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

Sponsor

Sheba Medical Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT04612621

Collaborator

(none)

149

Enrollment

Location

Anticipated Duration (Months)

3.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Crohn Disease of Intestine	Diagnostic Test: combination of diagnostic tests	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

149 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

All enrolled patients will undergo similar interventionsAll enrolled patients will undergo similar interventions

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

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

Actual Study Start Date :

Nov 1, 2020

Anticipated Primary Completion Date :

Nov 1, 2024

Anticipated Study Completion Date :

Nov 1, 2024

Outcome Measures

Primary Outcome Measures

failure of first biologic [2 years]
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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Crohn's disease
Start of first-line biological therapy

Exclusion Criteria:

Previous biologic therapy
Previous surgery

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sheba Medical Center	Ramat Gan		Israel

Sponsors and Collaborators

Sheba Medical Center

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Sheba Medical Center

ClinicalTrials.gov Identifier:

NCT04612621

Other Study ID Numbers:

SHEBA-20-7346-UK-CTIL

First Posted:

Nov 3, 2020

Last Update Posted:

May 10, 2022

Last Verified:

May 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Crohn Disease

Study Results

No Results Posted as of May 10, 2022