Preventing Metabolic Side Effects of Thiazide Diuretics With KMgCitrate
1 other identifier
interventional
61
1 country
3
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for not_applicable hypertension
Started Jan 2015
Longer than P75 for not_applicable hypertension
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 1, 2015
CompletedFirst Submitted
Initial submission to the registry
January 22, 2016
CompletedFirst Posted
Study publicly available on registry
January 27, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 4, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
November 4, 2022
CompletedResults Posted
Study results publicly available
October 25, 2023
CompletedOctober 25, 2023
October 1, 2023
7.8 years
January 22, 2016
September 26, 2023
October 23, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change in Fasting Plasma Glucose From Week 4 to Week 16
Fasting plasma glucose was measured from venous blood sample at week 4 and week 16
week 4 and week 16
Secondary Outcomes (3)
Chang in Hepatic Fat Measured at Baseline and Week 16
baseline to week 16
Change in Muscle Magnesium Content Measured at Baseline and Week 16
baseline to week 16
Change in FGF23 From Week 4 to Week 16
week 4 to week 16
Study Arms (2)
KMgCit + Chlorthalidone
ACTIVE COMPARATORAfter a run-in period of 2-3 weeks on Chlorthalidone, patients will be randomized to the addition of KMgCit for 4 months.
KCl + Chlorthalidone
ACTIVE COMPARATORAfter a run-in period of 2-3 weeks on Chlorthalidone, patients will be randomized to the addition of KCl for 4 months.
Interventions
KMgCit will be administer for 4 months with chlorthalidone.
KCl will be administer for 4 months with 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.
Eligibility Criteria
You may qualify if:
- Treated or untreated stage I hypertension
You may not qualify if:
- 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,
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (3)
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, 75390, United States
University of Texas Southwestern Medical Center
Dallas, Texas, 75390, United States
UT Southwestern Medical Center
Dallas, Texas, 75390, United States
Related Publications (10)
Ahmed LA. Protective effects of magnesium supplementation on metabolic energy derangements in lipopolysaccharide-induced cardiotoxicity in mice. Eur J Pharmacol. 2012 Nov 5;694(1-3):75-81. doi: 10.1016/j.ejphar.2012.07.036. Epub 2012 Aug 23.
PMID: 22939974BACKGROUNDCarter BL, Einhorn PT, Brands M, He J, Cutler JA, Whelton PK, Bakris GL, Brancati FL, Cushman WC, Oparil S, Wright JT Jr; Working Group from the National Heart, Lung, and Blood Institute. Thiazide-induced dysglycemia: call for research from a working group from the national heart, lung, and blood institute. Hypertension. 2008 Jul;52(1):30-6. doi: 10.1161/HYPERTENSIONAHA.108.114389. Epub 2008 May 26. No abstract available.
PMID: 18504319BACKGROUNDGuerrero-Romero F, Rodriguez-Moran M. Hypomagnesemia, oxidative stress, inflammation, and metabolic syndrome. Diabetes Metab Res Rev. 2006 Nov-Dec;22(6):471-6. doi: 10.1002/dmrr.644.
PMID: 16598698BACKGROUNDHata A, Doi Y, Ninomiya T, Mukai N, Hirakawa Y, Hata J, Ozawa M, Uchida K, Shirota T, Kitazono T, Kiyohara Y. Magnesium intake decreases Type 2 diabetes risk through the improvement of insulin resistance and inflammation: the Hisayama Study. Diabet Med. 2013 Dec;30(12):1487-94. doi: 10.1111/dme.12250. Epub 2013 Jun 29.
PMID: 23758216BACKGROUNDKoenig K, Padalino P, Alexandrides G, Pak CY. Bioavailability of potassium and magnesium, and citraturic response from potassium-magnesium citrate. J Urol. 1991 Feb;145(2):330-4. doi: 10.1016/s0022-5347(17)38330-1.
PMID: 1988724BACKGROUNDOdvina CV, Mason RP, Pak CY. Prevention of thiazide-induced hypokalemia without magnesium depletion by potassium-magnesium-citrate. Am J Ther. 2006 Mar-Apr;13(2):101-8. doi: 10.1097/01.mjt.0000149922.16098.c0.
PMID: 16645424BACKGROUNDPak CY. Correction of thiazide-induced hypomagnesemia by potassium-magnesium citrate from review of prior trials. Clin Nephrol. 2000 Oct;54(4):271-5.
PMID: 11076102BACKGROUNDPrice AL, Lingvay I, Szczepaniak EW, Wiebel J, Victor RG, Szczepaniak LS. The metabolic cost of lowering blood pressure with hydrochlorothiazide. Diabetol Metab Syndr. 2013 Jul 9;5(1):35. doi: 10.1186/1758-5996-5-35.
PMID: 23837919BACKGROUNDRuml LA, Pak CY. Effect of potassium magnesium citrate on thiazide-induced hypokalemia and magnesium loss. Am J Kidney Dis. 1999 Jul;34(1):107-13. doi: 10.1016/s0272-6386(99)70115-0.
PMID: 10401023BACKGROUNDVongpatanasin W, Giacona JM, Pittman D, Murillo A, Khan G, Wang J, Johnson T, Ren J, Moe OW, Pak CCY. Potassium Magnesium Citrate Is Superior to Potassium Chloride in Reversing Metabolic Side Effects of Chlorthalidone. Hypertension. 2023 Dec;80(12):2611-2620. doi: 10.1161/HYPERTENSIONAHA.123.21932. Epub 2023 Oct 17.
PMID: 37846572DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Wanpen Vongpatanasin
- Organization
- UT Southwestern Medical Center
Study Officials
- PRINCIPAL INVESTIGATOR
Wanpen Vongpatanasin, MD
University of Texas Southwestern Medical Center
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor
Study Record Dates
First Submitted
January 22, 2016
First Posted
January 27, 2016
Study Start
January 1, 2015
Primary Completion
November 4, 2022
Study Completion
November 4, 2022
Last Updated
October 25, 2023
Results First Posted
October 25, 2023
Record last verified: 2023-10