Preventing Metabolic Side Effects of Thiazide Diuretics With KMgCitrate

October 23, 2023 updated by: Wanpen Vongpatanasin, University of Texas Southwestern Medical Center
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

61

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Dallas, Texas, United States, 75390
        • University of Texas Southwestern Medical Center
      • Dallas, Texas, United States, 75390
        • UT southwestern Medical Center
      • Dallas, Texas, United States, 75390
        • University Of Texas Southwestern Medical Center At Dallas

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: KMgCit + Chlorthalidone
After a run-in period of 2-3 weeks on Chlorthalidone, patients will be randomized to the addition of KMgCit for 4 months.
Drug: Potassium Magnesium Citrate (KMgCit)
KMgCit will be administer for 4 months with chlorthalidone.
Other Names:
  • KMgCit
Drug: Chlorthalidone
Chlorthalidone will be administered for 2-3 weeks. Then either KCL or KMgCit will be added to Chlorthalidone and the combination will be taken for 4 months.
Active Comparator: KCl + Chlorthalidone
After a run-in period of 2-3 weeks on Chlorthalidone, patients will be randomized to the addition of KCl for 4 months.
Drug: Chlorthalidone
Chlorthalidone will be administered for 2-3 weeks. Then either KCL or KMgCit will be added to Chlorthalidone and the combination will be taken for 4 months.
Drug: Potassium Chloride (KCl)
KCl will be administer for 4 months with chlorthalidone.
Other Names:
  • KCl

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Fasting Plasma Glucose From Week 4 to Week 16
Time Frame: week 4 and week 16
Fasting plasma glucose was measured from venous blood sample at week 4 and week 16
week 4 and week 16

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Texas Southwestern Medical Center

Investigators

  • Principal Investigator: Wanpen Vongpatanasin, MD, UT southwestern Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2015

Primary Completion (Actual)

November 4, 2022

Study Completion (Actual)

November 4, 2022

Study Registration Dates

First Submitted

January 22, 2016

First Submitted That Met QC Criteria

January 26, 2016

First Posted (Estimated)

January 27, 2016

Study Record Updates

Last Update Posted (Actual)

October 25, 2023

Last Update Submitted That Met QC Criteria

October 23, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STU 092015-058

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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