Condition category
Nutritional, Metabolic, Endocrine
Date applied
12/09/2006
Date assigned
25/01/2008
Last edited
17/02/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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

Publication citations

Additional files

Editorial Notes