Sodium Intake in Chronic Kidney Disease (STICK)

Sponsor

University College Hospital Galway (Other)

Overall Status

Completed

CT.gov ID

NCT02458248

Collaborator

Health Research Board, Ireland (Other), National University of Ireland, Galway, Ireland (Other)

105

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Chronic kidney disease, which affects an estimated 300,000 people in Ireland and over 50 million people in the developed world, is responsible for a considerable burden of premature mortality and morbidity. All patients with chronic kidney disease are recommended low salt diets, i.e. less than a teaspoon of salt per day (which is <5-6g of salt, which contains <2-2.3g of sodium). The average intake in the general population is double the recommended intake, between 1-2 teaspoons per day, which is considered 'moderate' intake. In patients with hypertension, reducing from moderate (average) to low intake is associated with a small reduction in blood pressure. However, achieving this low target salt intake is difficult, and can have a negative knock-on effect on other healthy dietary factors and kidney hormones. In addition, there is no convincing research to show that patients with chronic kidney disease and normal blood pressure benefit from low salt intake. In fact, the small amount of research that does exist shows that the change in kidney function is the same in people who consume low salt diets (<1 teaspoon) and moderate (1-2 teaspoons=average intake) salt diets. Moreover, there are some small studies that report that low-salt diets may increase the risk of death due to heart disease. Given that all patients with chronic kidney impairment are recommended a low-salt diet, it is important that we confirm that this recommendation truly benefits patients. In this randomized controlled trial, we hope to determine whether recommending a low salt intake, compared to average/moderate intake, is associated with a slower rate of decline in kidney function in patients with chronic kidney impairment. The results of this study will provide information to guide future research that will have critical implications for management of patients with chronic kidney disease.

Condition or Disease	Intervention/Treatment	Phase
Kidney Diseases Renal Insufficiency, Chronic Renal Insufficiency	Behavioral: Sodium Reduction	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

105 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Sodium Intake in Chronic Kidney Disease (STICK): A Randomised Controlled Trial

Study Start Date :

Mar 1, 2016

Actual Primary Completion Date :

Aug 1, 2020

Actual Study Completion Date :

Aug 1, 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 For all participants, standard care will be provided at the nephrology clinic at GUH or by local general practitioners, and includes treatment of hypertension, underlying comorbidities and optimizing the metabolic profile. Participants randomized to usual care will also attend a dietitian-developed healthy eating guidance session but will not receive specific recommendations targeting sodium intake.

Arm

Intervention/Treatment

Experimental: Sodium Reduction

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

For all participants, standard care will be provided at the nephrology clinic at GUH or by local general practitioners, and includes treatment of hypertension, underlying comorbidities and optimizing the metabolic profile. 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

Change in 24-hour urinary creatinine clearance from baseline to final follow-up, measured from 24-hour urinary collection and corresponding serum creatinine measurement at randomisation and final visit. [24 months]

Secondary Outcome Measures

Change in eGFR (MDRD formula) from baseline to final follow-up [24 months]
Change in eGFR (CKD-EPI formula) from baseline to final follow-up [24 months]
Rates of requirement for renal replacement therapy [24 months]
Change in 24-hour urinary protein from baseline to final visit [24 months]
Increase in risk category for prognosis of CKD as measured by the KDIGO 2012 CKD classification table [24 months]
Change in 24-hour urinary sodium excretion from baseline to final visit [24 months]
Change in mean systolic and diastolic blood pressure from 24-hour ambulatory blood pressure monitoring completed at baseline and final visit [24 months]
Composite outcome of change in risk category for prognosis of CKD (increase in risk), requirement for renal replacement therapy or death as measured by the KDIGO 2012 CKD classification table [24 months]
Change in functional status as measured by the assessment functional status questionnaire [24 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 40 years or older
MDRD eGFR of 30-60ml/min/1.73m2 on ≥2 occasions ≥3 months apart
Most recent eGFR measurement within 3 months 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 randomisation 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 >2.3g/day estimated from food frequency questionnaire (FFQ) completed during the screening visit
Self-reported willingness to modify dietary intake over sustained period, and adhere to directed recommendations over 2 years
Signed written informed consent

Exclusion Criteria:

Acute Kidney Injury in the preceding three months, defined as doubling of baseline serum creatinine or rapidly declining eGFR over the preceding six months, defined as a decline in eGFR of ≥10ml/min/1.73m2 in those with established CKD
Any of the following renal conditions: glomerular disease due to post-infectious glomerulonephritis, IgA nephropathy, thin basement membrane disease, Henoch-Schonlein purpura, proliferative glomerulonephritis, membranous nephropathy (including lupus nephritis), rapidly progressive glomerulonephritis, minimal change disease, or focal segmental glomerulosclerosis
Prior or planned renal transplantation
Prior, current or planned renal dialysis
Medical diagnosis known to be associated with abnormal renal sodium excretion, including Bartter syndrome, SIADH, diabetes insipidus, or serum sodium <125mmol
Severe heart failure (defined as left ventricular ejection fraction ≤30% or NYHA Class III/IV symptoms)
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
Current use of non-steroidal anti-inflammatory drugs (NSAIDs) for 3 or more days per week. Low-dose aspirin <100mg/day is not an exclusion
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 co-morbid illness or other factor (e.g. inability to travel for follow-up visits, drug or alcohol misuse) in opinion of 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) <20kg/m2 or BMI>40kg/m2
Participating in another clinical trial or previous allocation in this study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	HRB Clinical Research Facility Galway	Galway		Ireland

Sponsors and Collaborators

University College Hospital Galway
Health Research Board, Ireland
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