Preventing Metabolic Side Effects of Thiazide Diuretics With KMgCitrate
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 61
- 试验地点
- 3
- 主要终点
- Change in Fasting Plasma Glucose From Week 4 to Week 16
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Treated or untreated stage I hypertension
排除标准
- •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,
- •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
研究组 & 干预措施
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.
干预措施: Potassium Magnesium Citrate (KMgCit) (Drug)
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.
干预措施: Chlorthalidone (Drug)
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.
干预措施: Potassium Chloride (KCl) (Drug)
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.
干预措施: Chlorthalidone (Drug)
结局指标
主要结局
Change in Fasting Plasma Glucose From Week 4 to Week 16
时间窗: week 4 and week 16
Fasting plasma glucose was measured from venous blood sample at week 4 and week 16
次要结局
- Change in FGF23 From Week 4 to Week 16(week 4 to week 16)
- Change in Muscle Magnesium Content Measured at Baseline and Week 16(baseline to week 16)
- Chang in Hepatic Fat Measured at Baseline and Week 16(baseline to week 16)
研究者
Wanpen Vongpatanasin
Professor
University of Texas Southwestern Medical Center