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Averting Complications of Proton Pump Inhibitor Therapy by Effervescent Calcium Magnesium Citrate

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ClinicalTrials.gov Identifier: NCT03812380
Recruitment Status : Recruiting
First Posted : January 23, 2019
Last Update Posted : January 25, 2019
Sponsor:
Information provided by (Responsible Party):
Khashayar Sakhaee, University of Texas Southwestern Medical Center

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).

Condition or disease Intervention/treatment Phase
Osteoporosis Hypomagnesemia Drug: EffCaMgCit Other: Placebo Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes 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.
Primary Purpose: Prevention
Official Title: Averting Complications of Proton Pump Inhibitor Therapy by Effervescent Calcium Magnesium Citrate
Actual Study Start Date : January 1, 2019
Estimated Primary Completion Date : December 30, 2020
Estimated Study Completion Date : December 30, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Calcium Osteoporosis

Arm Intervention/treatment
Experimental: EffCaMgCit
19 meq or 380 mg calcium, 10 meq (122 mg) magnesium, and 50 meq total citrate; designed to be added to 6 oz water for 1-2 minutes, to be dissolved/suspended before swallowing. Each sachet of EffCaMgCit will contain 400 units of vitamin D.
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 Name: Effervescent calcium magnesium citrate

Placebo Comparator: 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. The placebo will contain 400 units of vitamin D.
Other: 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. The placebo will contain 400 units of vitamin D.




Primary Outcome Measures :
  1. Measure BMD using DXA scan to show effectiveness of EffCaMgCit [ Time Frame: 2 years ]
    To test the hypothesis that EffCaMgCit would prevent/treat osteoporosis, thereby stabilizing bone mineral density (BMD).

  2. Fractional Excretion of Magnesium (FEMg) [ Time Frame: 2 years ]
    To indirectly measure total magnesium content.

  3. Free muscle magnesium by MRS [ Time Frame: 2 years ]
    Direct measurement of tissue magnesium content.

  4. Endogenous creatinine clearance [ Time Frame: 2 years ]
    To measure the degree of renal functional status.


Secondary Outcome Measures :
  1. Measure serum PTH [ Time Frame: 2 years ]
    Suppressing parathyroid function to improve bone mineral density.

  2. Serum bone resorption marker C-terminal telopeptide (CTX) [ Time Frame: 2 years ]
    To determine the degree of the fall in serum PTH resulting in a decreased bone resorption.

  3. Serum magnesium [ Time Frame: 2 years ]
    Indirect measure of the degree of magnesium deficiency.

  4. Urine Magnesium [ Time Frame: 2 years ]
    Indirect measure of the degree of magnesium deficiency.

  5. Serum bicarbonate [ Time Frame: 2 years ]
    To measure improvement in acid based status in lowering kidney function impairment.



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Ages Eligible for Study:   21 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03812380


Contacts
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Contact: Khashayar Sakhaee, MD 214-648-0324 Khashayar.Sakhaee@UTSouthwestern.edu
Contact: Miranda King, MPH 214-648-2117 Miranda.King@utsouthwestern.edu

Locations
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United States, Texas
University of Texas Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Contact: Miranda King, MPH    214-648-2117    Miranda.King@utsouthwestern.edu   
Contact: Khashayar Sakhaee, MD    214-648-0324    Khashayar.Sakhaee@UTSouthwestern.edu   
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Investigators
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Principal Investigator: Khashayar Sakhaee, MD UTSW

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Responsible Party: Khashayar Sakhaee, Chief, Division of Mineral Metabolism; Professor, Internal Medicine, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT03812380     History of Changes
Other Study ID Numbers: 042018-078
First Posted: January 23, 2019    Key Record Dates
Last Update Posted: January 25, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Khashayar Sakhaee, University of Texas Southwestern Medical Center:
Bone mineral density

Additional relevant MeSH terms:
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Osteoporosis
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Metabolic Diseases
Vitamins
Vitamin D
Calcium, Dietary
Calcium
Citric Acid
Sodium Citrate
Proton Pump Inhibitors
Magnesium citrate
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents
Calcium-Regulating Hormones and Agents
Anticoagulants
Calcium Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Cathartics
Gastrointestinal Agents