To prove that sustained clinical remission can be maintained at week 14 with a new dietary strategy that involves only 2 weeks of EEN with Modulen and 22 weeks of an exclusion diet involving selected table foods. We hypothesize that use of EEN for…
ID
Source
Brief title
Condition
- Gastrointestinal infections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
ITT, sustained Corticosteroid-free remission at week 14 (defined as Pediatric
Crohn Disease Activity Index- PCDAI *10 without exposure to systemic steroids).
Secondary outcome
1. ITT steroid-free clinical remission at week 8
2. Microbiome composition difference between groups at week 14
3. Reduction of at least 50% from baseline in fecal calprotectin at week 24 for
patients who did not change their treatment
4. Steroid and biologic free remission at week 24.
5. Need for additional treatment to achieve remission by week 14
6. Transmural healing as assessed by MRE in dietary responsive disease at week
52
7. The proportion of patients who respond with the susceptible genes compare to
those without the susceptible genes
8. Microbiome composition difference between dietary responders to healthy
controls at week 24
Background summary
Exclusive enteral nutrition (EEN) is an established but difficult to perform
method for induction of remission and is not practical or effective for
maintenance of remission. It entails drinking a liquid medical formula for 8
weeks as the sole intake of food. Refusal to use or to adhere to this therapy
is not uncommon and leads to use of other non- dietary strategies in children
including steroids and immunosuppression. Partial enteral nutrition (PEN)
appears to have some benefit in maintenance of remission in adults but
paediatric data are conflicting. There is no prospective pediatric controlled
trial to provide evidence. The Crohn*s Disease Exclusion Diet (CDED) with
partial enteral nutrition has been shown to be effective for induction of
remission in children with mild to moderate disease. We have developed a
maintenance strategy based on the CDED that appears to maintain remission while
allowing increased access to table foods over time.
Study objective
To prove that sustained clinical remission can be maintained at week 14 with a
new dietary strategy that involves only 2 weeks of EEN with Modulen and 22
weeks of an exclusion diet involving selected table foods.
We hypothesize that use of EEN for only 2 weeks followed by partial enteral
nutrition with the CDED diet with PEN will be superior in sustaining
Corticosteroid-free remission by week 14 compare to 8 weeks of EEN followed by
PEN and free diet, and that this remission will be maintained through week 24
while the diet is maintained. From a translational viewpoint, we intend to
compare the effects of dietary therapy on the microbiome, including microbial
function and mucosa associated bacteria, between patients using standard EEN
and free diet and those on modified EEN and CDED with PEN. We will also compare
changes in microbiome to healthy controls, siblings and parents. We further
hypothesize that the CDED will promote butyrate producing species while EEN
will reduce these species.
Study design
This is a multicenter, open-label, randomized controlled trial. The study will
be performed in 5 countries in and outside the EU. The study duration is 52
weeks. Children in group 1 will follow a diet during 24 weeks. Children in
group 2 will receive standard of care treatment during 8 weeks (with gradual
reduction of EN to week 12)
Intervention
Group 1 will receive a short course (14 days) of EEN followed by partial
enteral nutrition, providing 50% of their needs from Modulen along with CDED
for 6 weeks (total 8 weeks); this will be followed by CDED phase 2 with 25% of
the patients* dietary needs from Modulen for an additional 6 weeks (weeks
9-14). Starting at week 15, patients will continue to CDED phase 3 (maintenance
phase) with 25% of dietary needs from Modulen.
Group 2 will receive Standard EEN for 8 weeks using Modulen, followed by free
diet with gradual reduction of Modulen to 25% PEN by week 12.
Study burden and risks
The burden in this study consists of a long-term dietary adjustment, which can
be a burden. We attempt to reduce this burden to the minimal amount by
providing clea instructions and sample recipes. In addition, participants must
answer a number of questionnaires during the study, something that takes up
their time. Urine collection and MRE at week 52 is something that would not be
performed during standard care. If the child's own doctor decides on a
colonoscopy, we will ask for ileal washes and additional biopsies. This is
optional. All these (additional) actions take time and may be a burden but do
not pose a substantial risk to the participant of the study. Also, following
the diet itself does not entail any additional risks.
The resutls on which this study is based are promising and there is a good
chance that this dietary adjustment will allow children to remain
complaint-free (in remission) for longer and.or postpone additional treatments
with steroids and biologicals. In current practice, the CDED (according to
Levine et al, Gastroenterology 2019) is well tolerated, allowing induction of
remission. Motivated parents even continue the diet after end of the "schedule"
because of the positive effects and the "minimal" effort they have to make by
excluding certain table foods. In addition, standard treatment (EEN) for
induction of remission is foten poorly tolerated and/or refused by children.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
For Patients
1. Established diagnosis of Crohn's disease.
2. Patients with mild to severe active Crohn's disease (15*PCDAI*47.5)
3. Ages 8-18
4. Duration of disease * 36 months
5. Active inflammation (CRP*0.6 mg/dL or ESR*20 or Calprotectin*200 mcg/gr
during screening
6. Patients with B1, P0 uncomplicated disease at enrollment
7. Patients with disease defined as L1, L4, L3 or L2 limited to cecum,
ascending or transverse colon or L2 with left sided disease with terminal ileum
or small bowel involvement in the past by the Paris classification (patients
with macroscopic disease)
8. Signed informed consent
Inclusion criteria comments:
1. Patients with stable medication (IMM/5ASA) use or no medication use for the
past 8 weeks may be enrolled.
2. Patients with few aphthous ulcers in the rectosigmoid only can be enrolled
as L2
Exclusion criteria
For patients
1. Patients with very mild disease (PCDAI 12.5-15) or very severe disease
(PCDAI >47.5)
2. Pregnancy
3. Patients who have disease confined to the colon involving the descending
colon, rectum or sigmoid colon and no prior history of small bowel involvement
4. Patients who have active extra intestinal disease (such as arthritis,
uveitis, pyoderma gangresom, erythema nodosum, etc.)
5. Patients with complicated disease (B2, B3)
6. Patients with recent onset use of an immunomodulator <8 weeks, or dose
change in past 8 weeks.
7. Patients with past or current use of biologics, or patients who currently
use systemic steroids or used steroids over the last 8 weeks
8. Patients who have active perianal disease (active fistula or abscess)
9. Patients who have positive stool cultures with relevant pathogens, or
positive tests for parasites or C. difficile. Stool tests are mandatory only if
diarrhea is present.
10. Patients with fever > 38.3
11. Documented milk protein allergy
Exclusion criteria comments:
1. Aphthous stomatitis is not an exclusion criterion. Isolated aphthous ulcers
of the rectosigmoid need not be excluded as left sided L2 only
2. Patient may receive a stable dose immunomodulator or start thiopurines at or
after week 4 or Methotrexate at week 6, since the effect of thiopurine starts
after 8 weeks and that does not affect the primary endpoint remission at week 8.
3. Patients are allowed use of Omeprazole if ulcers or erosions are present in
the stomach or duodenum.
4. Patients may receive antibiotics for intercurrent infections for up to 10
days with the exception of quinolones, metronidazole, rifaximin or oral
vancomycin; antibiotics used must be registered in the CRF.
5. Patients with skin tags or fissures can be enrolled.
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 | NCT02843100 |
| CCMO | NL73108.018.20 |