Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Precision Crohn's Disease Management Utilizing Predictive Protein Panels (ENvISION) (ENvISION)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04131504
Recruitment Status : Recruiting
First Posted : October 18, 2019
Last Update Posted : November 7, 2019
Sponsor:
Collaborator:
The Leona M. and Harry B. Helmsley Charitable Trust
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati

Brief Summary:

Crohn's disease and ulcerative colitis affect about 1.6 to 3 million people in the United States with many of those being young children and adolescents. Physicians need better ways to inform decisions on therapy selection and recognize ongoing intestinal injury while on treatment.

The main reason for this research study is to see if a blood test or stool test, which measures specific proteins, taken just before starting a new treatment for Crohn's disease can predict a patient's ability to achieve complete intestinal healing. The investigators also want to see if the intensity of gut inflammation can be detected by measuring a separate set of proteins in the blood.


Condition or disease Intervention/treatment
Crohn's Disease IBD Drug: Infliximab Drug: Adalimumab

Detailed Description:

Despite the heterogeneity of CD phenotypes and a potentially aggressive course of inadequately treated CD, treatment selection for newly diagnosed patients is currently based on clinical factors which do not define CD sub-types. Now, with additional biologic therapies for CD, there is a critical need for individual biochemical analysis both pre-treatment, and following induction to assess the probability of durable remission. These data will inform decisions on continued dosing of the current biologic, or whether addition of combination therapy or switching to a therapy with an alternative mechanism of action will be more beneficial.

The Food & Drug Administration (FDA) defines a companion diagnostic as a device that can identify patients most likely to benefit from a therapy or a device to monitor response with the purpose to adjust the treatment to achieve improved effectiveness.Our global aim is to develop a companion diagnostic (peripheral blood panel) that accurately predicts the probability of deep remission (clinical remission with MH) to anti-TNF and a protein (blood) biomarker panel that reproducibly distinguishes endoscopic MH from active (ulcerated) intestinal inflammation in patients with CD.

The long-term strategy is to utilize the "low-risk" anti-TNF specific module (protein panel) to personalize CD therapy. With the addition of new biologics for CD, patients with a low-risk inflammatory profile would not only be expected to achieve MH but also predicted to respond to treatment escalation strategies while avoiding or stopping the drug (if drug exposure is optimized) sooner in patients in which the protein profile predicts a low probability of deep remission with anti-TNF. As additional therapies are approved for pediatric CD, the priority would be to avoid anti-TNF in patients with a "high-risk" protein profile and specifically select therapies that target the patient's individual inflammatory signature. Additionally, the investigators expect the protein profile of patients failing to achieve deep remission to provide further insight into molecular mechanisms contributing to the continued inflammation and thereby directing the next therapeutic option.

Layout table for study information
Study Type : Observational
Estimated Enrollment : 240 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Multi-Center, Prospective Study to Discover a Companion Diagnostic for Biologics Targeting TNF
Actual Study Start Date : October 16, 2019
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : August 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Crohn's Disease

Group/Cohort Intervention/treatment
Phase I - Cross-sectional Study (CD and Suspected IBD)
150 children and young adults who have been previously diagnosed with CD (anti-TNF naïve) or suspected of having IBD (based on clinical symptoms and laboratory testing) who are scheduled for a clinically-indicated colonoscopy are eligible to be enrolled in this cohort.
Phase I - Cross-sectional Study (healthy volunteers)
20 healthy controls will be enrolled at Cincinnati Children's Hospital only. Once demographics, past medical/surgical history and biospecimens (blood/stool) are collected, controls will complete participation.
Phase II - Longitudinal Study of Participants with CD
70 children and young adults who have been diagnosed with CD (anti-TNF naïve) and are scheduled to receive infliximab (or adalimumab) are eligible to be enrolled in this cohort.
Drug: Infliximab
No standard dosing regimen will be used and the dose will be determined by the treating physician
Other Name: Remicade

Drug: Adalimumab
No standard dosing regimen will be used and the dose will be determined by the treating physician
Other Name: Humira




Primary Outcome Measures :
  1. Sustained Deep Remission [ Time Frame: 1 year ]

    Sustained Deep Remission, defined as meeting all of the following at 1 year (check all that apply):

    • no wPCDAI score of ≥12.5 on two consecutive visits between week 30-52
    • wPCDAI at week 52 is <12.5
    • off prednisone between weeks 30-52
    • endoscopic remission (SES-CD<3)


Secondary Outcome Measures :
  1. End of Induction Outcomes: Clinical Response [ Time Frame: Week 16 ]
    Improvement of >17.5 points from baseline wPCDAI and/or Week 16 wPCDAI= <12.5 points

  2. End of Induction Outcomes: Clinical Remission [ Time Frame: Week 16 ]
    wPCDAI <12.5 at Week 16

  3. End of Induction Outcomes: Steroid Free Clinical Remission [ Time Frame: Week 16 ]
    wPCDAI <12.5 and off prednisone by Week 16

  4. End of Induction Outcomes: Fecal Biochemical Response [ Time Frame: Week 16 ]
    Fecal calprotectin improved >50% from baseline stool (+/- 30 days from Week 16)

  5. End of Induction Outcomes: Fecal Biochemical Remission [ Time Frame: Week 16 ]
    Fecal calprotectin <250µg/g at Week 16 (+/- 30 days)

  6. End of Induction Outcomes: Blood CRP Biochemical Remission [ Time Frame: Week 16 ]
    CRP <0.5 mg/dL at Week 16

  7. End of Induction Outcomes: Blood CD64 Biochemical Remission [ Time Frame: Week 16 ]
    nCD64 <4.5 at Week 16

  8. Week 52 Outcomes: Endoscopic Response [ Time Frame: 1 year ]
    50% reduction in SES-CD score from baseline SES-CD (if performed)

  9. Week 52 Outcomes: Endoscopic Remission [ Time Frame: 1 year ]
    SES-CD <3

  10. Week 52 Outcomes: Minimal Endoscopic Activity [ Time Frame: 1 year ]
    SES-CD <6 with no individual SES-CD subscore >1

  11. Week 52 Outcomes: Complete Intestinal Healing [ Time Frame: 1 year ]
    SES-CD = 0

  12. Week 52 Outcomes: Sustained, Steroid-free Clinical Remission [ Time Frame: 1 year ]
    wPCDAI <12.5 for all visits from weeks 30-52, off prednisone

  13. Week 52 Outcomes: Clinical Remission [ Time Frame: 1 year ]
    wPCDAI <12.5 and off prednisone at last study visit

  14. Week 52 Outcomes: Clinical Remission and Endoscopic Response [ Time Frame: 1 year ]
    wPCDAI <12.5 at week 52 and SES-CD>50% reduction from baseline

  15. Week 52 Outcomes: Clinical Remission and Minimal Endoscopic Activity [ Time Frame: 1 year ]
    wPCDAI <12.5 at week 52 and SES-CD<6 with no individual SES-CD subscore >1

  16. Week 52 Outcomes: Treatment Response [ Time Frame: 1 year ]
    continues on anti-TNF without surgery, hospitalization and off prednisone by week 16

  17. Week 52 Outcomes: Transmural ileal healing [ Time Frame: 1 year ]
    ileum subscore stage 0 (score = 0) or stage 1 (score 1-3)

  18. Week 52 Outcomes: Transmural colonic healing [ Time Frame: 1 year ]
    all segments of colon subscore stage 0 (score=0) or stage 1 (score 1-3)

  19. Week 52 Outcomes: Total Bowel Transmural healing [ Time Frame: 1 year ]
    total ileum and colonic subscore is not greater than stage 1 on either individual score

  20. Week 52 Outcomes: Fecal Biochemical Remission [ Time Frame: 1 year ]
    fecal calprotectin <250 µg/g at week 52

  21. Week 52 Outcomes: Deep Fecal Biochemical Remission [ Time Frame: 1 year ]
    fecal calprotectin <150 µg/g at week 52

  22. Week 52 Outcomes: CRP Biochemical Remission [ Time Frame: 1 year ]
    CRP <0.5 mg/dL at week 52

  23. Week 52 Outcomes: CD64 Biochemical Remission [ Time Frame: 1 year ]
    nCD64 <4.5 at week 52

  24. Week 52 Outcomes: PGA Remission [ Time Frame: 1 year ]
    physician-rated PGA is quiescent and subject is off prednisone


Biospecimen Retention:   Samples With DNA
  • Blood specimens will be collected for biomarker discovery and validation
  • Stool specimens will be collected for microbial analysis and additional IBD-related stool biomarkers
  • OPTIONAL: Four additional research-only intestinal pinch biopsies at the time of a clinically indicated or research-only colonoscopy


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   1 Year to 22 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

Potential IBD participants will be recruited through the Division of Gastroenterology at each participating site.

Healthy volunteers will be recruited from through direct advertising methods approved by the IRB and formal local databases intended for recruitment.

Criteria

Phase I - Cross-sectional Study (CD and Suspected IBD)

Inclusion Criteria:

  1. Age criteria: > 1 year to < 22 years of age
  2. Diagnosis of Crohn's disease, anti-TNF naïve, and colonoscopy scheduled OR
  3. Clinical suspicion for IBD (treatment naïve) and colonoscopy scheduled
  4. Permission of parent/guardian and assent or consent of research participant

Exclusion Criteria:

  1. Any prior treatment with an anti-TNF, such as infliximab, adalimumab, certolizumab or golimumab
  2. Known diagnosis of ulcerative colitis (UC) or inflammatory bowel disease-unspecified (IBD-U)
  3. Active or prior evidence of internal (abdominal/pelvic) penetrating fistula(e)
  4. Active intra-abdominal abscess or perianal abscess
  5. Active Clostridium difficile infection or other known enteric infection in last 2 weeks
  6. Current ileostomy or colostomy, extensive small bowel resection, ileoanal pouch or short bowel syndrome
  7. History of autoimmune disease (including autoimmune hepatitis, primary sclerosing cholangitis, thyroiditis, psoriasis or juvenile idiopathic arthritis)
  8. Any condition that in the opinion of the PI will prevent the research participant from taking part in this study

Phase I - Cross-sectional Study (healthy volunteers)

Inclusion Criteria:

  1. Age criteria: > 1 year to < 22 years of age
  2. Any CCHMC patient
  3. Permission of parent/guardian and assent or consent of research participant

Exclusion Criteria:

  1. Known diagnosis of one or more of the following: irritable bowel syndrome, gastroesophageal reflux, constipation, BMI>95% for age, small intestinal bacterial overgrowth (SIBO) or history of intestinal polyps
  2. Received any antibiotic in the last 30 days or known viral or bacterial illness in the last 30 days
  3. Any NSAID use in the last 14 days
  4. History of an autoimmune disease (including diabetes, autoimmune hepatitis, primary sclerosing cholangitis, thyroiditis, psoriasis or juvenile idiopathic arthritis)
  5. Any condition that in the opinion of the PI will prevent the research participant from taking part in this study

Phase II - Longitudinal Study of Participants with CD

Inclusion Criteria:

  1. Age criteria: > 1 year to < 22 years of age
  2. Diagnosis of Crohn's disease with:

    1. Luminal inflammation (ulcerations in ileum and/or colon visible by ileocolonoscopy) and
    2. Endoscopic evidence of active Crohn's disease (up to 90 days prior to starting anti-TNF) OR if no colonoscopy within 90 days then fecal calprotectin ≥250 µg/g or fecal lactoferrin >10 µg/g (<90 days from starting anti-TNF)
  3. Anti-TNF naïve
  4. Starting infliximab or adalimumab (or either biosimilar)
  5. Permission of parent/guardian and assent or consent of research participant

Exclusion Criteria:

  1. Crohn's disease limited to esophagus, stomach, duodenum or jejunum
  2. Prior treatment with infliximab, adalimumab, certolizumab or golimumab
  3. Known diagnosis of Ulcerative colitis (UC) or inflammatory bowel disease-unspecified (IBD-U)
  4. Active or prior evidence of internal (abdominal/pelvic) penetrating fistula(e)
  5. Active intra-abdominal abscess or perianal abscess
  6. Active Clostridium difficile infection or other known enteric infection in last 2 weeks
  7. Current ileostomy or colostomy, extensive small bowel resection, ileoanal pouch or short bowel syndrome
  8. History of autoimmune disease (including autoimmune hepatitis, primary sclerosing cholangitis, thyroiditis, psoriasis or juvenile idiopathic arthritis)
  9. Contraindications to MRI scanning, such as metal implants/non-compatible medical devices or medical conditions
  10. Any condition that in the opinion of the PI will prevent the research participant from taking part in this study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04131504


Contacts
Layout table for location contacts
Contact: Phillip Minar, MD, MS 513-636-4415 phillip.minar@cchmc.org

Locations
Layout table for location information
United States, Connecticut
Connecticut Children's Medical Center Not yet recruiting
Hartford, Connecticut, United States, 06016
Contact: Dena Hopkins       DHopkins01@connecticutchildrens.org   
Contact: Miriam Lincoln       Mlincoln@connecticutchildrens.org   
Principal Investigator: Jeffrey Hyams, MD         
United States, Ohio
Cincinnati Children's Hospital Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Kimberly Jackson       kimberly.jackson@cchmc.org   
Principal Investigator: Phillip Minar, MD, MS         
Nationwide Children's Hospital Not yet recruiting
Columbus, Ohio, United States, 43205
Contact: Ling Fan       ling.fan@nationwidechildrens.org   
Contact: Lina Yossef-Salameh       Lina.Yossef-Salameh@nationwidechildrens.org   
Principal Investigator: Brendan M Boyle, MD, MPH         
United States, Wisconsin
Medical College of Wisconsin Not yet recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Adriane Mueller       admueller@mcw.edu   
Principal Investigator: Joshua D Noe, MD         
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
The Leona M. and Harry B. Helmsley Charitable Trust
Investigators
Layout table for investigator information
Principal Investigator: Phillip Minar, MD, MS Children's Hospital Medical Center, Cincinnati

Layout table for additonal information
Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT04131504    
Other Study ID Numbers: 2019-0730
First Posted: October 18, 2019    Key Record Dates
Last Update Posted: November 7, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Adalimumab
Infliximab
Anti-Inflammatory Agents
Antirheumatic Agents
Dermatologic Agents
Gastrointestinal Agents