Clarifying Optimal Sodium Intake Project

Phase 2

Completed

• Conditions: Hypertension; Kidney Disease; Cardiovascular Disease; Blood Pressure
• Interventions: Behavioral: Sodium Reduction

• Registration Number: NCT02738736
• Lead Sponsor: University College Hospital Galway

Brief 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-04
• Study First Submitted: 2016-04-04
• Study First Submitted QC: 2016-04-13
• Study First Posted: 2016-04-14
• Primary Completion: 2020-08
• Study Completion: 2020-08
• Status Verified: 2021-04
• Last Update Submitted: 2021-04-27
• Last Update Posted: 2021-04-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 269

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sodium Reduction	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 post-randomisation visits, targeting sodium intake of \<100mmol/day (\<2.3g/day).

Primary Outcome Measures

Name	Time	Method
Change in cardiovascular biomarkers (Renin)	24 months	Change in renin from baseline to final follow-up, measured from serum measurements taken at randomisation and final visit (T8).
Change in cardiovascular biomarkers (Aldosterone)	24 months	Change in aldosterone from baseline to final follow-up, measured from serum measurements taken at randomisation and final visit (T8).
Change in cardiovascular biomarkers (Troponin T)	24 months	Change in troponin T from baseline to final follow-up, measured from serum measurements taken at randomisation and final visit (T8).
Change in cardiovascular biomarkers (Pro-BNP)	24 months	Change in Pro-BNP from baseline to final follow-up, measured from serum measurements taken at randomisation and final visit (T8).
Change in cardiovascular biomarkers ( C-reactive protein)	24 months	Change in C-reactive protein from baseline to final follow-up, measured from serum measurements taken at randomisation and final visit (T8).

Secondary Outcome Measures

Name	Time	Method
Change in 24-hour urinary sodium excretion	24 months	Change in 24-hour urinary sodium excretion from baseline to final visit (two years)
Change in mean systolic and diastolic blood pressure from 24-hour ambulatory blood pressure monitoring	24 months	Change in mean systolic and diastolic blood pressure from 24-hour ambulatory blood pressure monitoring completed at baseline and final visit (two years)
Change in functional status as measured by the assessment functional status questionnaire	24 months
Change in eGFR (MDRD formula)	24 months	Change in eGFR (MDRD formula) from baseline to final follow-up
Change in eGFR(CKD-EPI formula)	24 months	Change in eGFR (CKD-EPI formula) from baseline to final follow-up
Change in RNA measured through PAXgene RNA blood samples	24 months
Number of recorded falls, syncope and pre-syncope	24 months
Number of cardiovascular events	24 months

Trial Locations

Locations (1)

HRB Clinical Research Facility Galway; 🇮🇪 Galway, Ireland