The renin-angiotensin-aldosterone (RAAS) axis, endothelial function and hypertension: diagnostic strategies, and therapeutic role of potassium supplementation
| ISRCTN | ISRCTN55798944 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN55798944 |
| Secondary identifying numbers | RGHT000502 |
- Submission date
- 25/03/2009
- Registration date
- 30/06/2009
- Last edited
- 30/12/2020
- 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
Dr Karen Mullan
Scientific
Scientific
Royal Victoria Hospital
Grosvenor Road
Belfast
BT12 6BA
United Kingdom
Study information
| Study design | Study 1: Prospective randomised cross-over investigator-blinded trial Study 2: Observational study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Prevention |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | The renin-angiotensin-aldosterone (RAAS) axis, endothelial function and hypertension: diagnostic strategies, and therapeutic role of potassium supplementation - a randomised cross-over trial and an observational study |
| Study objectives | Study 1: We seek to test the hypothesis that endothelial function is improved when dietary potassium is supplemented in a group with moderate risk of developing cardiovascular disease. We also wish to assess the effect of this supplementation on the renin-angiotensin-aldosterone (RAAS) axis and the effect of any of these changes on proinflammatory cytokines and adhesion molecules. Study 2: We seek to test the hypothesis that the synacthen test can be used to distinguish patients with primary (essential) hypertension from those with secondary hypertension due to hyperaldosteronism (due to Conn's adenoma or bilateral adrenalhyperplasia). We will also assess the aldosterone response to gonadotropin releasing hormone (GnRH) in healthy volunteers and patients with hyperaldosteronism. |
| Ethics approval(s) | Office for Research Ethics Committees Northern Ireland Study 1 approved on 02/09/2008 (ref. 08/NIR08/54) Study 2 approved on 19/08/2008 (ref. 08/NIR08/55) |
| Health condition(s) or problem(s) studied | Hypertension, cardiovascular risk, hyperaldosteronism |
| Intervention | Study 1: Dietary intake of sodium and potassium will be assessed and a 24 hour urine collection for estimation of Na and K excretion will be taken. The subjects will be randomised to either placebo or potassium supplementation (4.8 g/day; oral) for 6 weeks. There will be a 6 week washout period. Subjects will be studied at baseline, at the end of washout and after each intervention (4 in total). Study 2: The target numbers of participants for the three groups are as follows: i. Patients with essential hypertension: n = 20 ii. Patients with hyperaldosteronism: n = 8 iii. Healthy volunteers: n = 15 43 participants in total Patients with essential hypertension and patients with hyperaldosteronism will undergo a 250 mcg synacthen test with blood and saliva sampled at 0, 30 and 60 mins for cortisol and aldosterone. This test will be performed after 30 min of recumbency. In addition the healthy volunteers and patients with hyperaldosteronism will also undergo a GnRH test to assess aldosterone response. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Potassium |
| Primary outcome measure | Study 1 - Global endothelial function assessed by determining the change in augmentation index (AIx) in response to the administration of nitroglycerin (NTG) and salbutamol. Study 2 - Aldosterone response to synacthen/GnRH All primary and secondary outcomes for Study 1 will be assessed at baseline, at the end of washout and after each intervention. |
| Secondary outcome measures | Study 1 - Brachial blood pressure, pulse wave velocity, serum potassium, renal function, lipid profile, plasma renin activity and aldosterone levels (taken after at least 30 minutes recumbency). Circulating markers of endothelial function (E selectin, VCAM-1, ICAM-1) and markers of inflammation (IL-6, IL-1 beta, hsCRP) All primary and secondary outcomes for Study 1 will be assessed at baseline, at the end of washout and after each intervention. |
| Overall study start date | 20/11/2008 |
| Completion date | 06/08/2010 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 70 Years |
| Sex | Both |
| Target number of participants | 83 (Study 1: 40, Study 2: 43) |
| Total final enrolment | 40 |
| Key inclusion criteria | Study 1: 1.1. Patients (both males and females) aged 40-70 with moderate (>10%) cardiovascular disease risk (Joint British Societies' [JSB2] guidelines) Study 2: Three groups of participants (both males and females, all within age 18-70): 2.1. Patients with essential hypertension 2.2. Patients with hyperaldosteronism 2.3. Healthy volunteers |
| Key exclusion criteria | Study 1: 1.1. A history or renal or cardiovascular disease 1.2. Fasting glucose >7 mmol/l 1.3. Serum potassium >5.5 mmol/l 1.4. Treated seated blood pressure >140/90 mmHg 1.5. Women on hormone replacement therapy (HRT) 1.6. Pregnancy Study 2: 2.1. Pregnancy |
| Date of first enrolment | 20/11/2008 |
| Date of final enrolment | 06/08/2010 |
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
Royal Victoria Hospital (UK)
Hospital/treatment centre
Hospital/treatment centre
Grosvenor Road
Belfast
BT12 6BA
Northern Ireland
United Kingdom
| Website | http://www.belfasttrust.hscni.net/ |
|---|---|
"ROR" |
https://ror.org/03rq50d77 |
Funders
Funder type
Government
Northern Ireland Research and Development Office (UK) (ref: EAT/3740/07)
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 | 01/05/2014 | 30/12/2020 | Yes | No |
Editorial Notes
30/12/2020: The following changes have been made:
1. Publication reference added.
2. The final enrolment number has been added from the reference.
12/07/2016: No publications found, verifying study status with principal investigator.
