Biomarkers of Anti-TNF Treatment in IBD

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by Erasmus Medical Center
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
J.C. Escher, M.D., Erasmus Medical Center
ClinicalTrials.gov Identifier:
NCT01971970
First received: October 24, 2013
Last updated: NA
Last verified: October 2013
History: No changes posted
  Purpose

Anti-TNF treatment (infliximab (IFX), adalimumab (ADA)) has become standard therapy for refractory pediatric and adult Crohn's disease (CD) patients, and is used for the induction (primary response) and maintenance of remission. When effective, clinical and endoscopic remission is reached within weeks. However, primary non-response is observed in 20% of pediatric patients, and in 40% of adult CD patients, suggesting a more robust acute response to anti-TNF therapy in children as compared to adults.During maintenance treatment, 60 - 80% of patients have secondary loss of response, necessitating dose adjustments to maintain clinical response. Anti-TNF treatment is also increasingly used in ulcerative colitis (UC), and has been shown to induce remission in active disease. For UC, the comparison between the efficacy in children versus adults is more difficult to report as studies in children are scarce. Anti-TNF treatment is associated with rare but potentially fatal side effects, infusion reactions, and is an expensive treatment. To avoid overtreatment it is necessary to early identify non-responders to treatment, and therefore it is important to develop predictive biomarkers of treatment response.


Condition Intervention
Inflammatory Bowel Diseases
Biological: Infliximab
Biological: Adalimumab

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Biomarkers Predicting the Effect of Anti-TNF Treatment in Pediatric and Adult Inflammatory Bowel Disease

Resource links provided by NLM:


Further study details as provided by Erasmus Medical Center:

Primary Outcome Measures:
  • Pre-treatment serum level of endogenous anti-TNF in relation to primary clinical response or non-response [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Pre-treatment RNA expression profiles in relation to primary clinical response or non-response [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

whole blood, gastrointestinal tract biopsies,buccal epithelium


Estimated Enrollment: 60
Study Start Date: October 2013
Estimated Study Completion Date: February 2017
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Pediatric IBD patients
Anti-TNF naive patients with either Crohn's disease or ulcerative colitis will be treated with either Infliximab or Adalimumab
Biological: Infliximab
Remission induction in anti-TNF naïve patients will be achieved by administration of 5 mg/kg IFX infusions at week 0, 2 and 6.
Other Name: Remicade
Biological: Adalimumab
ADA is administered as subcutaneous injections every other week.In children (age below 18 years), remission induction in anti-TNF naïve patients will be achieved by an initial loading dose of 80 mg, followed by 40 mg 2 weeks later. In adults, remission is induced by 160 mg at week 0, followed by 80 mg at week 2
Other Name: Humira
Adult IBD patients
Anti-TNF naive patients with either Crohn's disease or ulcerative colitis will be treated with either Infliximab or Adalimumab
Biological: Infliximab
Remission induction in anti-TNF naïve patients will be achieved by administration of 5 mg/kg IFX infusions at week 0, 2 and 6.
Other Name: Remicade
Biological: Adalimumab
ADA is administered as subcutaneous injections every other week.In children (age below 18 years), remission induction in anti-TNF naïve patients will be achieved by an initial loading dose of 80 mg, followed by 40 mg 2 weeks later. In adults, remission is induced by 160 mg at week 0, followed by 80 mg at week 2
Other Name: Humira

  Eligibility

Ages Eligible for Study:   6 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Pediatric and adult IBD patients from the Department of Pediatric Gastroenterology of Erasmus MC-Sophia Children's Hospital and from the Department of Gastroenterology of Erasmus MC respectively.

Criteria

Inclusion Criteria:

  • Anti-TNF naïve CD patients (≥ 6 years) who initiate anti-TNF treatment (IFX or ADA) because of active luminal disease, failing treatment with immunomodulators (azathioprine, 6-mercaptopurine, methotrexate) and corticosteroids.
  • Anti-TNF naïve UC patients (≥ 6 years) who initiate anti-TNF treatment (IFX or ADA) because of active disease despite corticosteroid treatment or because of failing of immunomodulator treatment.
  • Anti-TNF naïve CD or UC patients (≥ 6 years) who initiate anti-TNF treatment (IFX or ADA) because of intolerance to treatment with immunomodulators (azathioprine, 6-mercaptopurine, methotrexate) or corticosteroids.
  • Informed consent by patients and parents (when required).

Exclusion Criteria:

  • IBD patients who initiate IFX or ADA immediately after diagnosis.
  • Presence of severe perianal disease as primary indication to start anti-TNF treatment.
  • Age < 6 years when anti-TNF maintenance treatment is initiated.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01971970

Contacts
Contact: J C Escher, MD, PhD +31 10 7036049 ext 4 j.escher@erasmusmc.nl
Contact: C J van der Woude, MD, PhD +31 10 7033020 c.vanderwoude@erasmusmc.nl

Locations
Netherlands
Erasmus Medical Center Recruiting
Rotterdam, Netherlands, 3015 GJ
Principal Investigator: J C Escher, MD, PhD         
Principal Investigator: C J van der Woude, MD, PhD         
Sub-Investigator: D A Winter, MD, PhD student         
Sponsors and Collaborators
Erasmus Medical Center
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: J C Escher, MD, PhD Erasmus Medical Center - Sophia Children's Hospital
Principal Investigator: C J van der Woude, MD, PhD Erasmus Medical Center
  More Information

No publications provided

Responsible Party: J.C. Escher, M.D., Associate Professor, Erasmus Medical Center
ClinicalTrials.gov Identifier: NCT01971970     History of Changes
Other Study ID Numbers: NL-42736.078.13
Study First Received: October 24, 2013
Last Updated: October 24, 2013
Health Authority: Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by Erasmus Medical Center:
Inflammatory bowel disease
Pediatric
Adult
Biomarker
Anti-TNF response
Infliximab
Adalimumab

Additional relevant MeSH terms:
Intestinal Diseases
Inflammatory Bowel Diseases
Gastrointestinal Diseases
Digestive System Diseases
Gastroenteritis
Adalimumab
Infliximab
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antirheumatic Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Dermatologic Agents
Gastrointestinal Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 16, 2014