Preventing Metabolic Side Effects of Thiazide Diuretics With KMgCitrate

Not Applicable

Completed

• Conditions: Hypertension
• Interventions: Drug: Potassium Magnesium Citrate (KMgCit); Drug: Potassium Chloride (KCl); Drug: Chlorthalidone

• Registration Number: NCT02665117
• Lead Sponsor: University of Texas Southwestern Medical Center

Brief Summary

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.

Detailed 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.

Study Timeline

• Study Start: 2015-01
• Study First Submitted: 2016-01-22
• Study First Submitted QC: 2016-01-26
• Study First Posted: 2016-01-27
• Primary Completion: 2022-11-04
• Study Completion: 2022-11-04
• Results First Submitted: 2023-09-26
• Status Verified: 2023-10
• Results First Submitted QC: 2023-10-23
• Last Update Submitted: 2023-10-23
• Results First Posted: 2023-10-25
• Last Update Posted: 2023-10-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 61

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
KMgCit + Chlorthalidone	Potassium Magnesium Citrate (KMgCit)	After a run-in period of 2-3 weeks on Chlorthalidone, patients will be randomized to the addition of KMgCit for 4 months.
KCl + Chlorthalidone	Potassium Chloride (KCl)	After a run-in period of 2-3 weeks on Chlorthalidone, patients will be randomized to the addition of KCl for 4 months.
KMgCit + Chlorthalidone	Chlorthalidone	After a run-in period of 2-3 weeks on Chlorthalidone, patients will be randomized to the addition of KMgCit for 4 months.
KCl + Chlorthalidone	Chlorthalidone	After a run-in period of 2-3 weeks on Chlorthalidone, patients will be randomized to the addition of KCl for 4 months.

Primary Outcome Measures

Name	Time	Method
Change in Fasting Plasma Glucose From Week 4 to Week 16	week 4 and week 16	Fasting plasma glucose was measured from venous blood sample at week 4 and week 16

Secondary Outcome Measures

Name	Time	Method
Change in FGF23 From Week 4 to Week 16	week 4 to week 16	Will be measured from venous blood sample from week 4 to week 16
Change in Muscle Magnesium Content Measured at Baseline and Week 16	baseline to week 16	Will be measured using magnetic resonance imaging at baseline and at week 16
Chang in Hepatic Fat Measured at Baseline and Week 16	baseline to week 16	Will be measured using hepatic magnetic resonance imaging at baseline and at week 16

Trial Locations

Locations (3)

University of Texas Southwestern Medical Center at Dallas; 🇺🇸 Dallas, Texas, United States

UT Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

University of Texas Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States