Clarifying Optimal Sodium Intake Project

NCT02738736 | Completed Phase 2 DMC

• 1 other identifier: HRBCRFG-010416
• Study Type: interventional
• Target: 269
• Locations: 1 country
• Sites: 1

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.

Conditions

Blood Pressure; Hypertension; Kidney Disease; Cardiovascular Disease

Outcome Measures

Primary Outcomes (5)

• 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

• 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

• 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

• 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

• 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 Outcomes (8)

• Change in 24-hour urinary sodium excretion

  24 months

• Change in mean systolic and diastolic blood pressure from 24-hour ambulatory blood pressure monitoring

  24 months

• Change in functional status as measured by the assessment functional status questionnaire

  24 months

• Change in eGFR (MDRD formula)

  24 months

• Change in eGFR(CKD-EPI formula)

  24 months

Study Arms (2)

Sodium Reduction

EXPERIMENTAL

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).

Behavioral: Sodium Reduction

Usual Care

NO INTERVENTION

Participants randomized to usual care will also attend a dietitian-developed healthy eating guidance session but will not receive specific recommendations targeting sodium intake.

Interventions

Sodium Reduction BEHAVIORAL

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

Sodium Reduction

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• University College Hospital Galway: lead
• European Research Council: collaborator
• National University of Ireland, Galway, Ireland: collaborator

Study Sites (1)

HRB Clinical Research Facility Galway

Galway, Ireland

Location

Related Publications (2)

• Smyth A, Judge C, Kerins C, McDermott S, Niland A, Corcoran C, Dineen R, Alvarez-Iglesias A, Nolan A, Mente A, Griffin MD, O'Shea P, Canavan M, Yusuf S, O'Donnell M. Dietary counselling to reduce moderate sodium intake: effects on cardiovascular and renal biomarkers: primary findings of the COSIP and STICK phase II feasibility randomised controlled trials. EClinicalMedicine. 2023 Feb 15;57:101856. doi: 10.1016/j.eclinm.2023.101856. eCollection 2023 Mar.

  PMID: 37064508 DERIVED

• Smyth A, Yusuf S, Kerins C, Corcoran C, Dineen R, Alvarez-Iglesias A, Ferguson J, McDermott S, Hernon O, Ranjan R, Nolan A, Griffin M, O'Shea P, Canavan M, O'Donnell M. Clarifying Optimal Sodium InTake In Cardiovasular and Kidney (COSTICK) Diseases: a study protocol for two randomised controlled trials. HRB Open Res. 2022 Feb 7;4:14. doi: 10.12688/hrbopenres.13210.2. eCollection 2021.

  PMID: 36348660 DERIVED

MeSH Terms

Conditions

Hypertension; Kidney Diseases; Cardiovascular Diseases

Condition Hierarchy (Ancestors)

Vascular Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Martin J O'Donnell, MB PhD MRCPI

  National University of Ireland, Galway

  PRINCIPAL INVESTIGATOR

• Andrew Smyth, MB PhD

  National University of Ireland, Galway

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.

Study Record Dates

• First Submitted: April 4, 2016
• First Posted: April 14, 2016
• Study Start: April 1, 2016
• Primary Completion: August 1, 2020
• Study Completion: August 1, 2020
• Last Updated: April 28, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

IE (1)