Objective: The primary objective is to determine if the dietary fructan-fiber inulin is applicable in PPIH. More specific, it aims to (i) improve the magnesium balance in cases of hypomagnesemic PPI users and (ii) to evaluate if the use of inulin is…
ID
Source
Brief title
Condition
- Malabsorption conditions
- Electrolyte and fluid balance conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main study parameters/endpoints: Main study parameter is serum Mg2+. PPI*s
exert their negative effect on serum Mg2+ in brisk manner and is influenced by
the overall Mg2+ status of the patient. Mg2+ depleted individuals react to
PPI-challenge within 4-5 days and gradually develop hypomagnesemia (serum Mg2+
< 0.7mmol/L). (6) Serum Mg2+ is measured twice in one two weeks (first trial
period at t=0d and t=14d, subsequently at t=28d, t=42d and t=56). t=0d gives
the start value and t=14d the end value (for the first trial period).
The primary endpoint is defined in two ways: First if the end value at t=14d is
20% reduced compared to start value at t=0d or, second, if the end value drops
to 0.55 mmol/L. The latter is important to prevent symptomatic hypomagnesemia
and to initiate appropriate supplementation (not expected). Vice versa,
hypomagnesemia (defined as serum Mg2+ > 1.1mmol) is second endpoint because it
can be indicative for renal failure or the use of antacids. (7)
Moreover, severe adverse reactions within trial periods irrespective of origin
will lead to immediate stop of intervention or alternative treatment.
Secondary outcome
na
Background summary
Rationale: Proton pump inhibitors (PPI*s) are used by millions of patients.
They are the mainstay of choice for several gastric acid related diseases like
GERD, peptic ulcers and H. Pylori eradication. PPIs have an excellent safety
profile, however, since 2006 case reports started to emerge that describe some
patients that develop symptomatic hypomagnesemia due to PPI use (Proton pump
inhibitor induced hypomagnesemia * PPIH). This led to an increase in clinical
attention to PPIH and the understanding about the epidemiology and contributing
risk-factors is improving. Data from an ongoing study (not published) shows
that the actual prevalence of hypomagnesemia in PPI-using outpatients is 12%
showing that there is a considerable proportion of patients at risk. Moreover,
polymorphisms present in the magnesium transporter TRPM6 (transient receptor
potential 6) increased the chance of PPI users to develop hypomagnesemia by 4
times. It is anticipated that PPIH is caused by the intestinal malabsorption of
Mg2+, but the exact molecular mechanism is speculative. There is some evidence
that PPI*s induce a raise of the pH in the large intestine. This reduces the
fraction of ionized Mg2+ available for uptake by the magnesium transporting
channel TRPM6 which is apically expressed in the colon, the final intestinal
segment absorbing Mg2+.
Study objective
Objective: The primary objective is to determine if the dietary fructan-fiber
inulin is applicable in PPIH. More specific, it aims to (i) improve the
magnesium balance in cases of hypomagnesemic PPI users and (ii) to evaluate if
the use of inulin is accompanied with any unwanted side-effects.
Study design
Study design: This is an observational study that will follow patient serum
Mg2+ values over a period of 57 days. In the study period a number of 4
individual n=1 trials will be conducted with a duration of 14 days each (2 x
trial period with PPI + inulin AND 2 x trial period with PPI only). Each trial
period follows the last suit without a lag phase (please refer to figures 1a +
b).
Study burden and risks
Nature and extent of the burden and risks associated with participation,
benefit and group relatedness: Patients will be addressed individually and
informed about this study. Patients will receive the written information on the
inulin trial and in individual interviews the background and procedures will be
explained. Patients willing to participate, need to sign the standard common
consent form which is included as part of this study protocol.
Burdens:
First: Participants will need to visit the Radboudumc for intake and
blood-withdrawal over a period of 57 days (figures 1a & 1b). The frequency is 2
times in the first 15 days (at t=0d and at t=14d). Each subsequent trial
follows the preceding directly and blood is sampled then subsequently at t=28d,
t=42d t=56). In total the patient will need to visit the Radboudumc 5 times for
blood sampling (if indicated or wanted patients can also donate blood at their
native place/physician to prevent unnecessary travels). Additionally, patients
will be asked to collect 24 hrs urine for Mg2+ and Ca2+ measures. Collected
urine can be delivered at blood sampling or can be sent. Serum Mg2+
surveillance is a prerequisite to join and stay in this study.
Geert Grooteplein 26-28
Nijmegen 6525 GA
NL
Geert Grooteplein 26-28
Nijmegen 6525 GA
NL
Listed location countries
Age
Inclusion criteria
The use of PPIs (protonpump inhibitors, type omeprazol) and having hypomagnesemia as defined by serum Mg2+ < 0.7 mmol/L.
Exclusion criteria
Unstable health conditions, patients that have stopped the PPI, acutely ill patients.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL47262.091.13 |