Clarifying Optimal Sodium Intake Project

NCT ID: NCT02738736

Last Updated: 2021-04-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 269 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-04-30
• Study Completion Date: 2020-08-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

Sodium Reduction

Intervention Type: 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

Usual Care

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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

Intervention Type: BEHAVIORAL

Eligibility Criteria

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

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

European Research Council

OTHER

Sponsor Role: collaborator

National University of Ireland, Galway, Ireland

OTHER

Sponsor Role: collaborator

University College Hospital Galway

OTHER

Sponsor Role: lead

Responsible Party

Dr Andrew Smyth

Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Martin J O'Donnell, MB PhD MRCPI

Role: PRINCIPAL_INVESTIGATOR

National University of Ireland, Galway

Andrew Smyth, MB PhD

Role: PRINCIPAL_INVESTIGATOR

National University of Ireland, Galway

Locations

HRB Clinical Research Facility Galway

Galway, , Ireland

Countries

Ireland

References

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.

Reference Type: DERIVED

PMID: 37064508 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36348660 (View on PubMed)

Other Identifiers

HRBCRFG-010416

Identifier Type: -

Identifier Source: org_study_id