Clinical trial NCT03812380: Averting Complications of Proton Pump Inhibitor Therapy by Effervescent Calcium Magnesium Citrate
Official title: Averting Complications of Proton Pump Inhibitor Therapy by Effervescent Calcium Magnesium Citrate
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Osteoporosis
Hypomagnesemia
Keywords: Bone mineral density
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2019-01-23
Enrollment: 62
Sex: ALL
Minimum age (years): 21
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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).

Detailed description: In a single-dose bioavailability study, the investigators showed previously that provision of calcium and magnesium in a soluble form as EffCaMgCit improved intestinal absorption of calcium and magnesium and suppressed parathyroid function during PPI treatment, compared with calcium carbonate. In a multidosing trial with esomeprazole 40 mg/day for 28 days, EffCaMgCit suppressed parathyroid function and bone turnover, and increased serum and urinary magnesium, compared with placebo. Moreover, EffCaMgCit co-administered with PPI conferred an alkali load, and averted apparent acid load conferred by PPI (when given with placebo).

In the current proposal, the investigators wish to conduct a 2-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 BMD. Secondary endpoints will be 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 fractional excretion of magnesium (FEMg) and free muscle magnesium by MRS. Secondary endpoints will be 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 endogenous creatinine clearance, FEMg, free muscle magnesium and acid-base status.

Eligibility criteria: Inclusion Criteria:

* 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%

Exclusion Criteria:

* 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.

Inclusion/exclusion of other drugs or conditions will be considered on an individual basis.

Primary outcomes:
measure: Change From Baseline in Bone Mineral Density (BMD) T-Score at 2 Years
timeFrame: Baseline and 2 years
measure: Change From Baseline in Bone Mineral Density (BMD) Z-Score at 2 Years
timeFrame: Baseline and 2 years
measure: Change From Baseline in the Fractional Excretion of Magnesium (FEMg) at 2 Years
timeFrame: Baseline and 2 years
measure: Change From Baseline in Free Muscle Magnesium at 2 Years
timeFrame: Baseline and 2 years
measure: Change From Baseline in Endogenous Creatinine Clearance at 2 Years
timeFrame: Baseline and 2 years
Secondary outcomes:
measure: Change From Baseline in Serum Parathyroid Function (PTH) at 2 Years
timeFrame: Baseline and 2 years
measure: Change From Baseline in Serum Bone Resorption Marker C-terminal Telopeptide (CTX) at 2 Years
timeFrame: Baseline and 2 years
measure: Change From Baseline in Serum Magnesium at 2 Years
timeFrame: Baseline and 2 years
measure: Change From Baseline in Urine Magnesium at 2 Years
timeFrame: Baseline and 2 years
measure: Change From Baseline in Serum Bicarbonate at 2 Years
timeFrame: Baseline and 2 years
Other outcomes:
Locations:
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
Study officials:
affiliation: UTSW
name: Khashayar Sakhaee, MD
role: PRINCIPAL_INVESTIGATOR
References: