Prevalence and Intervention of Hypomagnesemia in Users of Proton-pump Inhibitors

Study Overview
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Brief Summary
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Hypomagnesemia is a severe side effect of longterm use of all available proton-pump inhibitors (PPIH). It develops due to intestinal malabsorption of Mg2+. This study investigates the application of dietary inulin fibers in users of proton-pump inhibitors with such a hypomagnesemia. To this end, repetitive short-term trials of 14 days of orally administered inulin, separated by a wash-out period of 14 days each were performed in cases of PPIH and controls. This study was not blinded or randomized.

Detailed Description
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Hypomagnesemia due to PPI use (PPIH) has a low frequency, but is a difficult to control side effect in clinical practice. It develops over years and results in severe symptoms related to the hypomagnesemia. Due to the widespread use of PPIs, the real number of PPIH may be high. Currently, there is a lack of intervention strategies and no general treatment protocols for patients exist. It is generally anticipated that PPI-withdrawal and antacid replacement therapy is the only working method to recover patients from the hypomagnesemia. However, this frequently resulted in rebound of gastric acid related complaints. The molecular mechanism of PPIH involves a reduction of Mg2+ absorption by the large intestine. Inulin fibers have been shown to have prebiotic properties. The intestinal microbiome ferments inulin and releases butyrate into the luminal compartment of the intestine. This results in acidification which enhances the uptake of Mg2+ and Ca2+ mediated by pH-sensitive ionchannels.Thus inulin may counteract PPI induced reduction of luminal protons and therefore reestablish normal Mg2+ absorption. To this end cases with PPIH and controls underwent two 14 day trials of orally administered inulin under separated by wash-out periods of 14 days. During the experimental phase blood measures of electrolytes were monitored.

Official Title
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Inulin- a Potential Preventive Dietary Supplement Against PPI Induced Hypomagnesemia

Conditions
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Drug Induced Hypomagnesemia, Hypomagnesemia, Intestinal, With Secondary Hypocalcemia

Intervention / Treatment
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* Dietary Supplement: Inulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic PPI use Hypomagnesemia Exclusion Criteria: Uncontrolled diabetes Irregular use of the inulin fibers

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Inulin<br>Intervention by inulin, max 20gr per day | Dietary Supplement: Inulin<br>* This is the Intervention<br>* Other names: Beneo Orafti Synergy1;|
| No Intervention: No Inulin<br>Same Patients of arm inulin. Here the phase without inulin supplementation (own controls) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cases and controls: Mean serum Mg2+ treatment effect of inulin (composite measure) | Measured values at respective timepoints are denoted as means +/- SEM in mmol/L. The treatment effect is calculated by the overall mean change of serum Mg2+ during the two inulin treated phases (Days 0 - 14 and days 28 - 42) and expressed as mean +/- SEM. | Cases and controls were followed for 56 days. Single measures of serum Mg2+ (in mmol/L) were performed at days 0, 14, 28,42 and 56. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cases and controls: Mean serum Ca2+ treatment effect of inulin (composite measure) | Measured values at respective timepoints are denoted as means +/- SEM in mmol/L. The treatment effect is calculated by the overall mean change of serum Ca2+ during the two inulin treated phases (Days 0 - 14 and days 28 - 42) and expressed as mean +/- SEM. | Cases and controls were followed for 56 days. Single measures of serum Ca2+ (in mmol/L) were performed at days 0, 14, 28,42 and 56. | 
| Cases only: 24-hrs urine Mg2+ excretion without inulin at days 27/28 | Measured values for respective timepoint is denoted as a mean +/- SEM in mmol/24hrs. | Collected 24-hrs urine samples are taken from each case at days 27/28. Samples were stored and measured within one week after day 56, the finalizing day of the respective participant. | 
| Cases only: 24-hrs urine Mg2+ excretion with inulin at days 41/42 | Measured values for respective timepoint is denoted as a mean +/- SEM in mmol/24hrs. | Collected 24-hrs urine samples are taken from each case at days 41/42. Samples were stored and measured within one week after day 56, the finalizing day of the respective participant. | 
| Cases only: 24-hrs urine Ca2+ excretion without inulin at days 27/28 | Measured values for respective timepoint is denoted as a mean +/- SEM in mmol/24hrs. | Collected 24-hrs urine samples are taken from each case at days 27/28. Samples were stored and measured within one week after day 56, the finalizing day of the respective participant. | 
| Cases only: 24-hrs urine Ca2+ excretion with Inulin at days 41/42 | Measured values for respective timepoint is denoted as a mean +/- SEM in mmol/24hrs. | Collected 24-hrs urine samples are taken from each case at days 41/42. Samples were stored and measured within one week after day 56, the finalizing day of the respective participant. | 
| Cases and controls: General demographics of PPI users (Composite measure) | Demographical data, extracted from patient reports with relevant data such as age, sex, PPI-use and Duration and relevant comorbidities | at day 0 | 
| Cases and Controls: Genetic screen of polymorphisms in the TRPM6 gene | Small PCR and Sanger sequencing of exons 26+27 of the gene TRPM6 (Mg2+ channel) | DNA was extracted from blood, amplified and sequenced in average 2 months after bloodwithdrawal | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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inulin, hypomagnesemia, hypocalcemia, PPI, proton-pump inhibitors, FOS