| Source of record | UK Trials |
| ISRCTN | ISRCTN84921696 |
| Date ISRCTN assigned | 25/01/2008 |
| Local reference number(s) | RGHT000278 |
| Public title | Studies of insulin action in patients at increased vascular risk: modulation by anti-hypertensive and endocrine replacement therapy |
| Scientific title |
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| Acronym | N/A |
| Disease/condition/study domain | Hypertension, type two diabetes, hypopituitarism |
| Study hypothesis | 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. |
| Design/methodology | Randomised double blind placebo controlled cross-over study |
| Research ethics review | Ethical approval received from the Office for Research Ethics Committee in Northern Ireland (ORECNI) on the 29th August 2006 (ref: 06/NIR03/93). |
| Countries of trial | United Kingdom |
| Participants - 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 |
| Participants - 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 |
| Patient information material | Not available in web format, please use the contact details below to request a patient information sheet |
| Anticipated start date | 19/09/2006 |
| Anticipated end date | 01/08/2008 |
| Status of trial | Ongoing |
| Target number of participants | 45 |
| Interventions | 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. |
| Primary outcome measure(s) | Insulin resistance. |
| Secondary outcome measure(s) | Quality of life following dehydroepiandrosterone replacement. |
| Sources of funding | Research and Development Office (UK) - Department of Health and Social Security |
| Sponsor name | Royal Group Hospitals Trust (UK) |
| Sponsor details | Grosvenor Road
Belfast
United Kingdom
BT12 6BA |
| Sponsor telephone | +44 (0)28 9063 2224 |
| Sponsor fax | +44 (0)28 9063 4812 |
| Sponsor email | mary.williams@royalhospitals.n-i.nhs.uk |
| Contact name | Prof Patrick Bell |
| Contact details | East Wing
Royal Victoria Hospital
Grosvenor Road
Belfast
United Kingdom
BT12 6BA |
| Contact telephone | +44 (0)28 9063 3423 |
| Contact fax | +44 (0)28 9031 0111 |
| Contact email | patrick.bell@royalhospitals.n-i.nhs.uk |
| More information | For more up-to-date information please go to the ISRCTN link below. |
| Link to record in ISRCTN Register | ISRCTN84921696 |
| Date last extracted from ISRCTN register | 17/04/2008 |
