Contact information
Type
Scientific
Primary contact
Prof Patrick Bell
ORCID ID
Contact details
East Wing
Royal Victoria Hospital
Grosvenor Road
Belfast
BT12 6BA
United Kingdom
+44 (0)289 063 3423
patrick.bell@royalhospitals.n-i.nhs.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
RGHT000278
Study information
Scientific title
Studies of insulin action in patients at increased vascular risk: modulation by anti-hypertensive and endocrine replacement therapy
Acronym
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.
Ethics approval
Office for Research Ethics Committee in Northern Ireland (ORECNI), 29/08/2006, ref: 06/NIR03/93
Study design
Randomised double-blind placebo-controlled cross-over study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
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
Phase
Not Applicable
Drug names
Captopril, bendroflumethiazide, amlodipine
Primary outcome measures
Insulin resistance
Secondary outcome measures
Quality of life following dehydroepiandrosterone replacement
Overall trial start date
19/09/2006
Overall trial end date
01/08/2008
Reason abandoned
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
45
Participant 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
Recruitment start date
19/09/2006
Recruitment end date
01/08/2008
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Royal Victoria Hospital
Belfast
BT12 6BA
United Kingdom
Sponsor information
Organisation
Royal Group Hospitals Trust (UK)
Sponsor details
Grosvenor Road
Belfast
BT12 6BA
United Kingdom
+44 (0)289 063 2224
mary.williams@royalhospitals.n-i.nhs.uk
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Government
Funder name
Research and Development Office (UK) - Department of Health and Social Security
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
2012 results in: http://www.ncbi.nlm.nih.gov/pubmed/22420492
2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/23424237