Clinical trial NCT02772965: Low Dose Oral Methotrexate in Pediatric Crohn's Disease Patients Initiating Anti-Tumor Necrosis Factor (Anti-TNF) Therapy
Official title: A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Pragmatic Clinical Trial To Evaluate The Effectiveness Of Low Dose Oral Methotrexate In Patients With Pediatric Crohn's Disease Initiating Anti-TNF Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pediatric Crohn's Disease
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Patient-Centered Outcomes Research Institute
name: ImproveCareNow (ICN)
name: The Leona M. and Harry B. Helmsley Charitable Trust
name: Children's Hospital Medical Center, Cincinnati
name: Grifols Diagnostics Solutions, Inc
name: National Institutes of Health (NIH)
name: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
First posted: 2016-05-16
Enrollment: 306
Sex: ALL
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether adding low dose methotrexate to anti -TNF therapy is more effective than treatment with anti-TNF therapy alone in inducing and maintaining steroid-free remission for children with Crohn's Disease.

Detailed description: Overall study duration: 6 years Multi-center study: up to 42 centers

Number of subjects: 425 Duration of treatment for each subject: up to 156 weeks (3 years)

The primary endpoint is percent of patients who experienced treatment failure over time.

Eligibility criteria: Inclusion Criteria:

* Pediatric Crohn's Disease (PCD) patients, \< 21 years of age, ≥20 kg, initiating anti-TNF therapy with infliximab or adalimumab (including biosimilars).
* Diagnosis of Crohn's Disease (CD) established confirmed by the treating clinician, and established by standard clinical criteria (radiography, endoscopy, histology).
* Ability to provide parental permission and child assent (where applicable), or adult consent for patients ages 18-20.

Exclusion Criteria:

* Prior use of anti-TNF or other biological therapy for CD
* Lack of stable home address that study medications can be mailed to
* Anticipated short length of follow up at study center (plans for family to move, transition to adult GI (gastrointestinal) provider, etc.). Patients expected to leave practice \< 12 months from enrollment should not be enrolled.
* Concurrent pelvic or abdominal abscess. A recent history of abdominal or pelvic abscess, which is controlled, does not exclude the subject.
* Prior intra-abdominal surgery without a clinically significant relapse (i.e. patients starting on anti-TNF for post-op prophylaxis or for endoscopic recurrence only should not be included)
* Receipt of a live virus vaccine within the last 30 days
* Pregnancy, planning to become pregnant, or high risk of pregnancy as determined by the local investigator
* Breastfeeding
* Refusal to stay abstinent or utilize 2 forms of birth control while on study medication (for female patients)
* BMI \> 98% for gender and age
* Known previous or concurrent malignancy (other than that considered surgically cured, with no evidence for recurrence for 5 years). A recent history of basal cell or squamous cell carcinoma, which is considered surgically cured, does not exclude the subject.Those with a recent history of colonic adenoma or dysplastic lesions should be excluded.
* Known high alcohol consumption (more than seven drinks per week)
* Patients with serum albumin \< 2.5 g/dl
* Patients with white blood cell count (WBC) \< 3.0 x109th/L
* Patients with platelet count \< 100 x109th/L
* Patients with initial elevation of liver enzymes (AST or ALT) \> 1.5 times above normal limit
* Patients with known active infection with Clostridium difficile (C. difficile) (untreated infection based on clinician assessment does not apply to colonization or infection controlled with current or prior treatment.)
* Patients with pre-existing hepatic disease
* Patients with pre-existing renal dysfunction (creatinine \> 0.8 for children age\<10, creatinine \> 1.2 mg/dl for children age 10-18, and creatinine \> 1.5 mg/dl for adults age 18 years and older).
* Patients with a pre-existing chronic lung disease other than well controlled asthma
* Current treatment with one of the following drugs: Probenecid (Probalan), Acitretin (Soriatane), Streptozocin (Zanosar), Azathioprine (Imuran, Azasan), 6-mercaptopurine (Purinethol, Purixan)
* Other concerns about the patient/family's ability to participate in the study

Primary outcomes:
measure: Percent of Participants Experiencing Treatment Failure
timeFrame: From randomization until treatment failure, assessed up to 3 years.
Secondary outcomes:
measure: Mean Patient Reported Outcome Measurement and Information System (PROMIS ) Pain Interference T-score-52 Weeks
timeFrame: Weeks 52 from randomization
measure: Mean Patient Reported Outcome Measurement and Information System (PROMIS ) Pain Interference T-score-week 104
timeFrame: 104 weeks from randomization
measure: Mean PROMIS (Patient Reported Outcome Measurement and Information System) Fatigue T Score-week 52
timeFrame: Week 52 from randomization
measure: Mean PROMIS (Patient Reported Outcome Measurement and Information System) Fatigue T Score-week 104
timeFrame: 104 weeks from randomization
measure: Percent of Patients With Positive Anti-TNF Antibody
timeFrame: Between 6 months and 2 years from randomization
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Children's of Alabama
state: Alabama
city: Alto
country: United States
facility: Stanford Children's Health
state: California
city: New Haven
country: United States
facility: Yale-New Haven Children's Hospital
state: Connecticut
city: Wilmington
country: United States
facility: Nemours Children's Health System - Wilmington
state: Delaware
city: Jacksonville
country: United States
facility: Nemours Children's Health System - Jacksonville
state: Florida
city: Miami
country: United States
facility: Nicklaus Children's Hospital
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Health System - Orlando
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta at Egleston/Emory University
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Children's Hospital
state: Iowa
city: Boston
country: United States
facility: MassGeneral Hospital for Children
state: Massachusetts
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan | CS Mott Children's Hospital
state: Michigan
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Cardinal Glennon Children's Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis Children's Hospital | Washington University
state: Missouri
city: Omaha
country: United States
facility: Children's Hospital and Medical Center Omaha
state: Nebraska
city: New York
country: United States
facility: Mount Sinai Kravis Children's Hospital
state: New York
city: Syracuse
country: United States
facility: Upstate Golisano Children's Hospital
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Levine Children's Hospital
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Rainbow Babies & Children's Hospital
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Dayton
country: United States
facility: Dayton Children's Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Medical Center
state: Oklahoma
city: Nashville
country: United States
facility: Monroe Carell Jr. Children's Hospital at Vanderbilt
state: Tennessee
city: Burlington
country: United States
facility: The University of Vermont Children's Hospital
state: Vermont
city: Fairfax
country: United States
facility: Pediatric Specialists of Virginia
state: Virginia
city: Norfolk
country: United States
facility: Children's Hospital of The King's Daughters
state: Virginia
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Michael D Kappelman, MD
role: STUDY_DIRECTOR
References: