Clinical trial NCT02518659: Prevalence and Intervention of Hypomagnesemia in Users of Proton-pump Inhibitors
Official title: Inulin- a Potential Preventive Dietary Supplement Against PPI Induced Hypomagnesemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypomagnesemia, Intestinal, With Secondary Hypocalcemia
Drug Induced Hypomagnesemia
Keywords: hypomagnesemia
hypocalcemia
inulin
FOS
PPI
proton-pump inhibitors
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2015-08-10
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

* Chronic PPI use
* Hypomagnesemia

Exclusion Criteria:

* Uncontrolled diabetes
* Irregular use of the inulin fibers

Primary outcomes:
measure: Cases and controls: Mean serum Mg2+ treatment effect of inulin (composite measure)
timeFrame: 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 outcomes:
measure: Cases and controls: Mean serum Ca2+ treatment effect of inulin (composite measure)
timeFrame: 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.
measure: Cases only: 24-hrs urine Mg2+ excretion without inulin at days 27/28
timeFrame: 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.
measure: Cases only: 24-hrs urine Mg2+ excretion with inulin at days 41/42
timeFrame: 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.
measure: Cases only: 24-hrs urine Ca2+ excretion without inulin at days 27/28
timeFrame: 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.
measure: Cases only: 24-hrs urine Ca2+ excretion with Inulin at days 41/42
timeFrame: 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.
measure: Cases and controls: General demographics of PPI users (Composite measure)
timeFrame: at day 0
measure: Cases and Controls: Genetic screen of polymorphisms in the TRPM6 gene
timeFrame: DNA was extracted from blood, amplified and sequenced in average 2 months after bloodwithdrawal
Other outcomes:
Locations:
Study officials:
affiliation: Radboud University Medical Center
name: René Bindels, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hess MW, Hoenderop JG, Bindels RJ, Drenth JP. Systematic review: hypomagnesaemia induced by proton pump inhibition. Aliment Pharmacol Ther. 2012 Sep;36(5):405-13. doi: 10.1111/j.1365-2036.2012.05201.x. Epub 2012 Jul 4.
citation: Lameris AL, Hess MW, van Kruijsbergen I, Hoenderop JG, Bindels RJ. Omeprazole enhances the colonic expression of the Mg(2+) transporter TRPM6. Pflugers Arch. 2013 Nov;465(11):1613-20. doi: 10.1007/s00424-013-1306-0. Epub 2013 Jun 12.
citation: Coudray C, Demigne C, Rayssiguier Y. Effects of dietary fibers on magnesium absorption in animals and humans. J Nutr. 2003 Jan;133(1):1-4. doi: 10.1093/jn/133.1.1.