Clinical trial NCT02738736: Clarifying Optimal Sodium Intake Project
Official title: Clarifying Optimal Sodium Intake Project- Objective 1
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Blood Pressure
Hypertension
Kidney Disease
Cardiovascular Disease
Lead sponsor: University College Hospital Galway
Sponsor class: OTHER
Collaborators: name: European Research Council
name: National University of Ireland, Galway, Ireland
First posted: 2016-04-14
Enrollment: 269
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change in cardiovascular biomarkers (Renin)
timeFrame: 24 months
measure: Change in cardiovascular biomarkers (Aldosterone)
timeFrame: 24 months
measure: Change in cardiovascular biomarkers (Troponin T)
timeFrame: 24 months
measure: Change in cardiovascular biomarkers (Pro-BNP)
timeFrame: 24 months
measure: Change in cardiovascular biomarkers ( C-reactive protein)
timeFrame: 24 months
Secondary outcomes:
measure: Change in 24-hour urinary sodium excretion
timeFrame: 24 months
measure: Change in mean systolic and diastolic blood pressure from 24-hour ambulatory blood pressure monitoring
timeFrame: 24 months
measure: Change in functional status as measured by the assessment functional status questionnaire
timeFrame: 24 months
measure: Change in eGFR (MDRD formula)
timeFrame: 24 months
measure: Change in eGFR(CKD-EPI formula)
timeFrame: 24 months
measure: Change in RNA measured through PAXgene RNA blood samples
timeFrame: 24 months
measure: Number of recorded falls, syncope and pre-syncope
timeFrame: 24 months
measure: Number of cardiovascular events
timeFrame: 24 months
Other outcomes:
Locations:
city: Galway
country: Ireland
facility: HRB Clinical Research Facility Galway
Study officials:
affiliation: National University of Ireland, Galway
name: Martin J O'Donnell, MB PhD MRCPI
role: PRINCIPAL_INVESTIGATOR
affiliation: National University of Ireland, Galway
name: Andrew Smyth, MB PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.