Low Dose Oral Methotrexate in Pediatric Crohn's Disease Patients Initiating Anti-Tumor Necrosis Factor (Anti-TNF) Therapy
Condition: Pediatric Crohn's Disease
MeSH terms: Crohn Disease
Intervention: Methotrexate; Sugar pill (placebo)
Intervention description: Oral methotrexate (MTX): The weekly dose will be 15 mg for children ≥ 40kg, 12.5 mg for children 30 to <40 kg, and 10 mg for children 20 to <30 kg.
A twice per week, 4mg dose of ondansetron will be provided as pre-treatment to prevent nausea (study provider may opt-out of this component based on clinical judgement).
A 1 mg dose of folic acid per day will be provided. This will help to reduce the risk of side effects in the MTX group.
Drug kits will contain a 3 month supply of each medication. Refills will be provided every 3 months until week 156 unless there is a failure to induce and maintain remission, development of unacceptable toxicity, pregnancy in a female participant, or failure of the participant to attend scheduled study visits.; Placebo for methotrexate: The weekly dose will mimic that of methotrexate.
Placebo for ondansetron: The weekly dose will mimic that of ondansetron (study provider may opt-out of this component based on clinical judgement).
A 1 mg dose of folic acid per day will be provided to maintain blinding.
Drug kits will contain a 3 month supply of each medication. Refills will be provided every 3 months until week 156 unless there is a failure to induce and maintain remission, development of unacceptable toxicity, pregnancy in a female participant, or failure of the participant to attend scheduled study visits.
Intervention MeSH terms: Methotrexate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 306.0
Sex: All
Maximum age: 20 Years
Healthy volunteers: No

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.
    

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