| Source of record | UK Clinical Trials Gateway |
| ISRCTN | ISRCTN76558770 |
| Date ISRCTN assigned | 27/07/2007 |
| Local reference number(s) | SAM 001 |
| Public title | The effects of spironolactone on endothelial function, autonomic function and glycaemic control in diabetic patients with poor blood pressure control |
| Scientific title |
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| Acronym | N/A |
| Disease/condition/study domain | Type 2 diabetes mellitus and hypertension |
| Study hypothesis | Patients with diabetes are at particularly high risk of cardiovascular disease. Infact, macrovascular disease accounts for 70 % of the mortality in type 2 diabetes, making heart attacks and strokes two to four times more frequent in these patients compared to controls. The combination of diabetes and hypertension is a particularly strong cardiovascular risk factor. Vascular endothelial dysfunction is a recognised risk factor for cardiovascular mortality. Blocking aldosterone with spironolactone in patients with cardiac failure can reverse endothelial dysfunction in this patient group, as well as improving the prognostic markers of PIIINP, BNP and heart rate variability. Additionally, the RALES (Randomised Aldactone Evaluation Study) and EPHESUS (Eplerenone Postacute myocardial infarction Heart failure Efficacy and Survival Study) studies have shown a dramatic reduction in total mortality (approximately 30%) with aldosterone blockade in patients with heart failure already taking the recognised optimum treatment for this condition. This lends weight to the concept that reducing endothelial dysfunction by spironolactone may be associated with reduction in real cardiovascular events.
The question then arose whether similar benefits might be seen in other diseases. It was therefore somewhat surprising that in a normotensive population of patients with type 2 diabetes, spironolactone actually worsened the key prognostic marker of endothelial function while also worsening glycaemic control. The situation might however be different in diabetics with poorly controlled hypertension where a spironolactone induced fall in BP might instead lead to an improvement in endothelial and autonomic function. We therefore studied whether, in patients with type 2 diabetes mellitus and poorly controlled hypertension, taking low-dose spironolactone in addition to their normal cardiovascular medication, would improve the important prognostic marker of endothelial function, as logic suggests that this should be of benefit. In addition we wish to investigate whether spironolactone treatment also brings about an improvement in the other prognostic markers of PIIINP, BNP and heart rate variability. We also wanted to see if the spironolactone induced worsening of glycaemic control that we saw in a previous study in normotensive diabetics was reproducible. |
| Design/methodology | Randomized, placebo-controlled, double-blind, cross-over design. |
| Research ethics review | The Tayside Committee for Medical Ethics, Scotland, approved on 28/09/2004 (ref: 236/03)
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| Countries of trial | United Kingdom |
| Participants - inclusion criteria | Patients with type 2 diabetes mellitus and hypertension who were on standard treatment were recruited. All patients were on either Angiotensin Converting Enzyme (ACE) inhibitors or angiotensin receptor blockers. |
| Participants - exclusion criteria | 1. Blood pressure <140 mm Hg systolic and 80 mm Hg diastolic
2. Recent admission to hospital within last 4 weeks
3. History of alcohol abuse
4. Liver or renal impairment
5. Heart failure
6. On potassium sparing diuretics, insulin or warfarin (procedural risks) |
| Patient information material |
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| Anticipated start date | 01/01/2005 |
| Anticipated end date | 31/12/2006 |
| Status of trial | Completed |
| Target number of participants | 50 |
| Interventions | In this cross-over study, each participant was treated with two different drugs and a placebo, one at a time, in addition to his or her standard medication. Each drug / placebo treatment lasted for 4 weeks, and there was a 2-week washout period between each treatment (during the washout period participants took their standard medication only). Therefore, the entire duration of the intervention was 16 weeks. Details of the intervention treatments are as follows:
1. Spironolactone, 25 mg orally per day for 1 week, increased to 50 mg per day for the next 3 weeks if potassium levels were within normal limits (total duration of treatment 4 weeks)
2. Amlodipine, 5 mg orally per day for 4 weeks
3. Placebo for 4 weeks |
| Primary outcome measure(s) | Improvement in endothelial function, assessed 24 months after the start of the trial. |
| Secondary outcome measure(s) | The following were assessed 24 months after the start of the trial:
1. Improvement in the other prognostic markers of PIIINP and B-type Natriuretic Peptide (BNP)
2. Improvement in heart rate variability |
| Sources of funding | 1. Tenovus Scotland (ref: T03/21) (UK)
2. Northwood Trust (UK) |
| Sponsor name | Tenovus Scotland (UK) |
| Sponsor details | 234 St. Vincent Street
Glasgow
United Kingdom
G2 5RJ |
| Sponsor telephone | +44 (0)1292 311276 |
| Sponsor fax | +44 (0)1292 311433 |
| Sponsor email | gen.sec@talk21.com |
| Sponsor website | http://www.tenovus-scotland.org.uk/TS_homepage.html |
| Contact name | Dr Krishnan Swaminathan |
| Contact details | Department of Clinical Pharmacology
Level 7
Ninewells Hospital
Dundee
United Kingdom
DD1 9SY |
| Contact telephone | +44 1382 632180 |
| Contact fax | +44 1382 644972 |
| Contact email | krishnan.swaminathan@nhs.net |
| More information | For more up-to-date information please go to the ISRCTN link below. |
| Link to record in ISRCTN Register | ISRCTN76558770 |
| Date last extracted from ISRCTN register | 17/04/2008 |
