Trial Outcomes & Findings for Averting Complications of Proton Pump Inhibitor Therapy by Effervescent Calcium Magnesium Citrate (NCT NCT03812380)

NCT ID: NCT03812380

Last Updated: 2022-08-17

Results Overview

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.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 62 participants
• Primary outcome timeframe: Baseline and 2 years
• Results posted on: 2022-08-17

Participant Flow

Out of the 62 participants enrolled, only 44 met the inclusion criteria and were randomized to the treatment.

Participant milestones

Measure	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. EffCaMgCit: Each sachet of EffCaMgCit will contain 19 meq or 380 mg calcium, 10 meq (122 mg) magnesium, and 50 meq total citrate.	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. 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.
Overall Study STARTED	22	22
Overall Study COMPLETED	0	1
Overall Study NOT COMPLETED	22	21

Reasons for withdrawal

Measure	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. EffCaMgCit: Each sachet of EffCaMgCit will contain 19 meq or 380 mg calcium, 10 meq (122 mg) magnesium, and 50 meq total citrate.	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. 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.
Overall Study Protocol Violation	3	3
Overall Study Withdrawal by Subject	5	4
Overall Study Early termination of study	14	14

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	EffCaMgCit n=22 Participants 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. EffCaMgCit: Each sachet of EffCaMgCit will contain 19 meq or 380 mg calcium, 10 meq (122 mg) magnesium, and 50 meq total citrate.	Placebo n=22 Participants 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: 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.	Total n=44 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	12 Participants n=5 Participants	16 Participants n=7 Participants	28 Participants n=5 Participants
Age, Categorical >=65 years	10 Participants n=5 Participants	6 Participants n=7 Participants	16 Participants n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	15 Participants n=7 Participants	27 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	7 Participants n=7 Participants	17 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	22 Participants n=5 Participants	21 Participants n=7 Participants	43 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	20 Participants n=5 Participants	21 Participants n=7 Participants	41 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	22 participants n=5 Participants	22 participants n=7 Participants	44 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 2 years

Population: 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.

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.

Outcome measures

Measure	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. EffCaMgCit: Each sachet of EffCaMgCit will contain 19 meq or 380 mg calcium, 10 meq (122 mg) magnesium, and 50 meq total citrate.	Placebo n=1 Participants 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: 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.
Change From Baseline in Bone Mineral Density (BMD) T-Score at 2 Years L2-L4 T-Score	—	-0.4 T-Score
Change From Baseline in Bone Mineral Density (BMD) T-Score at 2 Years Femoral Neck T-Score	—	-1.0 T-Score
Change From Baseline in Bone Mineral Density (BMD) T-Score at 2 Years Total Hip T-Score	—	-0.7 T-Score
Change From Baseline in Bone Mineral Density (BMD) T-Score at 2 Years Radial 1/3rd T-Score	—	-0.3 T-Score

PRIMARY outcome

Timeframe: Baseline and 2 years

Population: 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.

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.

Outcome measures

Measure	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. EffCaMgCit: Each sachet of EffCaMgCit will contain 19 meq or 380 mg calcium, 10 meq (122 mg) magnesium, and 50 meq total citrate.	Placebo n=1 Participants 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: 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.
Change From Baseline in Bone Mineral Density (BMD) Z-Score at 2 Years L2L4 Z-Score	—	-0.1 Z-Score
Change From Baseline in Bone Mineral Density (BMD) Z-Score at 2 Years Femoral Neck Z-Score	—	-0.8 Z-Score
Change From Baseline in Bone Mineral Density (BMD) Z-Score at 2 Years Total Hip Z-Score	—	-0.7 Z-Score
Change From Baseline in Bone Mineral Density (BMD) Z-Score at 2 Years Radial 1/3rd Z-Score	—	-0.1 Z-Score

PRIMARY outcome

Timeframe: Baseline and 2 years

Population: 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.

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.

Outcome measures

Measure	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. EffCaMgCit: Each sachet of EffCaMgCit will contain 19 meq or 380 mg calcium, 10 meq (122 mg) magnesium, and 50 meq total citrate.	Placebo n=1 Participants 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: 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.
Change From Baseline in the Fractional Excretion of Magnesium (FEMg) at 2 Years	—	-1.0 percentage

PRIMARY outcome

Timeframe: Baseline and 2 years

Population: 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.

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).

Outcome measures

Measure	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. EffCaMgCit: Each sachet of EffCaMgCit will contain 19 meq or 380 mg calcium, 10 meq (122 mg) magnesium, and 50 meq total citrate.	Placebo n=1 Participants 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: 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.
Change From Baseline in Free Muscle Magnesium at 2 Years	—	-0.044 mmol/L

PRIMARY outcome

Timeframe: Baseline and 2 years

Population: Because of severe decrease in enrolled participants due to COVID-19 restrictions and consequently a suspension of research activities resulted in the early termination of this study. Only 1 subject completed the 2 year timepoint for which the data is summarized here.

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))

Outcome measures

Measure	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. EffCaMgCit: Each sachet of EffCaMgCit will contain 19 meq or 380 mg calcium, 10 meq (122 mg) magnesium, and 50 meq total citrate.	Placebo n=1 Participants 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: 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.
Change From Baseline in Endogenous Creatinine Clearance at 2 Years	—	13 ml/min

SECONDARY outcome

Timeframe: Baseline and 2 years

Population: 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.

Change from baseline in serum parathyroid function (PTH) at 2 years will be measured by Biomerica Intact-PTH ELISA.

Outcome measures

Measure	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. EffCaMgCit: Each sachet of EffCaMgCit will contain 19 meq or 380 mg calcium, 10 meq (122 mg) magnesium, and 50 meq total citrate.	Placebo n=1 Participants 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: 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.
Change From Baseline in Serum Parathyroid Function (PTH) at 2 Years	—	75 pg/ml

SECONDARY outcome

Timeframe: Baseline and 2 years

Population: 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.

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).

Outcome measures

Measure	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. EffCaMgCit: Each sachet of EffCaMgCit will contain 19 meq or 380 mg calcium, 10 meq (122 mg) magnesium, and 50 meq total citrate.	Placebo n=1 Participants 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: 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.
Change From Baseline in Serum Bone Resorption Marker C-terminal Telopeptide (CTX) at 2 Years	—	0.15 ng/ml

SECONDARY outcome

Timeframe: Baseline and 2 years

Population: 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.

Change from baseline in serum magnesium at 2 years will be measured by ion selective electrode.

Outcome measures

Measure	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. EffCaMgCit: Each sachet of EffCaMgCit will contain 19 meq or 380 mg calcium, 10 meq (122 mg) magnesium, and 50 meq total citrate.	Placebo n=1 Participants 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: 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.
Change From Baseline in Serum Magnesium at 2 Years	—	0.2 mg/dL

SECONDARY outcome

Timeframe: Baseline and 2 years

Population: 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.

Change from baseline in urine magnesium at 2 years was measured by by atomic absorption.

Outcome measures

Measure	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. EffCaMgCit: Each sachet of EffCaMgCit will contain 19 meq or 380 mg calcium, 10 meq (122 mg) magnesium, and 50 meq total citrate.	Placebo n=1 Participants 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: 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.
Change From Baseline in Urine Magnesium at 2 Years	—	-8 mg/day

SECONDARY outcome

Timeframe: Baseline and 2 years

Population: 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.

Change from baseline in serum bicarbonate at 2 years will be measured to see improvement in acid based status in lowering kidney function impairment.

Outcome measures

Measure	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. EffCaMgCit: Each sachet of EffCaMgCit will contain 19 meq or 380 mg calcium, 10 meq (122 mg) magnesium, and 50 meq total citrate.	Placebo n=1 Participants 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: 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.
Change From Baseline in Serum Bicarbonate at 2 Years	—	-2 mmol/L

Adverse Events

EffCaMgCit

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	EffCaMgCit n=22 participants at risk 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. EffCaMgCit: Each sachet of EffCaMgCit will contain 19 meq or 380 mg calcium, 10 meq (122 mg) magnesium, and 50 meq total citrate.	Placebo n=22 participants at risk 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: 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.
General disorders Gas, smelly gas and bloating	4.5% 1/22 • From the participant's first dose at baseline (0 month) to the end of 24 months A severe decrease in the enrolled participants due to COVID restrictions and consequently a suspension of research activities resulted in the early termination of this study.	0.00% 0/22 • From the participant's first dose at baseline (0 month) to the end of 24 months A severe decrease in the enrolled participants due to COVID restrictions and consequently a suspension of research activities resulted in the early termination of this study.

Additional Information

Khashayar Sakhaee, MD

UT Southwestern Medical Center

Phone: 214-648-0324

Email: Khashayar.Sakhaee@UTSouthwestern.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place