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

NCT03812380 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: STU 042018-078
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

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).

Conditions

Osteoporosis; Hypomagnesemia

Keywords

Bone mineral density

Outcome Measures

Primary Outcomes (5)

• Change From Baseline in Bone Mineral Density (BMD) T-Score at 2 Years

  Change from baseline in bone mineral density (BMD) T-Score at 2 years 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 2 years

• Change From Baseline in Bone Mineral Density (BMD) Z-Score at 2 Years

  Change from baseline in bone mineral density (BMD) Z-score at 2 years as measured by dual photon absorptiometry. Outcome is considered positive if the Z Score after two years of treatment becomes less negative (less than -2). There is no specific score range for the Z Score.

  Baseline and 2 years

• Change From Baseline in the Fractional Excretion of Magnesium (FEMg) at 2 Years

  Change from baseline in the fractional excretion of magnesium (FEMg) at 2 years 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 2 years

• Change From Baseline in Free Muscle Magnesium at 2 Years

  Change From baseline in free muscle magnesium at 2 years as assessed by measuring intracellular Mg in a calf muscle, by using 31P (Phosphorous) magnetic resonance spectroscopy (MRS).

  Baseline and 2 years

• Change From Baseline in Endogenous Creatinine Clearance at 2 Years

  Change from baseline in endogenous creatinine clearance at 2 years will be measured. 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))

  Baseline and 2 years

Secondary Outcomes (5)

• Change From Baseline in Serum Parathyroid Function (PTH) at 2 Years

  Baseline and 2 years

• Change From Baseline in Serum Bone Resorption Marker C-terminal Telopeptide (CTX) at 2 Years

  Baseline and 2 years

• Change From Baseline in Serum Magnesium at 2 Years

  Baseline and 2 years

• Change From Baseline in Urine Magnesium at 2 Years

  Baseline and 2 years

• Change From Baseline in Serum Bicarbonate at 2 Years

  Baseline and 2 years

Study Arms (2)

EffCaMgCit

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

EffCaMgCit DRUG

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

Also known as: Effervescent calcium magnesium citrate

EffCaMgCit

Placebo OTHER

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.

Placebo

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Osteoporosis

Interventions

effervescent calcium magnesium citrate

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Khashayar Sakhaee, MD
• Organization: UT Southwestern Medical Center

Khashayar.Sakhaee@UTSouthwestern.edu

214-648-0324

Study Officials

• Khashayar Sakhaee, MD

  UTSW

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief, Division of Mineral Metabolism; Professor, Internal Medicine

Study Record Dates

• First Submitted: May 24, 2018
• First Posted: January 23, 2019
• Study Start: January 1, 2019
• Primary Completion: August 11, 2021
• Study Completion: August 11, 2021
• Last Updated: August 17, 2022
• Results First Posted: August 17, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)