EffCaMgCit to Prevent Mineral Metabolism and Renal Complications of Chronic PPI Therapy

Osteoporosis Clinical Trial

Official title:

Effervescent Calcium Magnesium Citrate to Prevent Mineral Metabolism and Renal Complications of Chronic Proton Pump Inhibitor Therapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05998863
• Other study ID #: STU-2023-0340
• Status: Recruiting
• Phase: Phase 3
• Start date: April 19, 2024
• Est. completion date: December 31, 2025

Study information

• Verified date: May 2024
• Source: University of Texas Southwestern Medical Center
• Contact: Khashayar Sakhaee, MD
• Phone: 214-648-0324
• Email: Khashayar.Sakhaee[@]UTSouthwestern.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 56
• Est. completion date: December 31, 2025
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hypomagnesemia
• Osteoporosis

Intervention

Drug:
• EffCaMgCit
Each sachet of EffCaMgCit will contain 19 meq or 380 mg calcium, 10 meq (122 mg) magnesium, and 50 meq total citrate.

Other:
• Placebo
Each sachet of Placebo will contain microcrystalline cellulose, but no calcium, magnesium or citrate.

Locations

Country	Name	City	State
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	UT Southwestern Medical Center	Dallas	Texas

Sponsors (1)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Bone Mineral Density (BMD) T-Score at 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.	Baseline and 1 year
Primary	Change From Baseline in the Fractional Excretion of Magnesium (FEMg) at 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.	Baseline and 1 year
Primary	Change from baseline in endogenous creatinine clearance at 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)).	Baseline and 1 year
Primary	Change From Baseline in Bone Mineral Density (BMD) Z-Score at 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.	Baseline and 1 year
Primary	Change From Baseline in Free Muscle Magnesium at 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).	Baseline and 1 year
Secondary	Change in Serum Parathyroid Function (PTH)	Change from baseline in serum parathyroid function (PTH) at 1 year will be measured by Biomerica Intact-PTH ELISA.	Baseline and 1 year
Secondary	Change in C-terminal telopeptide (CTX)	Change from baseline in serum bone resorption marker C-terminal telopeptide (CTX) at 1 year will be measured by lab finding utilizing ELISA CTX-I (CrossLaps).	Baseline and 1 year
Secondary	Change in Serum Magnesium	Change from baseline in serum magnesium at 1 year will be measured by ion selective electrode.	Baseline and 1 year
Secondary	Change in Urine Magnesium	Change from baseline in urine magnesium at 1 year measured by atomic absorption.	Baseline and 1 year