Preventing Metabolic Side Effects of Thiazide Diuretics With KMgCitrate

The University of Texas System (UT)

Status: Completed

Conditions: Hypertension

Treatments: Drug: Chlorthalidone; Drug: Potassium Magnesium Citrate (KMgCit); Drug: Potassium Chloride (KCl)

Study type: Interventional

Funder types: Other

Identifiers

NCT02665117

STU 092015-058

Details and patient eligibility

About

Chlorthalidone (CTD) may produce various metabolic disturbances, including hypokalemia, activation of Renin-Angiotensin- Aldosterone (RAA) system, oxidative stress, dyslipidemia, Fibroblast growth factor 23 (FGF23) synthesis, and magnesium depletion. These factors may interact with each other to contribute to the development of insulin resistances and metabolic syndrome. Smaller studies have suggested that Potassium magnesium Citrate (KMgCit) can ameliorate CTD- induced metabolic side effects independent of correction of hypokalemia. This study will tests if KMgCit ameliorates CTD induced metabolic effects independent of correction of hypokalemia.

Full description

CTD- induced metabolic side effects were though to be dependent on hypokalemia, but subsequent studies suggested that CTD - induced side effects were independent from hypokalemia. On the other hand, magnesium depletion has been linked to increased Renin-Angiotensin- Aldosterone (RAA) system, the development of metabolic syndrome and insulin resistance with magnesium supplementation ameliorating these effects.

Participants will participate in a double-blinded, parallel design study. After baseline evaluation participants will take Chlorthalidone (CTD) alone for 2-3 weeks. They will then be randomized to two equal groups to take KMgCit powder or Potassium Chloride (KCl) powder along with CTD for 4 months.

We speculate that Mg depletion is responsible for hepatic fat deposition, which then produces insulin resistance. Co-administration of KMgCit powder would avert magnesium (Mg) depletion, block hepatic fat deposition by restoring normal Mg status and direct intestinal binding of fat, thereby ameliorating insulin resistance. To test this hypothesis, we shall quantitate muscle Mg status and hepatic fat content by magnetic resonance spectroscopy (MRS) before and after KMgCit. Change in fasting glucose, insulin resistance, serum potassium, FGF23, and aldosterone will be compared between KCL and KMgCit groups after 4 months.

Enrollment: 61 patients

Sex: All

Ages: 21+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Treated or untreated stage I hypertension

Exclusion criteria

• Diabetes mellitus,
• Renal impairment (serum creatinine > 1.4 mg/dL),
• Any heart diseases such as congestive heart failure, sustained arrhythmia, or coronary heart disease,
• Chronic regular NSAID use,
• Allergy to thiazide diuretics,
• Gastro-esophageal reflux disease (GERD) requiring treatment with acid reducing agents or antacid more than once a week,
• Esophageal-gastric ulcer or history of gastrointestinal bleeding,
• Chronic diarrhea, vomiting,
• Excessive sweating,
• Unprovoked hypokalemia (serum K < 3.5 mmol/L) or hyperkalemia (serum K > 5.3 mmol/L),
• Abnormal liver function test (Aspartate transaminase (AST) or Alanine transaminase (ALT) above upper limit of normal range),
• Subjects on any potassium supplement on a regular basis for any reason, such as patients with primary aldosteronism,
• Pregnancy,
• History of major depression, bipolar disorder, or schizophrenia,
• History of substance abuse,
• Gout,
• Metabolic alkalosis, with serum bicarbonate > 32 meq/L,
• Severe dietary salt restriction, less than1/2 spoonful or 50 meq sodium/day.
• Patient with Claustrophobia will not have MRI but can still participate in the study without MRI
• Metal implants will not have MRI but can still participate in the study without MRI

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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61 participants in 2 patient groups

KMgCit + Chlorthalidone

Active Comparator group

Description:

After a run-in period of 2-3 weeks on Chlorthalidone, patients will be randomized to the addition of KMgCit for 4 months.

Treatment:

Drug: Potassium Magnesium Citrate (KMgCit)

Drug: Chlorthalidone

KCl + Chlorthalidone

Active Comparator group

Description:

After a run-in period of 2-3 weeks on Chlorthalidone, patients will be randomized to the addition of KCl for 4 months.

Treatment:

Drug: Potassium Chloride (KCl)

Drug: Chlorthalidone