Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
RGHT000502
Study information
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
Acronym
Study hypothesis
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
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)
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
Trial setting
Hospitals
Trial type
Prevention
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
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
Phase
Not Applicable
Drug names
Potassium
Primary outcome measures
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 trial start date
20/11/2008
Overall trial end date
06/08/2010
Reason abandoned
Eligibility
Participant 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
Participant type
Healthy volunteer
Age group
Adult
Gender
Both
Target number of participants
83 (Study 1: 40, Study 2: 43)
Participant 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
Recruitment start date
20/11/2008
Recruitment end date
06/08/2010
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Royal Victoria Hospital
Belfast
BT12 6BA
United Kingdom
Sponsor information
Organisation
Royal Victoria Hospital (UK)
Sponsor details
Grosvenor Road
Belfast
BT12 6BA
United Kingdom
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Government
Funder name
Northern Ireland Research and Development Office (UK) (ref: EAT/3740/07)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
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