Clarifying Optimal Sodium Intake Project (COSIP-1)

• ClinicalTrials.gov Identifier: NCT02738736
• Recruitment Status: Completed
• First Posted: April 14, 2016
• Last Update Posted: April 28, 2021
• Sponsor: University College Hospital Galway
• Collaborators: European Research Council; National University of Ireland, Galway, Ireland
• Information provided by (Responsible Party): Dr Andrew Smyth, University College Hospital Galway

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Blood Pressure; Hypertension; Kidney Disease; Cardiovascular Disease	Behavioral: Sodium Reduction	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 269 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Clarifying Optimal Sodium Intake Project- Objective 1
• Study Start Date: April 2016
• Actual Primary Completion Date: August 2020
• Actual Study Completion Date: August 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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).	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
No Intervention: 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.

Outcome Measures

Primary Outcome Measures :

1. Change in cardiovascular biomarkers (Renin) [ Time Frame: 24 months ]
   Change in renin from baseline to final follow-up, measured from serum measurements taken at randomisation and final visit (T8).
2. Change in cardiovascular biomarkers (Aldosterone) [ Time Frame: 24 months ]
   Change in aldosterone from baseline to final follow-up, measured from serum measurements taken at randomisation and final visit (T8).
3. Change in cardiovascular biomarkers (Troponin T) [ Time Frame: 24 months ]
   Change in troponin T from baseline to final follow-up, measured from serum measurements taken at randomisation and final visit (T8).
4. Change in cardiovascular biomarkers (Pro-BNP) [ Time Frame: 24 months ]
   Change in Pro-BNP from baseline to final follow-up, measured from serum measurements taken at randomisation and final visit (T8).
5. Change in cardiovascular biomarkers ( C-reactive protein) [ Time Frame: 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 :

1. Change in 24-hour urinary sodium excretion [ Time Frame: 24 months ]
   Change in 24-hour urinary sodium excretion from baseline to final visit (two years)
2. Change in mean systolic and diastolic blood pressure from 24-hour ambulatory blood pressure monitoring [ Time Frame: 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)
3. Change in functional status as measured by the assessment functional status questionnaire [ Time Frame: 24 months ]
4. Change in eGFR (MDRD formula) [ Time Frame: 24 months ]
   Change in eGFR (MDRD formula) from baseline to final follow-up
5. Change in eGFR(CKD-EPI formula) [ Time Frame: 24 months ]
   Change in eGFR (CKD-EPI formula) from baseline to final follow-up
6. Change in RNA measured through PAXgene RNA blood samples [ Time Frame: 24 months ]
7. Number of recorded falls, syncope and pre-syncope [ Time Frame: 24 months ]
8. Number of cardiovascular events [ Time Frame: 24 months ]

Eligibility Criteria

• Ages Eligible for Study: 40 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

Ireland

HRB Clinical Research Facility Galway

Galway, Ireland

Sponsors and Collaborators

University College Hospital Galway

European Research Council

National University of Ireland, Galway, Ireland

Investigators

• Principal Investigator: Martin J O'Donnell, MB PhD MRCPI; National University of Ireland, Galway
• Principal Investigator: Andrew Smyth, MB PhD; National University of Ireland, Galway

More Information

• Responsible Party: Dr Andrew Smyth, Dr., University College Hospital Galway
• ClinicalTrials.gov Identifier: NCT02738736
• Other Study ID Numbers: HRBCRFG-010416
• First Posted: April 14, 2016
• Last Update Posted: April 28, 2021
• Last Verified: April 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

Kidney Diseases; Cardiovascular Diseases; Urologic Diseases