MILESTONE-CD -A Prospective Multiomic Inception Real -Life Study To Evaluate Predictors of Disease Outcomes & respoNse to Biologic Treatment in Crohn's Disease (MILESTONE-CD)

Crohn's' disease (CD) is a lifelong-chronic inflammatory condition of the digestive tract. CD frequently manifests during the 2nd or 3rd decade; prolonged disease duration frequently results in major structural complications such as strictures and fistulae, leading to surgery for control of complications in at least 30% of the patients. The course of disease is extremely diverse, ranging from a very mild disease to a devastating and incapacitating course. The burden of inflammatory bowel disease is growing each disease, reaching 400 billion USD for lifetime in US. In Israel, there are currently over 50000 IBD patients, with one of the highest incidences in the word, multiple treatment modalities and medications are available for Crohn's disease, however the efficacy is limited and the costs- very high. Furthermore, long-term exposure to some of the therapeutic agents poses an increased risk of infections and cancer.

Some of the major challenges in IBD include prediction of disease course (some patients will require early and aggressive treatment while others may just need observation and follow-up), and treatment personalization (right drug for the right patient at the right time). Unfortunately, individualized predictors of disease course and response to treatment are currently very limited. Some clues can be derived from imaging and endoscopy data, transcriptomics, genomic and microbiome, however those are still very premature and impractical. Moreover, large-scale studies with sophisticated predictive models that incorporate multilayered and multilayered clinical and omic data are severely lacking.

Study Overview

• Status: Active, not recruiting
• Conditions: Crohn Disease of Intestine
• Intervention / Treatment: Diagnostic test: combination of diagnostic tests

Detailed Description

Goal:

Create comprehensive patient-multiomic profile (PRO-Visualosome-microbiome-transcriptome-pharmacokineticome) to develop algorithm-based personalized IBD therapy

Design Prospective observational cohort study.

Study aim To detect predictors of response to biologics using a layered multiomic approach

Cohort size Up to 140 patients in 2 years

Study duration -Patients will be followed up to 2 years (possible extension) or until treatment discontinuation or intestinal surgery

Study procedures All study procedures will be performed for the purpose of the study

Baseline

Disease activity using Harvey Bradshaw score at all timepoints and visits

• baseline PROS -PROMIS10/SIBDQ/IBD control/PRO2 using DATOS app
• colonoscopy with Intestinal biopsies
• Blood for transcriptomics
• Blood/serum for serum and cellular markers
• Stool for microbiome/metabolomics (if colonoscopy done- a rectal swab during colonoscopy will be performed)
• Pillcam CD following patency capsule - if failed patients still will be included and continue follow- up without capsule endoscopy
• MRE
• IUS
• Fecal calprotectin home kit with CALPROSMART
• Basic chemistry
• Joint US (if joint symptoms) Repeated assessment -every month
• PROMIS10/SIBDQ/IBD control/-via DATOS app (during the first 14-16 weeks- PRO2 will be evaluated weekly) Continuous monitoring (mobile device via DATOS app)

First follow-up visit (12-14 weeks)

• Calprotectin
• Microbiome
• Blood for transcriptomics
• Blood/serum for serum and cellular markers, drug levels, CRP

Every 3 months

- Home calprotectin (Calprosmart) +microbiome

Every 6 months

• Clinic visit
• Pillcam CD
• IUS
• Blood for transcriptomics
• Blood/serum for serum and cellular markers, drug levels, CRP
• Calprotectin (home +ELISA) + microbiome

Upon failure (need to switch medication -defined by treating physician) or end of study

• Clinic visit
• Calprotectin *Home +ELISA)
• Microbiome
• Serum for transriptomics, metabolomics
• Blood/serum for serum and cellular markers, drug levels, CRP
• Repeat Pillcam CD (if not done within 6 months)
• Repeat IUS +thermal imaging (if not done within 6 months)

• MRE

  • Drug levels will be done at every infusion for IV drugs and every 6 months for SC biologics and at the end of induction (week 8-16)

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Ramat Gan, Israel
    • Sheba Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Crohn's disease
• Start of first-line biological therapy

Exclusion Criteria:

• Previous biologic therapy
• Previous surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
failure of first biologic	cessation or switch of first biologic as per decision of the treating physician (documentation of change of therapy from the first biologic for any reason)	2 years

Collaborators and Investigators

• Sponsor: Sheba Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2020
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): November 1, 2024

Study Registration Dates

• First Submitted: October 26, 2020
• First Submitted That Met QC Criteria: October 31, 2020
• First Posted (Actual): November 3, 2020

Study Record Updates

• Last Update Posted (Estimated): December 7, 2023
• Last Update Submitted That Met QC Criteria: December 6, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: SHEBA-20-7346-UK-CTIL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No