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HypertensionNCT02665117

Preventing Metabolic Side Effects of Thiazide Diuretics With KMgCitrate

A study testing Potassium Magnesium Citrate (KMgCit), Potassium Chloride (KCl) and Chlorthalidone in people with Hypertension, run by University of Texas Southwestern Medical Center at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 21 years and older
Conditions the study is for
Hypertension
What is being tested?
Potassium Magnesium Citrate (KMgCit), Potassium Chloride (KCl) and Chlorthalidone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
61 participants
Where
3 sitesUnited States
Study dates
Jan 2015to 4 Nov 2022
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Treated or untreated stage I hypertension

Who cannot join

  • 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,
Show all 20Show fewer
  • 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 locations and contacts

3 sites in 1 country.

United States3 sites

  • University of Texas Southwestern Medical Center at Dallas

    Dallas, Texas, 75390

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • UT Southwestern Medical Center

    Dallas, Texas, 75390

Other trials in United States

About this study

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.

Read the 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.

Conditions
Hypertension
Being tested
Potassium Magnesium Citrate (KMgCit), Potassium Chloride (KCl), Chlorthalidone
Keywords
Hypokalemia, Isoprostanes, Insulin resistance, Aldosterone, Hepatic fat, Muscle Magnesium, Liver fat
Medical subject headings
Hypertension, Hypokalemia, Insulin Resistance, Fatty Liver

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Potassium Magnesium Citrate (KMgCit)Drug

    Also called KMgCit

    KMgCit will be administer for 4 months with chlorthalidone.

  • Potassium Chloride (KCl)Drug

    Also called KCl

    KCl will be administer for 4 months with chlorthalidone.

  • ChlorthalidoneDrug

    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.

Study groups in NCT02665117
Study groupRoleWhat they receive
KMgCit + ChlorthalidoneActive comparatorAfter a run-in period of 2-3 weeks on Chlorthalidone, patients will be randomized to the addition of KMgCit for 4 months.
Receives: Drug: Potassium Magnesium Citrate (KMgCit); Drug: Chlorthalidone
KCl + ChlorthalidoneActive comparatorAfter a run-in period of 2-3 weeks on Chlorthalidone, patients will be randomized to the addition of KCl for 4 months.
Receives: Drug: Potassium Chloride (KCl); Drug: Chlorthalidone

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: week 4 and week 16

Secondary outcomes (3)

  1. Chang in Hepatic Fat Measured at Baseline and Week 16

    Will be measured using hepatic magnetic resonance imaging at baseline and at week 16

    Measured: baseline to week 16

  2. Change in Muscle Magnesium Content Measured at Baseline and Week 16

    Will be measured using magnetic resonance imaging at baseline and at week 16

    Measured: baseline to week 16

  3. Change in FGF23 From Week 4 to Week 16

    Will be measured from venous blood sample from week 4 to week 16

    Measured: week 4 to week 16

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2016 (estimated)
  2. Study startJan 2015
  3. Primary completion4 Nov 2022
  4. Study completion4 Nov 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
61 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02665117
Sponsor's protocol ID
STU 092015-058
Status last verified
Oct 2023
First submitted
22 Jan 2016
Last updated
25 Oct 2023
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 22939974

  • Carter 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.

    PubMed 18504319

  • Guerrero-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.

    PubMed 16598698

  • Hata 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.

    PubMed 23758216

  • Koenig 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.

    PubMed 1988724

  • Odvina 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.

    PubMed 16645424

  • Pak CY. Correction of thiazide-induced hypomagnesemia by potassium-magnesium citrate from review of prior trials. Clin Nephrol. 2000 Oct;54(4):271-5.

    PubMed 11076102

  • Price 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.

    PubMed 23837919

  • Ruml 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.

    PubMed 10401023

  • Vongpatanasin 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.

    PubMed 37846572

Questions about this trial

What is this clinical trial studying?

A study testing Potassium Magnesium Citrate (KMgCit), Potassium Chloride (KCl) and Chlorthalidone in people with Hypertension, run by University of Texas Southwestern Medical Center at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Fasting Plasma Glucose From Week 4 to Week 16 (time frame: week 4 and week 16). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02665117, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Oct 2023.

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