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

Primary Purpose

Osteoporosis, Hypomagnesemia

Status
Not yet recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
EffCaMgCit
Placebo
Sponsored by
University of Texas Southwestern Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Osteoporosis focused on measuring Bone mineral density

Eligibility Criteria

21 Years - 99 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • University of Texas Southwestern Medical Center
  • UT Southwestern Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

EffCaMgCit

Placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.
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.
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)).
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.
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).

Secondary Outcome Measures

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.
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).
Change in Serum Magnesium
Change from baseline in serum magnesium at 1 year will be measured by ion selective electrode.
Change in Urine Magnesium
Change from baseline in urine magnesium at 1 year measured by atomic absorption.

Full Information

First Posted
August 3, 2023
Last Updated
August 10, 2023
Sponsor
University of Texas Southwestern Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT05998863
Brief Title
Effervescent Calcium Magnesium Citrate to Prevent Mineral Metabolism and Renal Complications of Chronic Proton Pump Inhibitor Therapy
Official Title
Effervescent Calcium Magnesium Citrate to Prevent Mineral Metabolism and Renal Complications of Chronic Proton Pump Inhibitor Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 1, 2023 (Anticipated)
Primary Completion Date
September 30, 2025 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Texas Southwestern Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoporosis, Hypomagnesemia
Keywords
Bone mineral density

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
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.
Allocation
Randomized
Enrollment
56 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
EffCaMgCit
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
EffCaMgCit
Other Intervention Name(s)
Effervescent calcium magnesium citrate
Intervention Description
Each sachet of EffCaMgCit will contain 19 meq or 380 mg calcium, 10 meq (122 mg) magnesium, and 50 meq total citrate.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Each sachet of Placebo will contain microcrystalline cellulose, but no calcium, magnesium or citrate.
Primary Outcome Measure Information:
Title
Change From Baseline in Bone Mineral Density (BMD) T-Score at 1 Year
Description
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.
Time Frame
Baseline and 1 year
Title
Change From Baseline in the Fractional Excretion of Magnesium (FEMg) at 1 Year
Description
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.
Time Frame
Baseline and 1 year
Title
Change from baseline in endogenous creatinine clearance at 1 year.
Description
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)).
Time Frame
Baseline and 1 year
Title
Change From Baseline in Bone Mineral Density (BMD) Z-Score at 1 Year
Description
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.
Time Frame
Baseline and 1 year
Title
Change From Baseline in Free Muscle Magnesium at 1 Year
Description
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).
Time Frame
Baseline and 1 year
Secondary Outcome Measure Information:
Title
Change in Serum Parathyroid Function (PTH)
Description
Change from baseline in serum parathyroid function (PTH) at 1 year will be measured by Biomerica Intact-PTH ELISA.
Time Frame
Baseline and 1 year
Title
Change in C-terminal telopeptide (CTX)
Description
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).
Time Frame
Baseline and 1 year
Title
Change in Serum Magnesium
Description
Change from baseline in serum magnesium at 1 year will be measured by ion selective electrode.
Time Frame
Baseline and 1 year
Title
Change in Urine Magnesium
Description
Change from baseline in urine magnesium at 1 year measured by atomic absorption.
Time Frame
Baseline and 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Khashayar Sakhaee, MD
Phone
214-648-0324
Email
Khashayar.Sakhaee@UTSouthwestern.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Miranda King, MPH
Phone
214-648-2117
Email
Miranda.King@utsouthwestern.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Khashayar Sakhaee, MD
Organizational Affiliation
UTSW
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390-9107
Country
United States
Facility Name
UT Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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

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