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Clarifying Optimal Sodium Intake Project (COSIP-1)

Primary Purpose

Blood Pressure, Hypertension, Kidney Disease

Status
Completed
Phase
Phase 2
Locations
Ireland
Study Type
Interventional
Intervention
Sodium Reduction
Sponsored by
University College Hospital Galway
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Blood Pressure

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • HRB Clinical Research Facility Galway

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Sodium Reduction

Usual Care

Arm Description

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).

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

Outcomes

Primary Outcome Measures

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).
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).
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).
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).
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).

Secondary Outcome Measures

Change in 24-hour urinary sodium excretion
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
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
Change in eGFR (MDRD formula)
Change in eGFR (MDRD formula) from baseline to final follow-up
Change in eGFR(CKD-EPI formula)
Change in eGFR (CKD-EPI formula) from baseline to final follow-up
Change in RNA measured through PAXgene RNA blood samples
Number of recorded falls, syncope and pre-syncope
Number of cardiovascular events

Full Information

First Posted
April 4, 2016
Last Updated
April 27, 2021
Sponsor
University College Hospital Galway
Collaborators
European Research Council, National University of Ireland, Galway, Ireland
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1. Study Identification

Unique Protocol Identification Number
NCT02738736
Brief Title
Clarifying Optimal Sodium Intake Project
Acronym
COSIP-1
Official Title
Clarifying Optimal Sodium Intake Project- Objective 1
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
April 2016 (undefined)
Primary Completion Date
August 2020 (Actual)
Study Completion Date
August 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University College Hospital Galway
Collaborators
European Research Council, National University of Ireland, Galway, Ireland

4. Oversight

Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Blood Pressure, Hypertension, Kidney Disease, Cardiovascular Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
269 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sodium Reduction
Arm Type
Experimental
Arm Description
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).
Arm Title
Usual Care
Arm Type
No Intervention
Arm Description
Participants randomized to usual care will also attend a dietitian-developed healthy eating guidance session but will not receive specific recommendations targeting sodium intake.
Intervention Type
Behavioral
Intervention Name(s)
Sodium Reduction
Intervention Description
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
Primary Outcome Measure Information:
Title
Change in cardiovascular biomarkers (Renin)
Description
Change in renin from baseline to final follow-up, measured from serum measurements taken at randomisation and final visit (T8).
Time Frame
24 months
Title
Change in cardiovascular biomarkers (Aldosterone)
Description
Change in aldosterone from baseline to final follow-up, measured from serum measurements taken at randomisation and final visit (T8).
Time Frame
24 months
Title
Change in cardiovascular biomarkers (Troponin T)
Description
Change in troponin T from baseline to final follow-up, measured from serum measurements taken at randomisation and final visit (T8).
Time Frame
24 months
Title
Change in cardiovascular biomarkers (Pro-BNP)
Description
Change in Pro-BNP from baseline to final follow-up, measured from serum measurements taken at randomisation and final visit (T8).
Time Frame
24 months
Title
Change in cardiovascular biomarkers ( C-reactive protein)
Description
Change in C-reactive protein from baseline to final follow-up, measured from serum measurements taken at randomisation and final visit (T8).
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Change in 24-hour urinary sodium excretion
Description
Change in 24-hour urinary sodium excretion from baseline to final visit (two years)
Time Frame
24 months
Title
Change in mean systolic and diastolic blood pressure from 24-hour ambulatory blood pressure monitoring
Description
Change in mean systolic and diastolic blood pressure from 24-hour ambulatory blood pressure monitoring completed at baseline and final visit (two years)
Time Frame
24 months
Title
Change in functional status as measured by the assessment functional status questionnaire
Time Frame
24 months
Title
Change in eGFR (MDRD formula)
Description
Change in eGFR (MDRD formula) from baseline to final follow-up
Time Frame
24 months
Title
Change in eGFR(CKD-EPI formula)
Description
Change in eGFR (CKD-EPI formula) from baseline to final follow-up
Time Frame
24 months
Title
Change in RNA measured through PAXgene RNA blood samples
Time Frame
24 months
Title
Number of recorded falls, syncope and pre-syncope
Time Frame
24 months
Title
Number of cardiovascular events
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Martin J O'Donnell, MB PhD MRCPI
Organizational Affiliation
National University of Ireland, Galway
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Andrew Smyth, MB PhD
Organizational Affiliation
National University of Ireland, Galway
Official's Role
Principal Investigator
Facility Information:
Facility Name
HRB Clinical Research Facility Galway
City
Galway
Country
Ireland

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
36348660
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.
Results Reference
derived

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Clarifying Optimal Sodium Intake Project

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