- 12/09/2006
- Registration date
- 25/01/2008
- Last edited
- 17/02/2015
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nutritional, Metabolic, Endocrine
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Prof Patrick Bell
Scientific
Scientific
East Wing
Royal Victoria Hospital
Grosvenor Road
Belfast
BT12 6BA
United Kingdom
| Phone | +44 (0)289 063 3423 |
|---|---|
| patrick.bell@royalhospitals.n-i.nhs.uk |
Study information
| Study design | Randomised double-blind placebo-controlled cross-over study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Studies of insulin action in patients at increased vascular risk: modulation by anti-hypertensive and endocrine replacement therapy |
| Study objectives | Insulin resistance is present in common clinical conditions including diabetes and hypertension, and in less common ones such as hypopituitarism. Each of these is associated with vascular risk and increasing evidence suggests that insulin resistance may contribute. The studies described aim to define better how treatment interventions in these conditions affect insulin sensitivity. Studies in the Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital, Belfast, using detailed assessment of insulin action in carefully controlled protocols have influenced the debate about the most appropriate anti-hypertensive treatment. Our most recent data suggest that combining thiazide diuretics even at low doses with an angiotensin converting enzyme (ACE) inhibitor will increase insulin resistance in hypertensive type two diabetic patients. We plan a similar comparison in nondiabetic hypertensive patients in whom this efficacious combination may be without this adverse effect. We will also compare low dose thiazide/ACE inhibitor with calcium channel blocker/ACE inhibitor, a key choice in current guidelines. We have previously investigated the impact of hydrocortisone and growth hormone on insulin action in hypopituitarism. Levels of dehydroepiandrosterone (DHEA), an adrenal steroid hormone, are reduced in hypopituitarism. DHEA is available in the United States of America (USA) as replacement therapy and has been shown to improve quality of life in patients with hypoadrenalism. Its effect on insulin sensitivity is controversial and has not been widely researched in patients with hypopituitarism. Using a placebo controlled cross-over trial, we plan to study DHEA replacement in hypopituitarism. The results of the studies described will influence future therapeutic approaches in these at risk patients. |
| Ethics approval(s) | Office for Research Ethics Committee in Northern Ireland (ORECNI), 29/08/2006, ref: 06/NIR03/93 |
| Health condition(s) or problem(s) studied | Hypertension, type 2 diabetes, hypopituitarism |
| Intervention | Protocols one and two: Medications will be withdrawn and replaced with placebo for a six week run in. Patients will be randomised to captopril plus study drug (bendroflumethiazide) or captopril plus placebo in protocol one and captopril plus bendroflumethiazide or plus amlodipine in protocol two for 12 weeks. There will be a six week washout, then cross over to the alternative study arm. Protocol three: Hydrocortisone therapy will be standardised for four weeks. Patients will receive either dehydroepiandrosterone or placebo for 12 weeks. As for previous protocols, there will be a six week wash out then cross over to the other treatment arm. Insulin action will be assessed after placebo run in and each 12 weeks study period using the hyperinsulinaemic euglycaemic clamp method. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Captopril, bendroflumethiazide, amlodipine |
| Primary outcome measure | Insulin resistance |
| Secondary outcome measures | Quality of life following dehydroepiandrosterone replacement |
| Overall study start date | 19/09/2006 |
| Completion date | 01/08/2008 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 45 |
| Key inclusion criteria | 1. Under 65 years old 2. Protocol one: essential hypertension, mild or newly diagnosed 3. Protocol two: type two diabetes and hypertension 4. Protocol 3: hypopituitarism, female, low basal DHEA levels |
| Key exclusion criteria | 1. Secondary hypertension 2. Obesity 3. Cardiac, renal or hepatic disease 4. History of gout 5. Those in receipt of any additional medications that may affect insulin action 6. Type two diabetics with dipstick positive proteinuria |
| Date of first enrolment | 19/09/2006 |
| Date of final enrolment | 01/08/2008 |
Locations
Countries of recruitment
- Northern Ireland
- United Kingdom
Study participating centre
Royal Victoria Hospital
Belfast
BT12 6BA
United Kingdom
BT12 6BA
United Kingdom
Sponsor information
Royal Group Hospitals Trust (UK)
Hospital/treatment centre
Hospital/treatment centre
Grosvenor Road
Belfast
BT12 6BA
Northern Ireland
United Kingdom
| Phone | +44 (0)289 063 2224 |
|---|---|
| mary.williams@royalhospitals.n-i.nhs.uk | |
"ROR" |
https://ror.org/03rq50d77 |
Funders
Funder type
Government
Research and Development Office (UK) - Department of Health and Social Security
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| 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? |
|---|---|---|---|---|---|
| Results article | results | 01/09/2012 | Yes | No | |
| Results article | results | 01/04/2013 | Yes | No |
