Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
RGHT 000298
Study information
Scientific title
Insulin action and hypertension: effects of hyperaldosteronism and its treatment
Acronym
Study hypothesis
Many common conditions such as type two diabetes and hypertension, as well as less common conditions such as hypopituitarism and secondary hypertension are associated with insulin resistance. All are associated with increased vascular risk to which insulin resistance may contribute. The study seeks to determine how to characterise and treat hypertensive patients with special reference to the influence of insulin action.
The link between increased insulin resistance, diabetes and essential hypertension has prompted concern regarding deleterious effects of antihypertensive therapy on glucose and lipid metabolism. Evidence that commonly prescribed agents may increase insulin resistance and that this may lessen the beneficial impact of tight blood pressure control on cardiovascular endpoints has led to much debate regarding appropriate choice of drug treatment. The continued use of older agents, in particular thiazide diuretics, has been supported by one recent large trial but shown to be associated with a less favourable outcome in another.
Recent trials have also demonstrated a protective effect of aldosterone antagonist therapy in heart failure and left ventricular dysfunction after myocardial infarction. Despite these advances little is known of the effect on insulin resistance of aldosterone antagonist drugs such as spironolactone or the new agent, eplerenone.
The first study outlined seeks to determine the effect of eplerenone on insulin action in essential hypertension using a double blind, cross-over protocol.
Ethics approval
The Office for Research Ethics Committee in Northern Ireland (ORECNI), 13/05/2008, ref: 08/NIR01/12
Study design
Randomised controlled crossover double-blind trial
Primary study design
Interventional
Secondary study design
Randomised cross over 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 and insulin resistance
Intervention
A randomised double-blind control crossover design will be employed. All antihypertensive agents will be withdrawn and placebo substituted for six weeks. During this period blood pressure will be monitored every two weeks. There will be two study periods of 12 weeks during which blood pressure will be measured after two weeks and then every four weeks, separated by a six-week washout during which blood pressure will be measured every two weeks. It is no longer ethical to compare with placebo and so we will compare with doxazosin, which has been shown to be neutral in its effect on insulin action. Patients will be started on eplerenone 25 mg twice daily or doxazosin 1 mg twice daily for the first week, 2 mg twice daily thereafter.
Insulin action will be assessed at the end of the placebo run in and after each of the two study periods. Twenty-four hour ambulatory blood pressure monitoring will be performed in the last week of placebo run-in and each treatment period. If, during the study (including during placebo run-in or wash-out), systolic blood pressure rises above 160 mmHg or diastolic blood pressure rises above 100 mmHg on any occasion, or above 160 and 95 mmHg on two occasions, additional therapy with doxazosin will be given, with the addition of up to 12 mg of doxazosin. Serum creatinine and potassium will be measured at baseline and every four weeks during the active treatment periods.
Intervention type
Drug
Phase
Not Applicable
Drug names
Insulin (eplerenone), doxazosin
Primary outcome measure
Insulin action will be measured by performing a hyperinsulinaemic, euglycaemic clamp, measured at the end of weeks 6, 18 and 36.
Secondary outcome measures
Blood pressure will be measured using a standard automated blood pressure machine, measured at the end of weeks 2, 4, 6, 8, 12, 16, 18, 20, 22, 24, 26, 30, 34 and 36.
Overall trial start date
15/08/2008
Overall trial end date
15/08/2010
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Patients aged under 70 years, either sex
2. Mild essential hypertension
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
16
Participant exclusion criteria
1. Presence of diabetes mellitus
2. Significant obesity (body mass index [BMI] exceeding 35 kg/m^2)
3. Cardiac, renal or hepatic disease
4. A history of gout
5. Any treatment that may affect insulin action
6. Hyperkalaemia
7. Taking potassium sparing diuretics, potassium supplements or strong inhibitors of CYP 34A
8. Women who are pregnant or breastfeeding
9. Secondary hypertension
10. Diastolic blood pressure outside 80 - 105 mmHg range after placebo run-in of six weeks
11. Not capable of giving informed consent
Recruitment start date
15/08/2008
Recruitment end date
15/08/2010
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Royal Victoria Hospital
Belfast
BT12 6BA
United Kingdom
Sponsor information
Organisation
Belfast Health and Social Care Trust (UK)
Sponsor details
Royal Research Office
First Floor
Education Centre
Royal Victoria Hospital
Grosvenor Road
Belfast
BT12 6BA
United Kingdom
Sponsor type
Government
Website
Funders
Funder type
Government
Funder name
Northern Ireland Research and Development Office (UK) - Recognised Research Group Funding (ref: RRG 5.46)
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
Basic results (scientific)
Publication list
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/24739799