Low Dose Oral Methotrexate in Pediatric Crohn's Disease Patients Initiating Anti-Tumor Necrosis Factor (Anti-TNF) Therapy
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.
- Pediatric Crohn's Disease
- Eligible Ages
- Under 20 Years
- Eligible Genders
- Accepts Healthy Volunteers
- 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.
- 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
- Phase 3
- Study Type
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Triple (Participant, Care Provider, Investigator)
|Methotrexate (10, 12.5, or 15 mg), once weekly. Weight-based dosing. Ondansetron (4 mg), twice weekly, 1 hour prior to methotrexate dose and the morning after methotrexate dose. Folic Acid (1 mg) daily||
Sugar pill (placebo)
|Placebo for methotrexate, once weekly. Placebo for ondansetron, twice weekly, 1 hour prior to methotrexate placebo dose and the morning after methotrexate placebo dose. Folic Acid (1 mg) daily||
- University of North Carolina, Chapel Hill
Study ContactMichael D Kappelman, MD
Overall study duration: 4 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 time to treatment failure.