Condition category
Circulatory System
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information



Primary contact

Prof Patrick Bell


Contact details

East Wing
Royal Victoria Hospital
Grosvenor Road
BT12 6BA
United Kingdom

Additional identifiers

EudraCT number number

Protocol/serial number

RGHT 000298

Study information

Scientific title

Insulin action and hypertension: effects of hyperaldosteronism and its treatment


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


Secondary study design

Randomised cross over trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet


Hypertension and insulin resistance


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



Not Applicable

Drug names

Insulin (eplerenone), doxazosin

Primary outcome measures

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


Overall trial end date


Reason abandoned


Participant inclusion criteria

1. Patients aged under 70 years, either sex
2. Mild essential hypertension

Participant type


Age group




Target number of participants


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


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

Royal Victoria Hospital
BT12 6BA
United Kingdom

Sponsor information


Belfast Health and Social Care Trust (UK)

Sponsor details

Royal Research Office
First Floor
Education Centre
Royal Victoria Hospital
Grosvenor Road
BT12 6BA
United Kingdom

Sponsor type




Funder type


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


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

2014 results in:

Publication citations

Additional files

Editorial Notes

06/06/2016: Publication reference added.