Prevalence and Intervention of Hypomagnesemia in Users of Proton-pump Inhibitors (Privet)

August 5, 2015 updated by: Joost Drenth, Radboud University Medical Center

Inulin- a Potential Preventive Dietary Supplement Against PPI Induced Hypomagnesemia

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

21

Phase

  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Chronic PPI use
  • Hypomagnesemia

Exclusion Criteria:

  • Uncontrolled diabetes
  • Irregular use of the inulin fibers

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Inulin
Intervention by inulin, max 20gr per day
Dietary supplement: Inulin
This is the Intervention
Other Names:
  • Beneo Orafti Synergy1
No Intervention: No Inulin
Same Patients of arm inulin. Here the phase without inulin supplementation (own controls)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cases and controls: Mean serum Mg2+ treatment effect of inulin (composite measure)
Time Frame: 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.
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)
Time Frame: 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.
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
Time Frame: 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.
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
Time Frame: 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.
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
Time Frame: 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.
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
Time Frame: 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.
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)
Time Frame: at day 0
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
Time Frame: DNA was extracted from blood, amplified and sequenced in average 2 months after bloodwithdrawal
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Radboud University Medical Center

Investigators

  • Principal Investigator: René Bindels, Professor, Radboud University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2014

Primary Completion (Actual)

February 1, 2015

Study Completion (Actual)

June 1, 2015

Study Registration Dates

First Submitted

June 26, 2015

First Submitted That Met QC Criteria

August 5, 2015

First Posted (Estimate)

August 10, 2015

Study Record Updates

Last Update Posted (Estimate)

August 10, 2015

Last Update Submitted That Met QC Criteria

August 5, 2015

Last Verified

August 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NL nr.: 47262.091.13
  • NL37289.091.11 (Other Identifier: 2011/272)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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