Main objective: to assess whether CDED is superior to corticosteroids, in terms of endoscopic response, in patients with mildly to moderately active, luminal CD.
ID
Source
Brief title
Condition
- Gastrointestinal infections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint: endoscopic response at week 16, without corticosteroids or
further therapeutic intervention, assessed by a centralized, anonymous and
blinded, double lecture panel of panenteric PillCam Crohn*s Capsule (PCC).
Endoscopic response is defined by a decrease of at least 50% in the Lewis score
for patients with small bowel CD, decrease of SES-CD of at least 50% in
patients with colonic CD and both of these in patients with small bowel and
colonic CD, compared to baseline
Secondary outcome
Compare between the 2 arms of the trial:
- (Steroid-free) clinical remission (HBI <5) and response (a decrease of at
least 3 points in HBI)
- (Steroid-free) clinical remission (CDAI <150) and response (a decrease of at
least 70 points in CDAI)
- Need for further therapeutic intervention (i.e., steroids,
immunosuppressants, new biologic or surgery)
- Decrease of fecal calprotectin of at least 50%, off steroids.
- Fecal calprotectin of less than 250 µg/g, less than 100 µg/g and less than 50
µg/g
- CRP serum level
- Median HBI, calprotectin and CRP
- Endoscopic remission as defined as Lewis score <135 in the small bowel and/or
SES-CD=0-2 in the colon, without further therapeutic intervention (surgery,
biologics or dietary intervention)
- Endoscopic response and remission graded by Eliakim scores
- Segmental endoscopic response and remission
- Body weight, arterial pressure and fasting serum glucose
- Gut microbiota composition (PCR 16s, PCR 18S for fungi and protists,
metabolomics and shotgun metagenomics) at baseline, week 6 and week 16
- Complianceto corticosteroid treatment: Medication Adherence Report Scale
- Compliance to CDED:
- o Dietary habits questionnaires
- o 72-H food diaries
- Safety will be assessed by the adverse events, either severe or not, and the
SUSARQuality of life will be assessed by short IBDQ
- Work productivity and activity will be assessed by the WPAI questionnaire
Background summary
Current medical treatment of Crohn*s disease (CD) consists of immunosuppressive
drug therapy (corticosteroids, azathioprine, methotrexate, anti-TNF monoclonal
antibodies). These agents control symptoms of CD in most patients but their
withdrawal leads to disease relapse. They are also associated with serious
adverse events, such as infections and lymphoma (1, 2). Future CD drugs are
small molecules or biologics that antagonize pro-inflammatory cytokines or gut
homing of lymphocytes. They have similar safety issues as the immunosuppressive
agents currently in use.
Epidemiological and experimental studies have suggested that diet plays an
important role in CD pathophysiology. The pathogenesis of CD appears to involve
alteration of the microbiome as well as a breakdown in barrier function with
defective bacterial clearance (3). Changes in dietary intake and
industrialization may explain the rise in CD incidence over the past decades.
These changes of food may induce alteration in the microbiome and impair the
barrier function of the mucous layer and intestinal epithelium, which then
allows adherence and immune triggering by the altered mucosal microbiome (3).
Exclusive enteral nutrition (EEN), consisting of a liquid formula diet while
avoiding any other oral intake, has been used for decades to treat active CD in
pediatric and adult patients. It improves symptoms and heals endoscopic lesions
better than corticosteroids (4, 5, 6). EEN has no medical side effects, and is
currently recommended as a first-line treatment in pediatric CD (7). However,
long-term compliance of EEN is poor.
Crohn*s disease exclusion diet (CDED) is a new treatment of active CD. It is a
whole-food diet coupled with partial enteral nutrition. It is aimed to restore
intestinal barrier and improve microbiota composition by exclusion of dietary
components that contribute to its dysfunction (3). A recent randomized,
controlled trial has shown that CDED was equally effective and better tolerated
than exclusive enteral nutrition in pediatric CD patients (8). Importantly it
was also highly effective for reduction in inflammation and partially corrected
dysbiosis. This is the first demonstration of the efficacy of an exclusion diet
in CD. Yet, there are several questions remaining: does CDED have the same
efficacy in adults, what is the effect on endoscopic lesions, and what is the
relative efficacy of CDED as compared with current treatment (9). Crohn*s
disease affects children but the majority of patients are adults. It is
mandatory to ensure that CDED does not only relief symptoms, but also heals the
mucosa.
In this randomized clinical trial, we aim to compare the tolerability and
efficacy of CDED coupled with PEN with corticosteroids, in inducing endoscopic
response.
Study objective
Main objective: to assess whether CDED is superior to corticosteroids, in terms
of endoscopic response, in patients with mildly to moderately active, luminal
CD.
Study design
This is a multicentre, open-label, comparative, randomized, 2:1, controlled,
single-blind, superiority
Intervention
Groep 1 ontvangt het Crohns Disease Exclusie Dieet plus drinkvoeding
Groep 2 ontvangt corticosteroiden en kan daarna voor het Crohns Disease
Exclusie Dieet kiezen.
Study burden and risks
So far, no risk associated with the exclusion diet, exclusive, partial enteral
nutrition or CDED for Crohn's disease has been identified. Yet, CDED is
burdensome because it consists in the avoidance of many food.
PCC carries the risk of intestinal obstruction or perforation if the capsule is
blocked above an intestinal stricture. This risk can be avoided by the
systematic use of the patency capsule prior to administration of the real
capsule. Each of the two panenteric capsule endoscopies needs bowel
preparation. However, patients whose endoscopic lesions are confined to the
small bowel at the first PCC, will be prepared by only 1000 mL of PEG, 30
minutes after the second PCC. Moreover, PCC caries the risk of delayed or no
excretion of the capsule and the risk of lesion or mucosal bleeding.
* The risk level of the study is B (= somewhat higher than the risk of standard
medical care).
The potential benefit of the trial is that of an improvement of CD endoscopic
lesions with dietary therapy that has no known side effects. Multiple studies
have shown that healing of endoscopic lesions was associated with long-term
beneficial outcomes.
Avenue Claude Vellefau 1
Paris 75010
FR
Avenue Claude Vellefau 1
Paris 75010
FR
Listed location countries
Age
Inclusion criteria
- Patients aged 16 to 70 years,
- With mild to moderate, luminal, active CD, defined by a HBI of 5 to 16,
involving the small bowel, and/or the colon
- Not treated with corticosteroids at baseline
- Patients either naïve or previously exposed to a maximum of two classes of
biologics or currently receiving a biologic therapy, and exposed to a maximum
of two classes of biologic therapy, including the current one
- Patent small bowel as assessed by the patency capsule
- Active endoscopic lesions, as defined by Lewis score >= 225 in the small bowel
and/or SES-CD>= 4 in the colon. The eligibility of the patient will be
determined by the site investigator and a central reader.
Exclusion criteria
- Inability to follow the CDED during 16 weeks.
- Prior intolerance to corticosteroids.
- Ongoing infections, evolving virus diseases.
- Live vaccines.
- Arthritis or uveitis as main presenting symptoms.
- Patients with severe and/or predominant rectal or perianal disease.
- Heavy smokers (more than 10 cigarettes per day).
- Infliximab, adalimumab, methotrexate or azathioprine initiated less than 3
months before inclusion in this trial.
- Vedolizumab, ustekinumab initiated less than 6 months before inclusion in
this trial.
- Change in methotrexate, azathioprine, infliximab, adalimumab, vedolizumab or
ustekinumab dosage less than 3 months before inclusion.
- Pregnant or lactating women
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 | NCT05284136 |
| CCMO | NL82030.018.22 |