The primary objective is to evaluate in the two targeted populations (i.e. CD and self-reported NCGS subjects):1) the safety profile of BL NCC 2705 2) the gastro-intestinal (GI) tolerability of BL NCC 2705
ID
Source
Brief title
Condition
- Food intolerance syndromes
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1) Adverse Events (AE) incidence, type, severity and causal relationship to the
investigational product
2) GI scores from a Visual Analogue Scale (VAS) over both treatment periods at
home (i.e. from day 1 to day 3) for each symptom of interest (i.e. 1) nausea,
2) vomiting, 3) diarrhea, 4) audible bowel sounds, 5) flatulence, 6) abdominal
cramping)
Secondary outcome
1) Concentration of serpin in duodenal aspirates
2) Concentration of BL NCC 2705 in duodenal aspirates
3) Inhibition of the elastase activity in duodenal aspirates
4) Concentration immunogenic (33-mer) gluten-derived peptides in duodenal
aspirates following a 3g gluten containing meal
5) Inhibition of glutenasic activity in duodenal aspirates
6) Urinary excretion of immunogenic (33-mer) gluten-peptides following the
gluten-containing meal
Background summary
The rationale of the present clinical study is to generate proof of concept for
the development of BL NCC 2705 as a complementary treatment to gluten-free diet
(GFD) in subjects with gluten-related disorders still experiencing symptoms due
to accidental intake of hidden gluten.
BL NCC 2705 is expected to counteract the negative effects of hidden gluten by
a dual mechanism of action, consisting of a) anti-inflammatory properties
deriving from the inhibition of duodenal elastase activity and b) reduced
production of immunogenic and toxic gluten peptides deriving from the
inhibition of the glutenasic activity of the intestinal proteases by probiotic
produced serpin.
Study objective
The primary objective is to evaluate in the two targeted populations (i.e. CD
and self-reported NCGS subjects):
1) the safety profile of BL NCC 2705
2) the gastro-intestinal (GI) tolerability of BL NCC 2705
Study design
This trial is a multicenter, double blind, randomized, placebo controlled, 2 by
2 cross-over design. Recruitment of participants takes play by Maastricht
University, and the study will also be conducted by Maastricht University.
VieCuri Medisch Centrum performs one procedure (catheter placement) and is
involved in sample analyses.
Intervention
The active product is a food supplement for human consumption. It contains
1.0x10^10 cfu of the probiotic strain Bifidobacterium longum NCC 2705 (BL
NCC2705) premixed with a carrier which is maltodextrin. The placebo product
contains only maltodextrin.
The products will be given to participants for a period of 4 consecutive days.
Participants will have to ingest test products twice daily.
Study burden and risks
As this is a proof of concept study foreseeing a short-lasting administration
of BL NCC 2705 to gluten sensitive subjects in symptomatic remission,
participants will not receive any direct clinical benefit. However, the study
targets an important unmet medical need * i.e. the persistence of symptoms in
gluten sensitive subjects following a gluten-free diet * and is based on a
rigorous and methodologically robust experimental approach that is expected to
provide solid evidence on the mechanism of action of the product. This will be
instrumental to the optimization of the subsequent phases of the clinical
development plan.
Based on the nature of BL NCC 2705 (healthy infant-derived probiotic) and on
the conclusion of the internal Nestlé Research Center safety evaluation (see
Investigators* Brochure), no significant safety concern is expected from a
short-term exposure to the investigational product (2 cycles of 3 and * days
per subject of, respectively, active product or placebo in a cross-over
design).
During the entire duration of the study all the adverse events will be
thoroughly collected and reported. In addition, gastrointestinal tolerability
will be explored through a self-assessment tool constituted by visual analogue
scales measuring the intensity of possible gastrointestinal symptoms.
As part of the experimental model, two single administrations of gluten (one
per treatment cycle) are foreseen to the purpose of assessing the effects of
the investigational product on gluten digestion. This acute exposure to gluten
is not expected to be harmful to the subjects because a) a low dose will be
used (i.e. 3g, which is within the amount conventionally considered as
gluten-contamination and b) the two administrations will be made with a minimum
of 18 days apart. It has been shown that many days or weeks of continuous
intake of even higher doses are needed to re-activate the clinical,
histological and serological manifestations of gluten intolerance.
The experimental technique foresees the positioning of a naso-duodenal catheter
that will stay in place for 7 to 8 hours. Each subject will undergo this
procedure twice. The catheter position can be controlled under direct
endoscopic view or by fluoroscopic assessment following the procedure. Both
options will be proposed and discussed with the subjects. Endoscopy is a
routine and well standardized medical procedure that can cause some discomfort
but is devoid of any relevant complications.
Although there's no direct benefit for the participants, the benefit/risk
assessment is judged as overall favorable in light of the low likelihood of
relevant safety issues, the robustness of the experimental design and the
relevance of the evidence that the study is expected to generate in terms of
potential contribution to addressing an important unmet medical need.
Avenue Nestle 55
Vevey CH-1800
CH
Avenue Nestle 55
Vevey CH-1800
CH
Listed location countries
Age
Inclusion criteria
1. Willing and able to sign written informed consent prior to trial entry
2. Male or female adults at a minimum age of 18
3. For NCGS: self-reported gluten sensitivity on gluten free diet for at least 6 weeks with self-reported significant symptomatic improvement
4. For CD: confirmed serologic and histologic diagnosis of CD and on GFD for at least 12 months with self-reported significant symptomatic improvement
5. Body Mass Index (BMI) within the range 18 * 30 kg/m2
6. Willing and able to comply with study procedures and restrictions
7. In good health as determined by a medical history and medical examination
Exclusion criteria
1) Documented IgE-mediated food allergy
2) Subjects following an overly imbalanced or restrictive diet as per nutritional advice
3) Concurrent systemic disease and/or laboratory abnormalities considered by investigators to be detrimental for the participants safety or potentially interfering with the study procedures and/or study outcomes
4) Concurrent organic GI pathology other than benign polyps, diverticulosis, hemorrhoids, lipomas and melanosis coli
5) Previous abdominal surgery with the exception of hernia repair, appendectomy, caesarian section, tubal ligation, hysterectomy, hemorrhoidectomy
6) Patients who received antibiotics in the previous 2 weeks
7) women of childbearing potential not willing to use an effective contraception method
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 |
|---|---|
| ClinicalTrials.gov | NCTnrzalbinnen2wekenwordentoegewezen |
| CCMO | NL65701.072.18 |