Insulin action and hypertension: effects of hyperaldosteronism and its treatment
| ISRCTN | ISRCTN21269614 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN21269614 |
| Secondary identifying numbers | RGHT 000298 |
- Submission date
- 30/07/2008
- Registration date
- 23/09/2008
- Last edited
- 06/06/2016
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Circulatory System
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Prof Patrick Bell
Scientific
Scientific
East Wing
Royal Victoria Hospital
Grosvenor Road
Belfast
BT12 6BA
United Kingdom
Study information
| Study design | Randomised controlled crossover double-blind trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised cross over trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Insulin action and hypertension: effects of hyperaldosteronism and its treatment |
| Study objectives | 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(s) | The Office for Research Ethics Committee in Northern Ireland (ORECNI), 13/05/2008, ref: 08/NIR01/12 |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | 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 study start date | 15/08/2008 |
| Completion date | 15/08/2010 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 16 |
| Key inclusion criteria | 1. Patients aged under 70 years, either sex 2. Mild essential hypertension |
| Key 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 |
| Date of first enrolment | 15/08/2008 |
| Date of final enrolment | 15/08/2010 |
Locations
Countries of recruitment
- Northern Ireland
- United Kingdom
Study participating centre
Royal Victoria Hospital
Belfast
BT12 6BA
United Kingdom
BT12 6BA
United Kingdom
Sponsor information
Belfast Health and Social Care Trust (UK)
Hospital/treatment centre
Hospital/treatment centre
Royal Research Office
First Floor, Education Centre
Royal Victoria Hospital
Grosvenor Road
Belfast
BT12 6BA
Northern Ireland
United Kingdom
| Website | http://www.belfasttrust.hscni.net/ |
|---|---|
"ROR" |
https://ror.org/02tdmfk69 |
Funders
Funder type
Government
Northern Ireland Research and Development Office (UK) - Recognised Research Group Funding (ref: RRG 5.46)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/10/2014 | Yes | No |
Editorial Notes
06/06/2016: Publication reference added.
