Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03171246 |
| Other study ID # |
GN17GA213P |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
October 23, 2017 |
| Est. completion date |
May 31, 2023 |
Study information
| Verified date |
January 2024 |
| Source |
NHS Greater Glasgow and Clyde |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Crohn's disease (CD) is a chronic inflammatory condition of the gut with severe
complications. There is strong evidence to suggest that diet and gut bacteria are key
components in the onset, perpetuation and management of CD.
An 8-week exclusive liquid diet (EEN) without any normal food is the best treatment for
paediatric CD. The mode of action of EEN remains unknown, but according to recent
publications, the modulation of the gut bacteria drives its therapeutic properties. While
successful, EEN is a challenging therapy to follow. Half of the paediatric EEN patients will
require a nasogastric tube to support treatment, its use in adults is limited, and the need
for a more palatable diet is very well described. Based on these findings, a non-liquid and
more acceptable dietary treatment was recently devised called CD-TREAT (Crohn's Disease
TReatment-with-EATing) diet. CD-TREAT, which is a solid food-based diet designed to replicate
the nutrients and food ingredients composition of EEN, was recently tested in healthy adults
and a rat model of colitis. In order to pilot CD-TREAT diet as a CD induction treatment, 10
children and 10 adults with active luminal CD will be recruited. Once consented, baseline
blood, urine and faecal samples will be collected and the CD-TREAT prescribed for a maximum
of 12 weeks. Another 3 blood, urine and faecal samples will be requested during the 12 weeks.
All the foods/meals of the CD-TREAT diet will be purchased and delivered to the participants'
house by the researcher and the meals which need cooking will be pre-prepared by a
sub-contracted catering company. Blood and faecal inflammatory biomarkers will be measured,
the disease activity assessed with routinely used clinical indices and the faecal bacteria
and its metabolites characterised.
Description:
Children and adults who are eligible to participate will be identified by medical staff. A
member of the clinical team will briefly inform potential participants about the study via
the phone, via e-mail, or at the clinic. After the end of the clinical appointment and if the
patient and/or the parent/carer are agreeable, a member of the clinical team will introduce
the eligible participants to the researcher who will explain the study in full and answer any
questions they might have. During this meeting, the researcher will discuss the specific
aspects of dietary treatment with CD-TREAT and will inform participants that urine, blood and
faecal samples will be collected to try and determine the type of bacteria which may be
associated with gut inflammation, and their metabolites, and whether these can predict
response to treatment. The researcher will also ask for permission to collect medical
information from the participant's medical records. If they are interested in taking part,
they will be given detailed written information (including an age-appropriate information
leaflet). The information pack will also invite the family to contact the researcher at any
time if they require further information.
As there is a very narrow time window between identification of eligible participants and
consent to participate to the study, and considering the need for immediate initiation of
treatment in patients with active disease, it is anticipated that signed consent to join the
study will be obtained on the same day of receiving information about it; however there will
be subsequent opportunity to review this decision. Consent will only be taken if participants
feel they have had adequate time to make this decision, and no pressure will be applied in
any way.
This will also facilitate the completion of a health check questionnaire, baseline clinical
review, medication and disease history, quality of life assessment, anthropometry
measurements, collection of baseline research bloods (extra volume at the time of routine
clinical tests (no additional venepuncture required). At this point the participant will be
asked to take a stool and urine sample collection kit at home and a suitable date/time to
collect the baseline samples will be arranged. The actual intervention will start
approximately 24 hours later in order to allow the participants enough time to consider and
discuss the study with their relatives, decide whether they would like to continue or drop
out and start the standard induction treatment as deemed necessary by the treating clinical
team. Furthermore, this 24 hour time window will enable the researcher to collect baseline
samples before the initiation of the CD-TREAT dietary treatment.
Where appropriate, the assent of the child will be sought (usually under age 11 or younger),
and in the case of young adults who would be deemed able by a member of the clinical team to
consent on their own part (usually age 12 or older), consent from the young person will be
accompanied by the parent/carer giving signed assent before they can join the study; to
ensure both child and parent/carer are willing and happy to take part. For children unable to
give written consent/assent, the parent/carer will be asked to explain the study in terms
that the child can understand and the carer will sign consent on their behalf.
It will also be made clear at this stage, on information sheets and throughout the study that
participants can withdraw from the study at any time without it affecting their routine care
in any way. Continuation of CD-TREAT dietary advice and provision of CD-TREAT foodstuffs is
dependent however on continuation in the study. Discontinuation of study participation after
commencement of CD-TREAT would therefore involve return to standard induction treatment at
the discretion of the treating clinical team.
Throughout the study recruited participants will be asked to provide urine, faecal and blood
samples (an additional small tube of blood when they are having routine bloods at clinical
appointments) on a maximum of 4 occasions. In addition, these time points will include
clinical review, quality of life assessment and anthropometry measurements.
Participants will also provide some dietary information reflecting their compliance to
CD-TREAT diet.
CD-TREAT Intervention:
All patients on the CD-TREAT diet will be supplied with an individually tailored,
dietitian-devised diet, consisting of ordinary foods, but custom-designed to recreate the
nutritional content and ingredients of EEN. The dietary intervention will be overseen by
qualified dieticians including a National Health Service (NHS) research dietician. The energy
content will be tailored to adult participants' total energy expenditure and physical
activity level calculated by the World Health Organisation (WHO) set of equations or will be
calculated for each child to meet their estimated average requirement (EAR) for age. Food and
instructions for those patients on CD-TREAT will be supplied directly to them by the
researchers on the day following recruitment. Foods which need cooking will be prepared by a
sub-contracted (food handling and hygiene certified) catering company and will be delivered
to the participants' house every 2-3 days. The rest of the foods will be delivered to the
participants' house every week. Participants will initially receive the modified diet for a
period of 8 weeks, similar to the duration of an EEN course. The researchers will instruct
the participants and their carers on how to follow the diet and how to record their dietary
intake during the intervention. Research follow-up visits will coincide with the
participants' clinical follow-ups (Week 2: phone review; Weeks 4 & 8: hospital visit). These
follow up appointments will include collection of research bloods as an extra aliquot to
their routine clinical tests (no additional needle insertion is required), clinical review,
quality of life assessment and anthropometry measurements. At these appointments, the
researchers will give the participants a stool and urine sample collection kit to take home
and will arrange a suitable date/time to collect the faecal and urine sample.
Response to treatment will be assessed according to clinical review, CD activity score and
measurements of established biomarkers in faeces and blood (e.g. faecal calprotectin). The
primary endpoint will be clinical response (Adults: HBI fall≥3; Children: wPCDAI fall≥17.5)
or clinical remission (Adults: HBI<5; Children: wPCDAI<12.5) at 8 weeks; while secondary
endpoints include reduction in faecal calprotectin and blood inflammatory markers and changes
in anthropometry. All patients will be under close follow-up. No new CD-related medications
will be allowed during the pilot study, however if patients' disease activity is
deteriorating at any point during the study or there is no response at 4 weeks, patients will
be eligible to discontinue CD-TREAT diet and commence medical/surgical treatment as deemed
necessary by the treating clinical team. Those participants will still be encouraged to
provide stool, blood and urine samples at intervention exit. For those demonstrating
response, all background CD-related medication dosages will remain stable unless a subject
develops specific drug-related side-effects, blood monitoring abnormalities or blood drug
levels requiring alteration. Those patients who experience clinical response but not clinical
remission at 8 weeks will be given the opportunity to stay on CD-TREAT for a further 4 weeks.
At the end of this period (12 weeks post CD-TREAT initiation) they will be asked to provide
the last stool and urine sample and they will have the last follow-up appointment including
collection of research bloods, clinical review, quality of life assessment and anthropometry
measurements.
