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

Royal Victoria Hospital
Grosvenor Road
Belfast
BT12 6BA
United Kingdom

Study information

Study designStudy 1: Prospective randomised cross-over investigator-blinded trial Study 2: Observational study
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typePrevention
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific titleThe 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 objectivesStudy 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) studiedHypertension, cardiovascular risk, hyperaldosteronism
InterventionStudy 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 typeDrug
Pharmaceutical study type(s)
PhaseNot Applicable
Drug / device / biological / vaccine name(s)Potassium
Primary outcome measureStudy 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 measuresStudy 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 date20/11/2008
Completion date06/08/2010

Eligibility

Participant type(s)Healthy volunteer
Age groupAdult
Lower age limit18 Years
Upper age limit70 Years
SexBoth
Target number of participants83 (Study 1: 40, Study 2: 43)
Total final enrolment40
Key inclusion criteriaStudy 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 criteriaStudy 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 enrolment20/11/2008
Date of final enrolment06/08/2010

Locations

Countries of recruitment

  • Northern Ireland
  • United Kingdom

Study participating centre

Royal Victoria Hospital
Belfast
BT12 6BA
United Kingdom

Sponsor information

Royal Victoria Hospital (UK)
Hospital/treatment centre

Grosvenor Road
Belfast
BT12 6BA
Northern Ireland
United Kingdom

Website http://www.belfasttrust.hscni.net/
ROR logo "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 shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot 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.