In the current study we will attempt to evaluate if the diet, termed the UC Diet (UCD), can improve outcomes when administered with a 5ASA regimen to pediatric patients with mild-moderate UC, through a single blinded multinational RCT.
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Remission defined as PUCAI<10 at week 6
Secondary outcome
Clinical Secondary End Points:
- Response defined as a drop of PUCAI at least 10 points or remission
(intention to treat) week 6 .
- Mean/median change in Calprotectin at week 6
- Sustained steroid & biologic free remission week 12
- Need for topical therapy by week 12
- Change in UCDEIS at week 12 ( optional)
- Tolerance to diet defined by withdrawal from the study because of
difficulties with the diet.
Translational Secondary End Points:
- Changes to the microbiome: diet vs. no diet
- Change in microbiome: remission vs. failures
- Short chain fatty acids in stool by group week 6
Background summary
Recent evidence suggests that environmental factors and diet in particular may
play an important role in IBD pathogenesis, with the strongest evidence to date
for Crohn*s disease. Understanding of these processes facilitated development
of effective dietary therapies for patients with CD. To date, there is no
proven dietary intervention that may help patients with ulcerative colitis
(UC). On the microbiota side, UC is characterized by decreased production of
short chain fatty acids (SCFA) and increased Proteobacteria and
sulfide-reducing bacteria ( SRBs). From the host*s perspective, a decrease in
goblet cells and mucin production coupled with a permeable mucous layer is
demonstrated in UC. Each of these observations can be linked to factors found
in Western diet that may promote and accelerate intestinal inflammation. As an
example, soy and casein have been shown to exacerbated dextran-sodium sulfate
(DSS) colitis in mice and dairy fat was shown to induce colitis in a rodent
model as well.
The PIBD research center at WMC has developed a diet (UC Diet, or UCD) based on
restriction and addition of dietary components that may affect the host mucous
layer or microbiome, based on these observations. This diet is rich in fruits
and vegetables but reduces exposure to certain animal-based sources of protein
and fat while favoring other animal sources of protein and healthy oils.
In two ongoing pilot trials to evaluate efficacy in patients with mild to
moderate UC who have failed induction on 5ASA therapy or relapsed on 5ASA (
5ASA failures), this led to a clinical response in 17/19 (88%) and a
steroid-free clinical remission in 9/19 (47%) of treatment courses in children
and 3/6 (50%) in adults (2 with complete mucosal or near complete healing after
8 weeks). These results imply that diet could play a more important role in
induction of remission than currently appreciated.
*
Study objective
In the current study we will attempt to evaluate if the diet, termed the UC
Diet (UCD), can improve outcomes when administered with a 5ASA regimen to
pediatric patients with mild-moderate UC, through a single blinded
multinational RCT.
Study design
This will be a 12 week, single blinded RCT in children and adolescents with
mild to moderate UC comparing 5ASA (recommended dosing 60-75 mg/kg/day; minimum
2.5 maximum 4 grams/day) with fiber restriction for 6 weeks followed by free
diet (Group 1) to 5ASA with UCD for 6 weeks, followed by the step down UCD for
the next 6 weeks.
Intervention
Current clinical practice is to reduce exposure (now withhold fiber) to fiber
during active bleeding and diarrhea and to gradually increase access to grains
fruit and vegetables once patients improve. This practice has no evidence
behind it and was based on common sense. We will compare two dietary
strategies, insoluble fiber reduction via current practice in each site to the
UC Diet. The UC diet will restrict certain sources of animal protein, animal
fat, and emulsifiers and food additives during the 12week period, while
allowing access to fruit, vegetables, and certain grains. It is not a vegan or
vegetarian diet as it contains portions of chicken and eggs. It will be
structured with mandatory foods, foods that are restricted to certain days or
certain quantities, and other foods that are unlimited, to provide better food
related quality of life. Both groups will receive a calcium supplement and
vitamin D supplement for 6 weeks. Dietitians will assess dietary intake of
calories and food groups at week 0 and 6 and will assess compliance by local
analysis of food diaries. Intolerance to diet will be defined as patients
stopping the diet because of difficulty with the diet ( not because of
inadequate response).
Study burden and risks
The burden in this study consists of a dietary adjustment. This burden is
limited by providing clear instructions (on what can be consumed or not) about
the diet and example recipes. Participants must also answer a number of
questionnaires during the study and spend more time than if they did not
participate. On the other hand, the results on which this study is based are
positive and it seems that it could have a beneficial effect on the remission
of the participant. In addition, participating involves no further risks.
Meibergdreef 9 69-71
Amsterdam 1105 AZ
NL
Meibergdreef 9 69-71
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
1. Informed consent
2. Established diagnosis of UC by the Paris classification and Revised Porto
Criteria.
3. Age: 10 - 19 years (inclusive)
4. Mild to moderate active disease, 10 <= PUCAI <=45
5. Extent E2-E4 by the Paris classification
6. Weight >30 kg (ensures that patients who received 5ASA <=2 grams are eligible)
7. Stable medication (IMM/ 5ASA) use or no change in medication use for the
past 6 weeks. Patients who have received topical 5ASA therapy for <10 days and
are active may be included if topical therapy is stopped at enrolment.
8. Patients not receiving 5ASA or using 5ASA<50mg/kg/day
Exclusion criteria
1. Any proven current infection such as positive stool culture, parasite or C.
difficile.
2. Steroids (oral or intravenous) use in the past 3 months.
3. Patients who continue topical 5ASA or steroids after enrolment
4. Use of biologics in present or in past 6 months
5. Use of antibiotics for more than one week in the past 60 days
6. PUCAI >45
7. Acute severe UC in the previous 12 months.
8. Current extra intestinal manifestation of UC.
9. PSC or Liver disease
10. Pregnancy.
11. Vegans or patients unwilling or unable to consume eggs
12. IBD unclassified
Exclusion criteria Comments:
1. Stool culture, parasite or C. difficile will only be measured if the patient
has diarrhea.
2. Patients who have received treatment enemas for 3 weeks or less then 3 days
and are active, can be included but must stop the enemas on the day of
enrolment
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 | NL72407.018.19 |