Hypomagnesemia, Intestinal, With Secondary HypocalcemiaPrivetNCT02518659
Prevalence and Intervention of Hypomagnesemia in Users of Proton-pump Inhibitors
A study testing Inulin in people with Hypomagnesemia, Intestinal, With Secondary Hypocalcemia and Drug Induced Hypomagnesemia, run by Radboud University Medical Center.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Hypomagnesemia, Intestinal, With Secondary Hypocalcemia, Drug Induced Hypomagnesemia
- What is being tested?
- Inulin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- No sites listed yet
- Study dates
- Feb 2014to Jun 2015
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Chronic PPI use
- Hypomagnesemia
Who cannot join
- Uncontrolled diabetes
- Irregular use of the inulin fibers
About this study
Official title: 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.
Read the 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.
- Being tested
- Inulin
- Keywords
- hypomagnesemia, hypocalcemia, inulin, FOS, PPI, proton-pump inhibitors
- Medical subject headings
- Hypomagnesemia 1, Intestinal, Hypocalcemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
InulinDietary supplement
Also called Beneo Orafti Synergy1
This is the Intervention
| Study group | Role | What they receive |
|---|---|---|
| Inulin | Other | Intervention by inulin, max 20gr per day Receives: Dietary Supplement: Inulin |
| No Inulin | No intervention | Same Patients of arm inulin. Here the phase without inulin supplementation (own controls) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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 (7)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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)
Measured: DNA was extracted from blood, amplified and sequenced in average 2 months after bloodwithdrawal
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2015 (estimated)
- Study startFeb 2014
- Primary completionFeb 2015
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Hypomagnesemia, Intestinal, With Secondary HypocalcemiaStudies of the same condition, open and under way.
- More trials run by Radboud University 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 N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Joost Drenth, Radboud University Medical Center
- Investigators
- René Bindels, Professor, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02518659
- Sponsor's protocol ID
- NL nr.: 47262.091.13
- Other IDs
- NL37289.091.11
- Acronym
- Privet
- Status last verified
- Aug 2015
- First submitted
- 26 Jun 2015
- Last updated
- 10 Aug 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 22762246Lameris 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.
PubMed 23756852Coudray 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.
PubMed 12514257
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inulin- a Potential Preventive Dietary Supplement Against PPI Induced Hypomagnesemia
- ClinicalTrials.gov ID
- NCT02518659
- Acronym / sponsor ID
- Privet / NL nr.: 47262.091.13
- Keywords
- hypomagnesemia, hypocalcemia, inulin, FOS, PPI, proton-pump inhibitors
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- Feb 2014
- Primary completion
- Feb 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 10 Aug 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Inulin | Other | Dietary Supplement: InulinIntervention by inulin, max 20gr per day |
| No Inulin | No intervention | –Same Patients of arm inulin. Here the phase without inulin supplementation (own controls) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Chronic PPI use
- Hypomagnesemia
Key exclusion criteria (2 listed)
- Uncontrolled diabetes
- Irregular use of the inulin fibers
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 |
|---|---|---|
| InulinAlso: Beneo Orafti Synergy1This is the Intervention | Dietary supplement | Inulin |
Primary outcome
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.
7 secondary outcomes
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.
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.
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.
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.
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.
Cases and controls: General demographics of PPI users (Composite measure)
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2015.
- Background: PubMed 22762246Hess 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.
- Background: PubMed 23756852Lameris 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.
- Background: PubMed 12514257Coudray 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.
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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.
René Bindels, Professor principal investigator
Radboud University Medical Center
Questions about this trial
What is this clinical trial studying?
A study testing Inulin in people with Hypomagnesemia, Intestinal, With Secondary Hypocalcemia and Drug Induced Hypomagnesemia, run by Radboud University Medical Center.
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 2 inclusion and 2 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: finished, as of the sponsor's last update on 10 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
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.). 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 NCT02518659, which also lists 3 linked publications.
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 10 Aug 2015.