Value of Liquid Potassium Magnesium Citrate in Controlling Hypertension

Study Overview
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Brief Summary
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In the DASH (Dietary Approaches to Stop Hypertension) trials, a diet rich in fruits, vegetables, nuts and dairy products, and limited in fat content, was shown to be useful in controlling hypertension. Key components of such a diet are potassium, magnesium and alkali, each of which has been implicated in lowering blood pressure. Whether a liquid formulation of potassium-magnesium citrate will result in equivalent BP effect as the DASH diet is unknown.

Detailed Description
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The DASH diet is rich in potassium and magnesium. It is also high in alkali content, since the anions are provided mostly by citrate rather than chloride. Considerable data are already available in the literature invoking a protective role on hypertension of potassium, magnesium and alkali. In this protocol, the investigators want to test the hypothesis that liquid potassium-magnesium citrate (KMgCit) as a pharmaceutical formulation could serve as a surrogate for the DASH diet, and would lower blood pressure among patients with pre- or Stage I hypertension on their customary diet. Each subject will participate in all four phases, chosen in random order. The four phases will be: Placebo Phase (microcrystalline cellulose in water), Potassium Chloride Phase (potassium chloride powder in water), Potassium Citrate Phase (potassium citrate powder in water), KMgCit Phase (KMgCit powder in water) During each phase, subjects will receive one of the test drugs for 4 weeks, followed by at least 1 week of withdrawal. Change in 24 hr BP, office BP will be measured at baseline and after each phase. Central aortic blood pressure and carotid-femoral pulse wave velocity, -terminal-telopeptide (CTX), 24 hr urine electrolytes will be measured at 4 weeks in each phase.

Official Title
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Value of Liquid Potassium Magnesium Citrate in Controlling Hypertension

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Potassium chloride powder
* Drug: Potassium magnesium Citrate (KMgCit)
* Drug: Potassium citrate powder
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with pre- or Stage I hypertension, with systolic blood pressure of 120-159 mm and diastolic of 80-99 mm Age > 21 years of age Exclusion Criteria: Diabetes mellitus, Renal impairment (serum creatinine > 1.4 mg/dL), Any heart diseases such as congestive heart failure or sustained arrhythmia, Chronic NSAID use, Treatment with diuretics, Gastroesophageal reflux disease (GERD) requiring treatment with acid reducing agents or antacid more than once a week, Esophageal-gastric ulcer, Chronic diarrhea Hyperkalemia (serum > 4.6 mmol/L for patients on Angiotensin converting enzyme (ACE) inhibitors or Angiotensin receptor blockers (ARB), serum K > 5.0 for patient not on ACE inhibitors or ARBs) Liver function test above upper limit of normal range. Subjects who require any potassium supplement on a regular basis from any reasons Pregnancy History of major depression, bipolar disorder, or schizophrenia History of substance abuse.

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Potassium magnesium Citrate (KMgCit) arm<br>Potassium magnesium citrate will be prepared by mixing potassium citrate, magnesium citrate and/or citric acid by Meta Pharm Development. The content of each sachet will be dissolved in 250 ml water and will be drunk with breakfast and again with dinner during the KMgCit Phase, to deliver 40 meq K, 20 meq Mg and 74 meq citrate per day for 4 weeks | Drug: Potassium magnesium Citrate (KMgCit)<br> <br> |
| Experimental: Potassium citrate arm<br>A special sachet formulation containing 20 meq K/sachet will be made for the study by Meta Pharm Development. The contents of a sachet will be added to 250 ml water and drunk with breakfast and dinner, to deliver 40 meq K (as citrate) per day during the Potassium Citrate Phase for 4 weeks. | Drug: Potassium citrate powder<br> <br> * Other names: Urocit®-K powder;|
| Experimental: Potassium chloride arm<br>Potassium chloride will contain 20 meq KCl per sachet. During the Potassium Chloride Phase, subjects will dissolve the content of each sachet in 250 ml water and ingest it with breakfast and again with dinner, to deliver 40 meq K (as chloride) per day for 4 weeks | Drug: Potassium chloride powder<br> <br> |
| Placebo Comparator: Placebo<br>Placebo will comprise microcrystalline cellulose, equivalent in volume in each sachet as other test products. During the Placebo Phase, subjects will dissolve the entire content of a sachet in 250 ml water and drink it with breakfast and again with dinner for 4 weeks. | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24-hour Average Systolic Blood Pressure | Systolic blood pressure was measured through an ambulatory blood pressure monitoring device worn by each participant for 24 hours after completing each treatment phase. This devise measures blood pressure intermittently throughout the day and night and provides the average of all readings. | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Citrate, Potassium, Magnesium, DASH