OsteoporosisPhase 3NCT03812380

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

A Phase 3 study testing EffCaMgCit in people with Osteoporosis and Hypomagnesemia, run by University of Texas Southwestern Medical Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 21 to 99 yearsHealthy volunteers can take part
Conditions the study is for: Osteoporosis, Hypomagnesemia
What is being tested?: EffCaMgCit
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 62 participants
Where: 1 siteUnited States
Study dates: 1 Jan 2019to 11 Aug 2021
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 21 to 99 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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%

Who cannot join

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Texas Southwestern Medical Center
Dallas, Texas, 75390

Other trials in United States

About this study

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).

Read the 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.

Conditions: Osteoporosis, Hypomagnesemia
Being tested: EffCaMgCit, Placebo
Keywords: Bone mineral density
Medical subject headings: Osteoporosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT03812380
Study group	Role	What they receive
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. Receives: 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. Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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))
Measured: Baseline and 2 years

Secondary outcomes (5)

Change From Baseline in Serum Parathyroid Function (PTH) at 2 Years
Change from baseline in serum parathyroid function (PTH) at 2 years will be measured by Biomerica Intact-PTH ELISA.
Measured: Baseline and 2 years
Change From Baseline in Serum Bone Resorption Marker C-terminal Telopeptide (CTX) at 2 Years
Change from baseline in serum bone resorption marker C-terminal telopeptide (CTX) at 2 years will be measured by lab finding utilizing ELISA CTX-I (CrossLaps).
Measured: Baseline and 2 years
Change From Baseline in Serum Magnesium at 2 Years
Change from baseline in serum magnesium at 2 years will be measured by ion selective electrode.
Measured: Baseline and 2 years
Change From Baseline in Urine Magnesium at 2 Years
Change from baseline in urine magnesium at 2 years was measured by by atomic absorption.
Measured: Baseline and 2 years
Change From Baseline in Serum Bicarbonate at 2 Years
Change from baseline in serum bicarbonate at 2 years will be measured to see improvement in acid based status in lowering kidney function impairment.
Measured: Baseline and 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Jan 201911 Aug 2021

First posted23 Jan 2019
Study start1 Jan 2019
Primary completion11 Aug 2021
Study completion11 Aug 2021

Why it stopped: The study was terminated due to a severe decrease in enrollment over the years 2020 and 2021. The major obstacle which hindered participation of subjects was the COVID-19 pandemic. Research was halted. Remaining study patients were withdrawn.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for OsteoporosisStudies of the same condition, open and under way.
More trials run by University of Texas Southwestern Medical CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 62 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03812380
Sponsor's protocol ID: STU 042018-078
Status last verified: Jul 2022
First submitted: 24 May 2018
Last updated: 17 Aug 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 17 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Averting Complications of Proton Pump Inhibitor Therapy by Effervescent Calcium Magnesium Citrate
ClinicalTrials.gov ID: NCT03812380
Acronym / sponsor ID: STU 042018-078
Conditions: Osteoporosis, Hypomagnesemia
Keywords: Bone mineral density
Phase: Phase 3
Study type: Interventional
Recruitment status: TerminatedReason stopped: The study was terminated due to a severe decrease in enrollment over the years 2020 and 2021. The major obstacle which hindered participation of subjects was the COVID-19 pandemic. Research was halted. Remaining study patients were withdrawn.
Enrolment: 62 participants (actual)
Lead sponsor: University of Texas Southwestern Medical CenterUniversity, hospital or other
Study start: 1 Jan 2019 (actual)
Primary completion: 11 Aug 2021 (actual)
Study completion: 11 Aug 2021 (actual)
First posted: 23 Jan 2019 (actual)
Results: Posted 17 Aug 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
EffCaMgCit	Experimental	Drug: EffCaMgCit19 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.
Placebo	Placebo comparator	Other: PlaceboEach 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.

Who may qualify

Ages: 21 to 99 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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%

Key exclusion criteria (8 listed)

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%

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
EffCaMgCitAlso: Effervescent calcium magnesium citrateEach sachet of EffCaMgCit will contain 19 meq or 380 mg calcium, 10 meq (122 mg) magnesium, and 50 meq total citrate.	Drug	EffCaMgCit
PlaceboEach 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

Primary outcome

Change From Baseline in Bone Mineral Density (BMD) T-Score at 2 Years
Time frame: Baseline and 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.
Change From Baseline in Bone Mineral Density (BMD) Z-Score at 2 Years
Time frame: Baseline and 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.
Change From Baseline in the Fractional Excretion of Magnesium (FEMg) at 2 Years
Time frame: Baseline and 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.
Change From Baseline in Free Muscle Magnesium at 2 Years
Time frame: Baseline and 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).
Change From Baseline in Endogenous Creatinine Clearance at 2 Years
Time frame: Baseline and 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))

5 secondary outcomes

Change From Baseline in Serum Parathyroid Function (PTH) at 2 Years
Time frame: Baseline and 2 years
Change From Baseline in Serum Bone Resorption Marker C-terminal Telopeptide (CTX) at 2 Years
Time frame: Baseline and 2 years
Change From Baseline in Serum Magnesium at 2 Years
Time frame: Baseline and 2 years
Change From Baseline in Urine Magnesium at 2 Years
Time frame: Baseline and 2 years
Change From Baseline in Serum Bicarbonate at 2 Years
Time frame: Baseline and 2 years

Results and safety

Results posted to the registry on 17 Aug 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
EffCaMgCit	22	0
Placebo	22	1

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

Time frame: Baseline and 2 years. Number. Unit: T-Score

Measure	EffCaMgCit n = 0	Placebo n = 1
L2-L4 T-Score	–	-0.4
Femoral Neck T-Score	–	-1.0
Total Hip T-Score	–	-0.7
Radial 1/3rd T-Score	–	-0.3

Population analysed: Because of severe enrollment difficulty due to COVID-19 restrictions and consequently a suspension of research activities, this study was terminated early. Only one subject completed the full two year duration for which data are summarized here.

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

Time frame: Baseline and 2 years. Number. Unit: Z-Score

Measure	EffCaMgCit n = 0	Placebo n = 1
L2L4 Z-Score	–	-0.1
Femoral Neck Z-Score	–	-0.8
Total Hip Z-Score	–	-0.7
Radial 1/3rd Z-Score	–	-0.1

Primary outcome: Change From Baseline in the Fractional Excretion of Magnesium (FEMg) at 2 Years

Time frame: Baseline and 2 years. Number. Unit: percentage

Measure	EffCaMgCit n = 0	Placebo n = 1
Value	–	-1.0

Primary outcome: Change From Baseline in Free Muscle Magnesium at 2 Years

Time frame: Baseline and 2 years. Number. Unit: mmol/L

Measure	EffCaMgCit n = 0	Placebo n = 1
Value	–	-0.044

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: From the participant's first dose at baseline (0 month) to the end of 24 months. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
EffCaMgCit	0 of 22 (0%)	1 of 22 (4.5%)	0 of 22
Placebo	0 of 22 (0%)	0 of 22 (0%)	0 of 22

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Khashayar Sakhaee, MD principal investigator

UTSW

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing EffCaMgCit in people with Osteoporosis and Hypomagnesemia, run by University of Texas Southwestern Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 17 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Aug 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Bone Mineral Density (BMD) T-Score at 2 Years (time frame: Baseline and 2 years). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03812380.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2022.