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Stelara and Diet Trial for Crohn"s Disease

Primary Purpose

Crohn Disease

Status

Not yet recruiting

Phase

Not Applicable

Locations

Israel

Study Type

Interventional

Intervention

Crohn's disease exclusion diet (CDED)

Ustekinumab Injection [Stelara]

About this trial

This is an interventional treatment trial for Crohn Disease

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Informed consent.
Age: 18- 65 years (inclusive).
Established diagnosis of CD
Starting Ustekinumab.
Active disease defined as a CDAI >220, and have an objective measure of disease activity such as an elevated marker of inflammation (elevated CRP >5mg/L or 0.5 mg/dL or calprotectin >150 mcg/g).
Patients must have previously received at least one dose of anti TNF at any time in the past.
Stable medication at least 8 weeks.

Inclusion criteria comments

1. Patients of any weight will be recruited and randomized to the study regardless of their BMI.

Exclusion Criteria:

Pregnancy or lactation
Presence of malignancy
Use of prednisone >20 mg /day
Ongoing use of concurrent medications with a dose change in the previous 8 weeks with the exception of steroids (Patients receiving prednisone 20 mg or less may be enrolled by must be tapered by week 6).
Treatment with an anti TNF in the last 4 weeks.
Patients who will take oral iron oral supplements during the trial (see comment 1 below).
Active infections, tuberculosis, positive stool test for Clostridium difficile toxin.
Active perianal fistula (with discharge, or with an abscess during the past 3 months), rectovaginal fistula.
Fever.
Active extra intestinal disease (arthritis with joint swelling, concurrent liver disease). Patients with skin manifestations and arthralgia may be included.
Smokers who smoke >5 more cigarettes a day (see comment 2 below).
Renal failure.
Uncontrolled diabetes that precludes the diet.
Patients with isolated colonic disease distal to the transverse colon (see comment 3 below).

Exclusion criteria comments

Patients taking oral iron supplements may be enrolled if they discontinue the supplements prior to receiving UST, and are NOT ALLOWED to take oral iron supplements during the first 12 weeks of the trial as the diet reduces oral iron exposure to decrease siderophoric pathobionts (patients are allowed to receive intravenous iron or other oral vitamins during the trial).
Patients who smoke >5 cigarettes per day may be enrolled if they stop smoking from the start of the trial (smoking negates the effect of the diet).
Patients with isolated colonic disease distal to the transverse colon and no history of ileal disease will be excluded to make sure that IBDU is not recruited.

Sites / Locations

Sheba Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Group 1

Group 2

Arm Description

Standard induction regimen of Ustekinumab with the Crohn's disease exclusion diet (CDED)

Standard induction regimen of Ustekinumab as above without diet

Outcomes

Primary Outcome Measures

ITT, steroid free remission

Defined as an improvement in one inflammatory marker (CRP or calprotectin)

Secondary Outcome Measures

Median calprotectin

Reduction in median calprotectin compared to baseline between groups

Intestinal bowel wall thickness

Reduction in intestinal bowel wall thickness compared to baseline between groups for patients with increased bowel wall thickness measured on baseline US.

UST trough level

mean UST trough level between groups.

CDAI between groups

Median decline in CDAI between groups. Crohn's Disease Activity Index (CDAI) range between 0-800

Full Information

NCT ID

NCT04779762

First Posted

February 28, 2021

Last Updated

February 28, 2021

Sponsor

Wolfson Medical Center

Collaborators

Sheba Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT04779762

Brief Title

Stelara and Diet Trial for Crohn"s Disease

Official Title

Stelara and CDED Diet Trial for Crohn"s Disease

Study Type

Interventional

2. Study Status

Record Verification Date

February 2021

Overall Recruitment Status

Not yet recruiting

Study Start Date

January 2022 (Anticipated)

Primary Completion Date

January 2025 (Anticipated)

Study Completion Date

January 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Wolfson Medical Center

Collaborators

Sheba Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

Dietary therapy involving the Crohn's disease exclusion diet (CDED) is an evolving strategy to target the microbiome and innate immunity in order to reduce inflammation and promote healing. The goal of the current pilot study is to evaluate the added benefit of treatment with Ustekinumab combined with CDED in anti TNF exposed patients compared to treatment with Ustekinumab alone in term of achieving remission.

Detailed Description

The induction period is crucial for a patient's response to biologic therapy but also for maintenance of remission, as simple as it sounds, maintenance of remission requires remission. Biological medications using a single monoclonal antibody directed target, seem to be effective only for a segment of the population with Crohn's disease Dietary therapy is highly effective in children and induces remission in approximately 60% of young adults with uncomplicated luminal disease. It was shown to shift the microbiome away from Proteobacteria towards Firmicutes, and to decrease intestinal permeability (i.e improvement in leaky gut). Dietary therapy is widely used in children and both exclusive enteral nutrition (EEN) and the Crohn's disease exclusion diet were highly effective for induction of remission and reduction in inflammation in children in a multinational randomized controlled trial (Levine A, Gastroenterology 2019). Recently a prospective randomized controlled trial in biologic naïve adults demonstrated clinical remission in 62% of adults by 6 weeks (Yanai H, UEG Week 2020). A two week course of EEN in adults was effective for improvement of symptoms and reduction in inflammation (Wall CL Inflamm Intest Dis 2018). Xu et al demonstrated clinical remission in 52 and 47% of two adult cohorts (n=104) using EEN for induction of remission (Xu Y, Therap Adv Gastroenterol 2019). Taken together, these studies suggest that dietary therapy could act as a bridge to biologic effect and have a synergistic effect on the disease.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Crohn Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

Investigator

Masking Description

single blinded

Allocation

Randomized

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Group 1

Arm Type

Experimental

Arm Description

Standard induction regimen of Ustekinumab with the Crohn's disease exclusion diet (CDED)

Arm Title

Group 2

Arm Type

Active Comparator

Arm Description

Standard induction regimen of Ustekinumab as above without diet

Intervention Type

Other

Intervention Name(s)

Crohn's disease exclusion diet (CDED)

Intervention Description

Dietary therapy for Crohn's disease

Intervention Type

Drug

Intervention Name(s)

Ustekinumab Injection [Stelara]

Intervention Description

Drug for Crohn's disease

Primary Outcome Measure Information:

Title

ITT, steroid free remission

Description

Defined as an improvement in one inflammatory marker (CRP or calprotectin)

Time Frame

week 12

Secondary Outcome Measure Information:

Title

Median calprotectin

Description

Reduction in median calprotectin compared to baseline between groups

Time Frame

week 12

Title

Intestinal bowel wall thickness

Description

Reduction in intestinal bowel wall thickness compared to baseline between groups for patients with increased bowel wall thickness measured on baseline US.

Time Frame

week 16

Title

UST trough level

Description

mean UST trough level between groups.

Time Frame

week 16

Title

CDAI between groups

Description

Median decline in CDAI between groups. Crohn's Disease Activity Index (CDAI) range between 0-800

Time Frame

week 16

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Informed consent. Age: 18- 65 years (inclusive). Established diagnosis of CD Starting Ustekinumab. Active disease defined as a CDAI >220, and have an objective measure of disease activity such as an elevated marker of inflammation (elevated CRP >5mg/L or 0.5 mg/dL or calprotectin >150 mcg/g). Patients must have previously received at least one dose of anti TNF at any time in the past. Stable medication at least 8 weeks. Inclusion criteria comments 1. Patients of any weight will be recruited and randomized to the study regardless of their BMI. Exclusion Criteria: Pregnancy or lactation Presence of malignancy Use of prednisone >20 mg /day Ongoing use of concurrent medications with a dose change in the previous 8 weeks with the exception of steroids (Patients receiving prednisone 20 mg or less may be enrolled by must be tapered by week 6). Treatment with an anti TNF in the last 4 weeks. Patients who will take oral iron oral supplements during the trial (see comment 1 below). Active infections, tuberculosis, positive stool test for Clostridium difficile toxin. Active perianal fistula (with discharge, or with an abscess during the past 3 months), rectovaginal fistula. Fever. Active extra intestinal disease (arthritis with joint swelling, concurrent liver disease). Patients with skin manifestations and arthralgia may be included. Smokers who smoke >5 more cigarettes a day (see comment 2 below). Renal failure. Uncontrolled diabetes that precludes the diet. Patients with isolated colonic disease distal to the transverse colon (see comment 3 below). Exclusion criteria comments Patients taking oral iron supplements may be enrolled if they discontinue the supplements prior to receiving UST, and are NOT ALLOWED to take oral iron supplements during the first 12 weeks of the trial as the diet reduces oral iron exposure to decrease siderophoric pathobionts (patients are allowed to receive intravenous iron or other oral vitamins during the trial). Patients who smoke >5 cigarettes per day may be enrolled if they stop smoking from the start of the trial (smoking negates the effect of the diet). Patients with isolated colonic disease distal to the transverse colon and no history of ileal disease will be excluded to make sure that IBDU is not recruited.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Michal Yaakov, Ph.D

Phone

972-35028878

michal.yaakov@walla.co.il

Facility Information:

Facility Name

Sheba Medical Center

City

Ramat Gan

ZIP/Postal Code

5262000

Country

Israel

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Uri Kopylev, MD

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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Stelara and Diet Trial for Crohn"s Disease

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