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Clinical, Imaging, and Endoscopic Outcomes of Children Newly Diagnosed With Crohn's Disease (CAMEO)

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: NCT05781152
Recruitment Status : Recruiting
First Posted : March 23, 2023
Last Update Posted : April 16, 2024
Sponsor:
Collaborators:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Emory University
Children's Hospital Medical Center, Cincinnati
University of North Carolina, Chapel Hill
Information provided by (Responsible Party):
Connecticut Children's Medical Center

Brief Summary:
Crohn's disease (CD) is a condition that causes inflammation (swelling, redness) of the lining and wall of the small intestine, large intestine, or both. CD may be associated with abdominal cramps/pain, diarrhea, blood in the stool, weight loss, or delayed growth in children. While the exact cause of CD is not certain it is thought that the immune system located in the intestine reacts abnormally to the large number of bacteria contained there. The investigators think that diet, exposure to antibiotics early in life, and having a family history of CD puts people at increased risk for developing CD. In order to decrease the inflammation doctors use what is called biologic therapy with anti-TNF molecules that can be given through an intravenous or shots. TNF is a chemical made by white blood cells that is involved in inflammation. When this type of treatment is given early after diagnosis it is more effective than when it is given later. The investigators have learned that it is important to give the optimum (ideal) amount of this medicine guided by certain blood tests. The investigators also know that not everyone responds to this therapy but do not understand the reasons for this variability between people. The CAMEO study has been started to help understand what factors are important in determining whether a child with CD completely heals the inflammation after anti-TNF therapy. The investigators will do that by measuring certain markers of inflammation in the blood and stool and by looking at a person's genes (DNA) and how inflammation is controlled in the intestine. These inflammation tests will be done before, during, and after one year of anti-TNF therapy. The investigators will determine how much healing has taken place by comparing the results of the colonoscopy and a special type of MRI that are both done before anti-TNF and then again one year later. The goal in treating CD is to heal both the lining and the wall of the intestine. Children ages 6-17 years who are thought to have CD and are about to undergo their diagnostic colonoscopy are eligible to be enrolled. If they are found to indeed have CD and start an anti-TNF medicine within 6 months they can continue in the study. There are no increased risks of participating in this study beyond those normally associated with having CD and its treatment. By better understanding why the bowel does or does not heal, doctors will be better able to provide personalized care.

Condition or disease Intervention/treatment Phase
Crohn Disease Drug: Anti-TNF therapy Phase 4

Detailed Description:
Study Sites: Approximately 27 pediatric clinical centers in North America Study Period: Planned enrollment period - 3 years Planned duration of the study: 5 years Primary Study Objective: Identify clinical, radiologic, genomic, immune, microbial and transcriptomic factors associated with complete intestinal healing (CH) in the context of optimized anti-TNF therapy in children with newly diagnosed CD Secondary Study Objective: Identify clinical, radiologic, genomic, immune, microbial and transcriptomic factors associated with endoscopic healing only, transmural healing by MRE only, endoscopic response only, transmural response only, clinical remission, fecal calprotectin normalization, in the context of optimized anti-TNF therapy in children with newly diagnosed CD Study Design: Prospective multicenter open label single arm clinical trial with 2-phase enrollment Sample Size: Phase 1: 900; Phase 2: 550

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 900 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Clinical, Imaging, and Endoscopic Outcomes of Children Newly Diagnosed With Crohn's Disease
Actual Study Start Date : June 10, 2023
Estimated Primary Completion Date : July 1, 2028
Estimated Study Completion Date : July 1, 2029

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Anti-tumor necrosis factor (TNF)
Patients newly diagnosed with pediatric-onset Crohn's disease starting anti-TNF therapy within 6 months of diagnosis
Drug: Anti-TNF therapy
Use of anti-TNF therapy for children and adolescents with newly diagnosed Crohn's disease guided by a clinical decision support tool
Other Name: Remicade, Inflectra, Renflexis, Avsola, Humira, Amgevita, Hulio, Hadlima, Hyrimoz, Idacio




Primary Outcome Measures :
  1. Complete healing (CH) [ Time Frame: 52 weeks from anti-TNF start ]

    The achievement of complete healing (CH) 52 weeks after initiation of anti-TNF therapy guided by ROADMAB™ (therapeutic drug monitoring) as evidenced by a composite of all of the following four features below:

    1. Endoscopic healing (EH) determined by centrally read ileocolonoscopy (total SES-CD score <3)
    2. Transmural healing (TH) determined by centrally read MRE (no segmental MaRIAs score of ≥1)
    3. Corticosteroid free for a minimum of 4 weeks
    4. The absence of either intestinal resection or the addition of a nutritional, biological or small molecule therapeutic agent other than anti-TNF± concomitant IM


Secondary Outcome Measures :
  1. Endoscopic mucosal healing only [ Time Frame: 52 weeks ]
    Following approximately 52 weeks of anti-TNF therapy guided by the ROADMAB™ Clinical Decision Support Tool (CDST), with a minimum of 4 weeks of being corticosteroid free, and in the absence of either intestinal resection or the addition of a biological or small molecule therapeutic agent other than anti-TNF± concomitant IM: Endoscopic mucosal healing only (total Simple Endoscopic Score - Crohn's Disease (SES-CD) <3)

  2. Transmural healing only [ Time Frame: 52 weeks ]
    Following approximately 52 weeks of anti-TNF therapy guided by the ROADMAB™ Clinical Decision Support Tool (CDST), with a minimum of 4 weeks of being corticosteroid free, and in the absence of either intestinal resection or the addition of a biological or small molecule therapeutic agent other than anti-TNF± concomitant IM: Transmural healing only (no segmental simplified magnetic resonance index of activity (MaRIAs) score ≥1)

  3. Clinical remission [ Time Frame: 52 weeks ]
    Following approximately 52 weeks of anti-TNF therapy guided by the ROADMAB™ Clinical Decision Support Tool (CDST), with a minimum of 4 weeks of being corticosteroid free, and in the absence of either intestinal resection or the addition of a biological or small molecule therapeutic agent other than anti-TNF± concomitant IM: Clinical remission (weighted Pediatric Crohn's Disease Activity Index (wPCDAI) < 12.5)

  4. Fecal calprotectin [ Time Frame: 52 weeks ]
    Following approximately 52 weeks of anti-TNF therapy guided by the ROADMAB™ Clinical Decision Support Tool (CDST), with a minimum of 4 weeks of being corticosteroid free, and in the absence of either intestinal resection or the addition of a biological or small molecule therapeutic agent other than anti-TNF± concomitant IM: Fecal calprotectin <250 ug/g

  5. Endoscopic response [ Time Frame: 52 weeks ]
    Following approximately 52 weeks of anti-TNF therapy guided by the ROADMAB™ Clinical Decision Support Tool (CDST), with a minimum of 4 weeks of being corticosteroid free, and in the absence of either intestinal resection or the addition of a biological or small molecule therapeutic agent other than anti-TNF± concomitant IM: Endoscopic response: 50% reduction in SES-CD

  6. Transmural response [ Time Frame: 52 weeks ]
    Following approximately 52 weeks of anti-TNF therapy guided by the ROADMAB™ Clinical Decision Support Tool (CDST), with a minimum of 4 weeks of being corticosteroid free, and in the absence of either intestinal resection or the addition of a biological or small molecule therapeutic agent other than anti-TNF± concomitant IM: Transmural response: 50% reduction in MaRIAs



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.


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Ages Eligible for Study:   6 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Phase 1 Inclusion Criteria

  1. Age ≥ 6 years and < 18 years at enrollment
  2. Suspected diagnosis of CD
  3. Stool culture if performed that is negative for routine enteric pathogens (Salmonella, Shigella, Campylobacter, E. coli 0157:H7) and Clostridium difficile toxin in patients presenting with diarrhea. If history of C. difficile then a minimum of 6 weeks duration from treatment start and negative repeat stool for C. difficile toxin.
  4. Parent/guardian consent and patient assent
  5. Ability to remain in follow-up for up to 6 months of initial observation followed by a minimum of 52 weeks after possible start of anti-TNF therapy

Phase 1 Exclusion Criteria

  1. Diagnosis of CD following abdominal resectional surgery/appendectomy at initial presentation
  2. Investigator judgment that patient has high likelihood (>50%) of needing bowel resection within 3 months of diagnosis (i.e., presentation with perforation, bowel obstruction from stricture)
  3. Use of any oral CS for non-gastrointestinal indication within the four weeks prior to diagnostic assessment and biosampling (e.g., asthma)
  4. Use of any investigational drug within the past four weeks prior to diagnostic assessment and sampling
  5. Pregnancy
  6. Patients with poorly controlled medical conditions (e.g. diabetes, congestive heart failure)
  7. Previous treatment with immunomodulators or anti-TNF therapy for other medical conditions (e.g., juvenile idiopathic arthritis) at any time prior to enrollment
  8. Previous treatment with non-anti TNF biologics or small molecules for non-IBD indications in the past 6 months, with the exception of dupilumab (Dupixent) for asthma, eczema, or eosinophilic esophagitis
  9. Inability to have MRE because of claustrophobia or other reasons

Phase 2 Inclusion Criteria

  1. Met all eligibility criteria for Phase 1 and participated in Phase 1
  2. Diagnosed with macroscopic CD involving the terminal ileum and/or colon by endoscopic evaluation
  3. MRE imaging within 6 weeks of ileocolonoscopy and no more than 4 weeks after starting initial therapy (TT). A limited 'research protocol' MRE is acceptable in participants who have undergone a clinical CTE during their initial diagnostic evaluation; see Manual of Procedures for details.
  4. Received at least one of the following as initial therapy upon diagnosis:

    1. Corticosteroids
    2. Immunomodulator
    3. Defined nutritional therapy
    4. Anti-TNF (adalimumab or infliximab)
  5. Commenced adalimumab or infliximab anti-TNF therapy guided by ROADMAB™ CDST as first therapy or within 180 days of diagnosis (TD), with or without concomitant immunomodulator

6 a. Had ileal and rectal biopsies, OR b. Ileal biopsies are not obtained secondary to inflammatory or structural changes at the ileocecal valve or distal ileum that prevent ileal intubation. To be acceptable for Phase 2, the following additional criteria must be met: b1. Gross inflammation or obvious narrowing at the IC valve or distal ileum as documented by the video colonoscopy, AND b2. MRE documentation of TI inflammation with or without narrowing 7. Parent/guardian consent and patient assent 8. Ability to remain in follow-up for a minimum of 52 weeks after start of anti-TNF therapy

Phase 2 Exclusion Criteria

  1. Diagnosis of CD using video capsule endoscopy only with normal ileocolonoscopy and normal MRE
  2. Orofacial CD only
  3. Esophageal, gastric, duodenal, and/or jejunal CD only
  4. Severe complex fistulizing perianal disease +/- abscess, or perianal disease requiring surgical intervention or likely to require on-going surgical intervention possibly including diversion. The placement of a seton is not exclusionary. Incision and drainage of a perirectal abscess is also not exclusionary.
  5. Perianal CD only with no evidence of luminal disease
  6. Internal fistulizing disease at diagnosis
  7. Initial IBD treatment with non-anti-TNF biologic or small molecule therapy
  8. Received any anti-TNF agent other than adalimumab or infliximab
  9. Investigator judgment that patient unlikely to return for clinical, endoscopic or MRE follow-up
  10. Inability to have MRE because of claustrophobia or other reasons
  11. Video of baseline endoscopy not available for central reading
  12. Underwent bowel resection within 3 months of diagnosis (TD)

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): NCT05781152


Contacts
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Contact: Dena E Hopkins, MPH, CCRP 860-545-8125 CAMEO_CCC@connecticutchildrens.org
Contact: Jeffrey S Hyams, MD 860-545-9560 jhyams@connecticutchildrens.org

Locations
Show Show 26 study locations
Sponsors and Collaborators
Connecticut Children's Medical Center
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Emory University
Children's Hospital Medical Center, Cincinnati
University of North Carolina, Chapel Hill
Investigators
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Principal Investigator: Jeffrey S Hyams, MD Connecticut Children's Medical Center
Principal Investigator: Subra Kugathasan, MD Emory University
Principal Investigator: Lee Denson, MD Children's Hospital Medical Center, Cincinnati
  Study Documents (Full-Text)

Documents provided by Connecticut Children's Medical Center:
Informed Consent Form  [PDF] April 3, 2023

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Responsible Party: Connecticut Children's Medical Center
ClinicalTrials.gov Identifier: NCT05781152    
Other Study ID Numbers: 22-066
1U01DK134356-01 ( U.S. NIH Grant/Contract )
First Posted: March 23, 2023    Key Record Dates
Last Update Posted: April 16, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The final dataset will include de-identified demographic, clinical, genetic, serological, immune, microbiome, and gene expression data along with patient outcomes. The project will generate a bank of biological samples including serum, plasma, genomic DNA, ileal and colonic biopsy DNA & RNA, and stool. The investigators will use a data sharing agreement that provides for a commitment to using the data only for research purposes, a commitment to securing the data using appropriate computer technology, and a commitment to destroying or returning the data after analyses are completed. The data and access to the biospecimens for ancillary studies will be made available in a timely fashion following completion and publication of the primary outcome papers. The investigators will follow the prevailing standards and NIDDK Data Sharing Policy guidelines in documenting and depositing data sets. Quality-controlled raw data and processed data used in publications will be made available.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: 3 years after final outcome data collection
Access Criteria: The institutions and PIs will adhere to the NIH Grants Policy on Sharing of Unique Research Resources including the Sharing of Biomedical Research Resources: Guidelines for Recipients of NIH Grants and Contracts on Obtaining and Disseminating Biomedical Research Resources.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Connecticut Children's Medical Center:
crohn disease
children
pediatric
anti-TNF therapy
therapeutic drug monitoring
intestinal microbiome
inflammatory bowel disease
gene expression
genomic DNA
Additional relevant MeSH terms:
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Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Infliximab
Tumor Necrosis Factor Inhibitors
Anti-Inflammatory Agents
Dermatologic Agents
Gastrointestinal Agents
Antirheumatic Agents