Low Dose Oral Methotrexate in Pediatric Crohn's Disease Patients Initiating Anti-Tumor Necrosis Factor (Anti-TNF) Therapy

Purpose

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.

Condition

  • Pediatric Crohn's Disease

Eligibility

Eligible Ages
Under 20 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Triple (Participant, Care Provider, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Methotrexate
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
  • Drug: Methotrexate
    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.
    Other names:
    • Methotrexate Sodium
Placebo Comparator
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
  • Other: Sugar pill (placebo)
    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.

Recruiting Locations

Monroe Carell Jr. Children's Hospital at Vanderbilt
Nashville, Tennessee 37232
Contact:
Chelsea Campbell
615-875-6039
chelsea.n.campbell@vumc.org

More Details

Status
Recruiting
Sponsor
University of North Carolina, Chapel Hill

Study Contact

Michael D Kappelman, MD
(919) 843-5908
michael_kappelman@med.unc.edu

Detailed Description

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.