Clinical trial NCT05998863: EffCaMgCit to Prevent Mineral Metabolism and Renal Complications of Chronic PPI Therapy
Official title: Effervescent Calcium Magnesium Citrate to Prevent Mineral Metabolism and Renal Complications of Chronic Proton Pump Inhibitor Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Osteoporosis
Hypomagnesemia
Keywords: Bone mineral density
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2023-08-21
Enrollment: 56
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: TREATMENT

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 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.

Eligibility criteria: Inclusion Criteria:

* 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%

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
* Required to take calcium

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 1 Year
timeFrame: Baseline and 1 year
measure: Change From Baseline in the Fractional Excretion of Magnesium (FEMg) at 1 Year
timeFrame: Baseline and 1 year
measure: Change from baseline in endogenous creatinine clearance at 1 year.
timeFrame: Baseline and 1 year
measure: Change From Baseline in Bone Mineral Density (BMD) Z-Score at 1 Year
timeFrame: Baseline and 1 year
measure: Change From Baseline in Free Muscle Magnesium at 1 Year
timeFrame: Baseline and 1 year
Secondary outcomes:
measure: Change in Serum Parathyroid Function (PTH)
timeFrame: Baseline and 1 year
measure: Change in C-terminal telopeptide (CTX)
timeFrame: Baseline and 1 year
measure: Change in Serum Magnesium
timeFrame: Baseline and 1 year
measure: Change in Urine Magnesium
timeFrame: Baseline and 1 year
Other outcomes:
Locations:
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
Study officials:
affiliation: UTSW
name: Khashayar Sakhaee, MD
role: PRINCIPAL_INVESTIGATOR
References: