Clinical trial NCT04596566: Modeling Patient Response to a Therapeutic Diet in Crohn's Disease
Official title: Can Personalized Diet Therapy Favourably Impact Disease Severity in Patients With Crohn's Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Crohn Disease
Lead sponsor: University of Calgary
Sponsor class: OTHER
Collaborators: name: Crohn's and Colitis Foundation
name: University of Alberta
name: University of Guelph
name: University of British Columbia
name: Alphabiomics
name: University of Birmingham
First posted: 2020-10-22
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: BACKGROUND: There is an urgent need to understand the role of therapeutic dietary interventions on the treatment of inflammatory bowel disease (IBD). Although nutritional observational studies have examined associations between diet and the development of IBD, the relationship between dietary components and disease relapse is lacking. Despite the lack of a well-defined relationship between dietary determinants and disease relapse, patients with IBD frequently have a strong belief that diet has a key role in controlling the course of their disease, and maybe a trigger of disease relapse. This proposed randomized controlled trial (RCT) explores the efficacy of a Crohn's Disease (CD) Therapeutic Dietary Intervention (TDI) compared to conventional management (CM) to induce steroid-free clinical remission at week 13 in patients with active, mild-to-moderate luminal CD. For asymptomatic patients with active disease, efficacy of the diet will be explored by using fecal calprotectin and sonographic findings

Rationale: Our team of investigators recently compared a representative healthy population to patients with CD and identified CD patients have: lower intakes of polyunsaturated and monounsaturated fats and multiple micronutrients (vitamins C, D, thiamine magnesium, phosphorus, zinc, potassium), and; few patients with CD met criteria for an anti-inflammatory dietary pattern. Since the diet is a modifiable potential risk factor for disease recurrence in IBD, there is a strong rationale for the investigation of diet on disease course. Additionally, patients have expressed strong interest in identifying the relationships between diet and disease, therefore assigning priority to this theme is an opportunity to advance patient-oriented care.

Detailed description: OBJECTIVES:

Primary objectives

A) Symptomatic patients at the time of recruitment: Harvey Bradshaw Index (HBI) \>5 to \<16

1. To compare the proportion of patients in each study group at week 13 who are in corticosteroid-free (CF) clinical remission as measured by a Harvey Bradshaw Index (HBI) of \<5 (primary endpoint)
2. To compare the proportion of patients in each study group at week 13 who are in biochemical remission as measured by a fecal calprotectin (FCP) of \<250ug/g (primary endpoint).

B) Asymptomatic patients with active disease at the time of recruitment: Harvey Bradshaw Index (HBI) \<5

1. To compare the proportion of patients in each study group at week 13 who are in biochemical remission as measured by a fecal calprotectin (FCP) of \<250ug/g (primary endpoint).
2. To compare the proportion of patients in each study group at week 13 who are in clinical remission as measured by sonographic findings of inflammation (Bowel Wall thickening ≤ 3mm).

Secondary Hypothesis: The aim of the secondary objectives are to examine whether the dietary intervention has a significant effect on the gut microbiota and SCFAs in patients and whether this is associated with the intervention and disease recurrence at or before 13 weeks. The aim is also to examine whether the intervention has a significant effect on health-related quality of life.

* To identify the presence of within and between-group differences in microbial diversity, microbial composition, and abundance of short-chain fatty acids (SCFA) and SCFA-producing bacteria at baseline and 13weeks.
* To identify the presence of within and between-group differences in fecal SCFA concentrations at baseline and 13 weeks. To compare the proportion of patients in each study group at week14 that achieve clinical response (decrease in HBI\>3points)

METHODS:

Randomized controlled trial design: This 3-year study, investigator-blinded, RCT (N=102) at the University of Calgary (UoC). Eligible participants will be randomly allocated in a 2:1 ratio to either the intervention group (CD-TDI) or conventional management (CM) alone (i.e., control group) for 13 weeks.

Conventional Management (Control) Group: CM patients will meet with the RD at baseline, week 7 and week 13 to complete their 24 hour food recall twice on different days of the week, followed by a phone few days after the visit to complete the second part of the recall. They will be advised to follow their habitual diet and will be offered the dietary intervention at 14 weeks if they are still experiencing a disease flare.

Therapeutic diet Intervention ( CD-TDI )Group : Patients receiving CD-TDI will be offered patient-centered counseling for 12 weeks by a Registered Dietitian (RD) trained in the CD-TDI protocol with the goals of (a) identification and treatment of malnutrition if present, (b) targeted treatment of macro- and micronutrient deficiencies using whole foods;(c) increasing adherence to CD-TDI (d) multivitamin adherence and (e) reduced exposure to dietary antigens (e.g., maltodextrin, carrageenan, other food additives). They will receive a5 face-to-face appointment every 3 weeks with the study RD, and all other weekly appointments, which are 8 in number will be completed by phone.

Eligibility criteria: Inclusion Criteria:

* (a)≥18 years;
* (b)diagnosis of mild-to-moderate luminal ileal, ileo-colonic or colonic CD
* (c) active disease with Harvey Bradshaw Index (HBI) \<16 at time of recruitment;
* (d) for active symptomatic patients (HBI \> 5 to \<16) evidence of endoscopic disease activity within six months of enrolment (presence of ulceration ≥5mm ) and for active asymptomatic patients (HBI \<5) sonographic findings of intestinal inflammation ≥3mm of bowel wall thickening)
* (e) biomarker evidence of inflammation fecal calprotectin at enrolment (FCP

  * 250microg/g).
* (f) \< OR = 1 small bowel resection,
* (g) ability to provide informed consent

Exclusion Criteria:

* HBI \>16 at time of recruitment;
* (b) fecal calprotectin \< 250 microg/mg within 1 month prior to study enrollment;
* (c) patients with upper GI tract CD;
* (d) evidence of perianal or fistulizing disease; (
* e) \>1 bowel surgery;
* (f) significant chronic disorders such as cardiac disease, renal failure, active pulmonary disease (these factors may influence dietary intake),
* (g) any psychiatric or neurocognitive comorbidity that would limit ability to follow an CD-TDI
* (h) laxative or antibiotics in the past 3 months and
* (i) presence of ostomy.

Primary outcomes:
measure: Fecal calprotectin: Change is being assessed.
timeFrame: baseline, 7 and 13 weeks.
measure: Harvey Bradshaw Index (HBI): Change is being assessed
timeFrame: baseline, 7 and 13 weeks.
measure: Bowel wall thickness on sonographic findings and Fecal calprotectin: Change is being assessed.
timeFrame: baseline, 7 and 13 weeks for fecal calprotectin and baseline and week 13 for sonographic findings
Secondary outcomes:
measure: Fecal Microbiota Sequencing: change is being assessed.
timeFrame: baseline, 7 and 13 weeks
measure: Short chain fatty acids: Change is being assessed
timeFrame: baseline, 7 and 13 weeks
measure: Health related quality of life: Change is being assessed.
timeFrame: baseline, 7 and 13 weeks
measure: Subjective global assessment: Change is being assessed
timeFrame: baseline, 7 and 13 weeks
measure: Dietary intake: Change is being assessed
timeFrame: baseline, 7 and 13 weeks
measure: Sedentary time: Change is being assessed
timeFrame: Baseline and week 13
measure: CRP: Change is being assessed
timeFrame: Baseline and week 13
measure: Ferritin: Change is being assessed
timeFrame: Baseline and week 13
measure: Albumin: Change is being assessed
timeFrame: Baseline and week 13
measure: Vitamin D: Change is being assessed
timeFrame: Baseline and week 13
measure: Cr: Change is being assessed
timeFrame: Baseline and week 13
measure: Electrolytes: Change is being assessed
timeFrame: Baseline and week 13
measure: Hb: Change is being assessed
timeFrame: Baseline and week 13
measure: Platelet: Change is being assessed
timeFrame: Baseline and week 13
measure: WBC: Change is being assessed
timeFrame: Baseline and week 13
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: TRW building, Foothills, University of Calgary
state: Alberta
Study officials:
affiliation: University of Calgary
name: Maitreyi Raman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Raman M, Ma C, Taylor LM, Dieleman LA, Gkoutos GV, Vallance JK, McCoy KD, Lewis I, Jijon H, McKay DM, Mutch DM, Barkema HW, Gibson D, Rauch M, Ghosh S. Crohn's disease therapeutic dietary intervention (CD-TDI): study protocol for a randomised controlled trial. BMJ Open Gastroenterol. 2022 Jan;9(1):e000841. doi: 10.1136/bmjgast-2021-000841.