The Effects of Sodium and Potassium on Blood Pressure, Vascular Function and Renal Function

Study Overview
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Brief Summary
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To determine the effect of (1) increased sodium intake and (2) increased potassium intake on blood pressure, vascular function and renal function in untreated (pre)hypertensive subjects.

Detailed Description
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This is a randomized, double-blind, placebo controlled cross-over feeding study.

Official Title
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Study on the Effects of Sodium and Potassium on Blood Pressure, Vascular Function and Renal Function in Untreated (Pre)Hypertensive Subjects

Conditions
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Hypertension, Blood Pressure, Vascular Function, Renal Function

Intervention / Treatment
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* Dietary Supplement: Sodium
* Drug: Potassium
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: (Pre)hypertension, defined as office SBP: 130-159 mmHg; No use of antihypertensive, lipid-lowering, anticoagulant or other cardiovascular medication; Age at start of the ≥ 40 years; Apparently healthy: No reported current or previous metabolic diseases No history of cardiovascular diseases No history of renal, liver or thyroid diseases No history of gastrointestinal diseases No diabetes mellitus Fasting laboratory parameters within normal range: renal function (serum creatinine, ureum), liver function (ALAT, ASAT, ɣ-GT) and serum glucose. Exclusion Criteria: Body mass index > 40 kg/m²; Smoking Secondary hypertension; Weight loss or weight gain of 5 kg or more during the last 2 months; Usage of non-steroidal anti-inflammatory drugs (aspirin, ibuprofen, naproxen) and not able or willing to stop taking them from at least 4 weeks prior to the study. Medical treatment that may affect blood pressure and not able (or willing) to stop taking them; Women taking oral contraceptives or estrogen replacement therapy Taking nutritional supplements and unwilling to discontinue; Women lactating, pregnant or intend to become pregnant during study; Reported dietary habits: medically prescribed diet, slimming diet; Reported alcohol consumption > 21 units/w (female subjects) or >28 units/w (male subjects); Unable or unwilling to consume one meal every workday at the university, or to consume the prescribed study diet for 13 weeks; Problems with consuming the supplements or following the study guidelines; Unwilling to undergo home or office blood pressure measurements; Recent blood donation i.e. 1 month (male subjects) or 2 months (female subjects) prior to the study and planned donation during the study period; Reported intense sporting activities > 10 h/w; Not agreeing to be informed about unexpected and medically relevant personal test-results Participation in another biomedical trial less than 2 months before the start of the study or at the same time; No informed consent signed.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sodium<br>For 4 weeks subjects will consume 3 grams of sodium by the intake of capsules on top of a low-sodium (2 grams of sodium), low-potassium (2 grams of potassium) diet | Dietary Supplement: Sodium<br>* Sodium Chloride (provided by Microz, Geleen, Netherlands): 8 capsules per day which equals a sodium intake of 3 grams.<br>|
| Active Comparator: Potassium<br>For 4 weeks subjects will consume 3 grams of potassium by the intake of capsules on top of a low-sodium (2 grams of sodium), low-potassium (2 grams of potassium) diet. | Dietary Supplement: Sodium<br>* Sodium Chloride (provided by Microz, Geleen, Netherlands): 8 capsules per day which equals a sodium intake of 3 grams.<br>Drug: Potassium<br>* Potassium Chloride (provided by Microz, Geleen, Netherlands): 8 capsules per day which equals a potassium intake of 3 grams.<br>|
| Placebo Comparator: Placebo<br>For 4 weeks subjects will consume placebo capsules (content: cellulose) on top of a low-sodium low-potassium diet | Dietary Supplement: Sodium<br>* Sodium Chloride (provided by Microz, Geleen, Netherlands): 8 capsules per day which equals a sodium intake of 3 grams.<br>Drug: Placebo<br>* Placebo (cellulose, provided by Microz, Geleen, Netherlands): 8 capsules per day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Endothelium-dependent flow-mediated dilation comparing (1) high sodium, low potassium intake and (2) low sodium, high potassium intake with low sodium, low potassium intake. | Ultra-sonography (brachial artery) + Picus system | Baseline at week 1 (t=0). After intervention period 1 at week 5 (t=1). After intervention period 2 at week 9 (t=2). After intervention period 3 at week 13 (t=3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in blood pressure comparing (1) high sodium, low potassium intake and (2) low sodium, high potassium intake with low sodium, low potassium intake. | Includes: Office BP (Dinamap, 4 consecutive measurements with 2-min intervals) ABPM (Spacelab; 1x24h, at baseline, week 5, week 9, week 13) | Screening. Baseline at week 1 (t=0). After intervention period 1 at week 5 (t=1). After intervention period 2 at week 9 (t=2). After intervention period 3 at week 13 (t=3) | 
| Change in Pulse Wave Velocity comparing (1) high sodium, low potassium intake and (2) low sodium, high potassium intake with low sodium, low potassium intake. | Device: SphygmoCor (tonometry) Parameters: Pulse Wave Velocity and at baseline, week 5, week 9 and week 13 | Baseline at week 1 (t=0). After intervention period 1 at week 5 (t=1). After intervention period 2 at week 9 (t=2). After intervention period 3 at week 13 (t=3) | 
| Change in vasomotion comparing (1) high sodium, low potassium intake and (2) low sodium, high potassium intake with low sodium, low potassium intake. | Device: PeriFlux 5000 (Perimed, Sweden0 | Baseline at week 1 (t=0). After intervention period 1 at week 5 (t=1). After intervention period 2 at week 9 (t=2). After intervention period 3 at week 13 (t=3) | 
| Change in Biomarkers of endothelial function comparing (1) high sodium, low potassium intake and (2) low sodium, high potassium intake with low sodium, low potassium intake. | Plasma analysis of endothelin-1, ADMA, MCP-1, sVCAM-1, sICAM-1, sE-selectin, sTM, CRP, SAA, IL-6, IL-8, TNF-α, vWF, nitric oxide | Baseline at week 1 (t=0). After intervention period 1 at week 5 (t=1). After intervention period 2 at week 9 (t=2). After intervention period 3 at week 13 (t=3) | 
| Change in renal function comparing (1) high sodium, low potassium intake and (2) low sodium, high potassium intake with low sodium, low potassium intake. | eGFR, serum creatinine (at screening also used as safety parameter) | Screening. Baseline at week 1 (t=0). After intervention period 1 at week 5 (t=1). After intervention period 2 at week 9 (t=2). After intervention period 3 at week 13 (t=3) | 
| Change in cardiovascular parameters in plasma comparing (1) high sodium, low potassium intake and (2) low sodium, high potassium intake with low sodium, low potassium intake. | Total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, insulin and glucose (at screening also used as safety parameter) | Screening. Baseline at week 1 (t=0). After intervention period 1 at week 5 (t=1). After intervention period 2 at week 9 (t=2). After intervention period 3 at week 13 (t=3) | 
| Liver function parameters | Montoring liver function parameters for safety: includes ALAT, ASAT and ɣ-GT | Screening. Baseline at week 1 (t=0). After intervention period 1 at week 5 (t=1). After intervention period 2 at week 9 (t=2). After intervention period 3 at week 13 (t=3) | 
| 24-hour urinary mineral excretions | Sodium and potassium (as compliance markers) | Screening. Baseline at week 1 (t=0). After intervention period 1 at week 5 (t=1). After intervention period 2 at week 9 (t=2). After intervention period 3 at week 13 (t=3) | 
| 24-hour excretion of protein, albumin and creatinine | In addition, protein is assessed in spot urine during screening using a dipstick test | Screening. Baseline at week 1 (t=0). After intervention period 1 at week 5 (t=1). After intervention period 2 at week 9 (t=2). After intervention period 3 at week 13 (t=3) | 
| Adverse events | Patient diary for occasions of illness, hospitalizations, medication use and other information on potential side effects | Every day | 
| Anthropometric measurements | Body weight (weekly), height (only at baseline), waist circumference (baseline and every 4 weeks) | Screening. Baseline at week 1 (t=0). After intervention period 1 at week 5 (t=1). After intervention period 2 at week 9 (t=2). After intervention period 3 at week 13 (t=3) | 
| Heart rate | Dinamap, 4 consecutive measurements with 2-min intervals | Screening. Baseline at week 1 (t=0). After intervention period 1 at week 5 (t=1). After intervention period 2 at week 9 (t=2). After intervention period 3 at week 13 (t=3) | 
| Food frequency questionnaire |  | Screening | 
| Change in Pulse Wave Analysis comparing (1) high sodium, low potassium intake and (2) low sodium, high potassium intake with low sodium, low potassium intake. | Device: SphygmoCor (tonometry) | Baseline at week 1 (t=0). After intervention period 1 at week 5 (t=1). After intervention period 2 at week 9 (t=2). After intervention period 3 at week 13 (t=3) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sodium, salt, potassium, blood pressure, flow-mediated dilatation, endothelial function, renal function, controlled feeding study, dietary intervention