Clarifying Optimal Sodium Intake Project

Hypertension Clinical Trial

— COSIP-1  

Official title:

Clarifying Optimal Sodium Intake Project- Objective 1

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02738736
• Other study ID #: HRBCRFG-010416
• Status: Completed
• Phase: Phase 2
• Start date: April 2016
• Est. completion date: August 2020

Study information

• Verified date: April 2021
• Source: University College Hospital Galway
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Hypertension is a leading risk factor for cardiovascular disease (CVD) globally, accounting for 25-35% of the population-attributable fraction. Sodium (salt) intake is a key determinant of blood pressure, and reducing sodium intake has emerged as an important target for population-based interventions to prevent CVD. However, there is considerable uncertainty about the optimal level of sodium intake that is associated with lowest CV risk, and whether optimal levels differ for different populations and individuals. International and national guidelines recommend low sodium intake (<2.3g/day, or lower) in all persons, and advocate a population-wide approach to reducing sodium. Most of the world's population (~95%) consume between 3 and 6g/day of sodium (mean intake 4.0g/day), which means that most people will require a major change to their diet, to achieve the guideline target (<2g/day). While there is convincing evidence that high sodium intake (>5g/day) is associated with an increased risk of CVD, compared to low or moderate intake, the evidence that low sodium intake (<2.0g/day) is associated with a lower risk of CVD than moderate intake (2.0-5g/day) is inconsistent and inconclusive. The investigators plan to conduct a Phase IIb clinical trial to evaluate the role of low sodium intake (versus moderate) on cardiovascular biomarkers.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 269
• Est. completion date: August 2020
• Est. primary completion date: August 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Age 40 years or older

• Systolic blood pressure <160mmHg and diastolic blood pressure <95mmHg on three office blood pressure readings at time of screening and confirmed by a study ABPM before randomization of <150/90mmHg

• No change in anti-hypertensive or diuretic medications (including dose) for 3 months before screening visit

• Consumption of moderate sodium intake at screening, defined as an estimated daily sodium intake of >2.3/day estimated from food frequency questionnaire (FFQ)

• Self-reported willingness to modify dietary intake over sustained period, and adhere with directed recommendations over 2 years.

• Signed written informed consent

Exclusion Criteria:

• Known chronic kidney disease (CKD) or most recent eGFR =60ml/min/1.73m2

• Participants who are ineligible for COSIP based on their eGFR will be approached about entering the ongoing Sodium Intake in Chronic Kidney Disease (STICK) trial.

• Previous cardiovascular disease:

• Myocardial infarction

• Previous percutaneous coronary intervention (PCI) or percutaneous transluminal coronary angioplasty (PTCA)

• Stroke (previous transient ischaemic attack [TIA] is not an exclusion criterion)

• Medical diagnosis known to be associated with abnormal renal sodium excretion, including the following:

• Bartter syndrome

• SIADH

• Diabetes insipidus

• Serum sodium <125mmol

• Severe heart failure defined as NYHA Class III/IV OR left ventricular ejection fraction (LVEF) =30%

• High-dose loop or thiazide diuretic therapy, exceeding a total daily dose of frusemide 80mg, bumetanide 2mg, hydrochlorothiazide 50mg, bendroflumethiazide 2.5mg, indapamide 2.5mg, metolazone 2.5mg or the use of both a loop and thiazide diuretic

• Unable to follow educational advice of the research team

• Prescribed high-salt diet, low-salt diet or sodium bicarbonate

• Symptomatic postural hypotension or receiving treatment for postural hypotension

• Current or recent use (within one month) of immunosuppressive medications including tacrolimus, cyclosporine, azathioprine or mycophenolate mofetil

• Pregnancy or lactation

• Unable to comply with 24-hour urinary collections, or medical condition making collection of 24-hour urinary collection difficult (e.g. severe urinary incontinence)

• Participant unlikely to comply with study procedures or follow-up visits due to severe comorbid illness or other factor (e.g. inability to travel for follow-up visits, drug or alcohol misuse) in the opinion of the research team

• Cognitive impairment defined as a known diagnosis of dementia or inability to provide informed consent due to cognitive impairment in the opinion of the investigator

• Body Mass Index (BMI) <20 kg/m2 or BMI>40 kg/m2

• Participating in another clinical trial or previous allocation in this study

Related Conditions & MeSH terms

• Blood Pressure
• Cardiovascular Disease
• Cardiovascular Diseases
• Hypertension
• Kidney Disease
• Kidney Diseases

Intervention

Behavioral:
• Sodium Reduction
In addition to usual care, those randomised to the intervention arm will receive specific counseling on behavioural and environmental factors that promote sodium reduction after randomization and at all specified post-randomisation visits, targeting sodium intake of <100mmol/day (<2.3g/day). A research dietitian will develop the specific components of the intervention, based on standardised approaches to education interventions

Locations

Country	Name	City	State
Ireland	HRB Clinical Research Facility Galway	Galway

Sponsors (3)

Lead Sponsor	Collaborator
University College Hospital Galway	European Research Council, National University of Ireland, Galway, Ireland

Country where clinical trial is conducted

Ireland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in cardiovascular biomarkers (Renin)	Change in renin from baseline to final follow-up, measured from serum measurements taken at randomisation and final visit (T8).	24 months
Primary	Change in cardiovascular biomarkers (Aldosterone)	Change in aldosterone from baseline to final follow-up, measured from serum measurements taken at randomisation and final visit (T8).	24 months
Primary	Change in cardiovascular biomarkers (Troponin T)	Change in troponin T from baseline to final follow-up, measured from serum measurements taken at randomisation and final visit (T8).	24 months
Primary	Change in cardiovascular biomarkers (Pro-BNP)	Change in Pro-BNP from baseline to final follow-up, measured from serum measurements taken at randomisation and final visit (T8).	24 months
Primary	Change in cardiovascular biomarkers ( C-reactive protein)	Change in C-reactive protein from baseline to final follow-up, measured from serum measurements taken at randomisation and final visit (T8).	24 months
Secondary	Change in 24-hour urinary sodium excretion	Change in 24-hour urinary sodium excretion from baseline to final visit (two years)	24 months
Secondary	Change in mean systolic and diastolic blood pressure from 24-hour ambulatory blood pressure monitoring	Change in mean systolic and diastolic blood pressure from 24-hour ambulatory blood pressure monitoring completed at baseline and final visit (two years)	24 months
Secondary	Change in functional status as measured by the assessment functional status questionnaire		24 months
Secondary	Change in eGFR (MDRD formula)	Change in eGFR (MDRD formula) from baseline to final follow-up	24 months
Secondary	Change in eGFR(CKD-EPI formula)	Change in eGFR (CKD-EPI formula) from baseline to final follow-up	24 months
Secondary	Change in RNA measured through PAXgene RNA blood samples		24 months
Secondary	Number of recorded falls, syncope and pre-syncope		24 months
Secondary	Number of cardiovascular events		24 months