Effervescent Calcium Magnesium Citrate to Prevent Mineral Metabolism and Renal Complications of Chronic Proton Pump Inhibitor Therapy
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 入组人数
- 56
- 试验地点
- 3
- 主要终点
- Change From Baseline in Bone Mineral Density (BMD) T-Score at 1 Year
研究概览
简要总结
Proton pump inhibitors (PPIs) are widely used for the control of gastric ulcer-gastritis, erosive esophagitis (gastroesophageal reflux disease), peptic ulcer disease (duodenal ulcer), and heartburn. Despite their efficacy, their use has been implicated in possibly causing fragility fractures (osteoporosis), hypomagnesemia (magnesium deficiency) and increased risk of chronic kidney disease (CKD). The current trial represents the investigators ongoing effort to discern whether these complications could be averted by effervescent calcium magnesium citrate (EffCaMgCit).
详细描述
In the current proposal, the investigators wish to conduct a 1-year treatment trial, directed at obtaining more definitive evidence that EffCaMgCit overcomes all three complications of PPI.
Aim 1. To test the hypothesis that EffCaMgCit would prevent/treat osteoporosis, by suppressing parathyroid function and bone resorption, thereby stabilizing bone mineral density (BMD). The critical endpoint will be overall change in BMD T-Score and Z-Score from baseline to the end of study. Secondary endpoints will be the change in serum PTH and C-terminal telopeptide (CTX).
Aim 2. To test the hypothesis that EffCaMgCit would prevent/treat hypomagnesemia/magnesium deficiency, by providing bioavailable magnesium. The critical endpoint will be the overall change in the fractional excretion of magnesium (FEMg) and free muscle magnesium by MRS from baseline to the end of study. Secondary endpoints will be the change in serum and urinary magnesium.
Aim 3. To test the hypothesis that EffCaMgCit would reduce the risk of CKD during PPI use by averting putative hypomagnesemia/magnesium deficiency and neutralizing acid load. The investigators propose that PPI causes hypomagnesemia/magnesium deficiency and confers an acid load, - factors implicated for incident CKD and its progression. EffCaMgCit is expected to avert incident CKD by providing bioavailable magnesium and alkali load. Critical endpoints will be the overall change in endogenous creatinine clearance, urinary alpha-1 microglobulin, and a measure of acid-base status.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
To provide adequate blinding, each medication sachet will be labelled with the study name, IRB number, principal investigator's name, expiration date and identification number of the study subject. Labels will be applied to the appropriate medication sachets once the subject has been randomized and assigned to a treatment group. Labelling of the sachets will be done by personnel who are not engaged in patient care.
入排标准
- 年龄范围
- 21 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Ambulatory adult subjects (> 21 years of age) of either gender of any ethnicity
- •Must have taken PPI (omeprazole or equivalent ≥ 20 mg/day, ≥ three times per week, for at least 2 months)
- •Expected to continue at a similar dosage
- •Stage 1 hypertension (with systolic blood pressure <140 and diastolic <90)
- •Controlled diabetes mellitus Type II with HbA1C less than 7%
排除标准
- •End-stage renal failure on dialysis
- •Hypercalcemia,
- •Hypophosphatemia (serum P < 2.5 mg/dL)
- •Hypertension stage 2 or higher
- •Diabetes Type II with HbA1C ≥ 7%
- •Treatment with adrenocorticosteroids, diuretics, non-steroidal anti-inflammatory agents - - Regular dose of magnesium supplements, bisphosphonate, teriparatide, denosumab or selective estrogen receptor modulators
- •Required to take calcium
- •Inclusion/exclusion of other drugs or conditions will be considered on an individual basis.
研究组 & 干预措施
EffCaMgCit
38 meq (760 mg) Ca, 20 meq (243 mg) Mg, and 100 meq total citrate per day; designed to be added to 6 oz water for 1-2 minutes, to be dissolved/suspended before swallowing.
干预措施: EffCaMgCit (Drug)
Placebo
Each sachet of Placebo will contain microcrystalline cellulose, but no calcium, magnesium or citrate. Placebo will be added to 6 oz water for 1-2 minutes, to be dissolved/suspended before swallowing.
干预措施: Placebo (Other)
结局指标
主要结局
Change From Baseline in Bone Mineral Density (BMD) T-Score at 1 Year
时间窗: Baseline and 1 year
Change in Bone Mineral Density (BMD) T-Score from baseline to 1 Year as measured by dual photon absorptiometry. The range, as defined by the World Health Organization (WHO), for T-Score is: -1 and above = Normal, Between -1 and -2.5 = Osteopenia, -2.5 and below = osteoporosis.
Change From Baseline in the Fractional Excretion of Magnesium (FEMg) at 1 Year
时间窗: Baseline and 1 year
Change From Baseline in the Fractional Excretion of Magnesium (FEMg) at 1 Year as measured by the ratio of magnesium clearance and creatinine clearance, using 24-h urinary magnesium and creatinine and corresponding serum magnesium and creatinine obtained post meal/load.
Change from baseline in endogenous creatinine clearance at 1 year.
时间窗: Baseline and 1 year
Change from baseline in endogenous creatinine clearance at 1 year. Endogenous creatinine clearance will be obtained by using 24-h urinary creatinine and post-meal/load venous blood sample ((uCr, mg/24hr) / (sCr, mg/dL \* 14.4)) as well as using the Cockcroft and Gault formula (\[(140 - age) x TBW\] / (Scr x 72) (x 0.85 for females)).
Change From Baseline in Bone Mineral Density (BMD) Z-Score at 1 Year
时间窗: Baseline and 1 year
Change From Baseline in Bone Mineral Density (BMD) Z-Score at 1 Year as measured by dual photon absorptiometry. Outcome is considered positive if the Z Score after one year of treatment becomes less negative (less than -2). There is no specific score range for the Z Score.
Change From Baseline in Free Muscle Magnesium at 1 Year
时间窗: Baseline and 1 year
Change From baseline in free muscle magnesium at 1 year as assessed by measuring intracellular Mg in a calf muscle, by using 31P (Phosphorous) magnetic resonance spectroscopy (MRS).
次要结局
- Change in C-terminal telopeptide (CTX)(Baseline and 1 year)
- Change in Urine Magnesium(Baseline and 1 year)
- Change in Serum Parathyroid Function (PTH)(Baseline and 1 year)
- Change in Serum Magnesium(Baseline and 1 year)
研究者
Khashayar Sakhaee
Professor, Internal Medicine
University of Texas Southwestern Medical Center