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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

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 Summary:

Overall study duration: 4 years Multi-center study: up to 50 centers

Number of subjects: 425 Duration of treatment for each subject: up to 104 weeks (2 years)

The primary endpoint is time to treatment failure.


Sponsor: University of North Carolina, Chapel Hill

Current Primary Outcome: Time to treatment failure [ Time Frame: Continuous from randomization through week 104 ]

Time from randomization to treatment failure defined as follows: Failure to achieve remission (SPCDAI < 15) by the week 26 visit; If study initiated on steroids, failure to complete steroid taper by week 16; SPCDAI ≥ 15 (active disease) at two or more consecutive visits beyond the week 26 visit; Hospitalization for active Irritable Bowel Disease or abdominal surgery after week 25; Use of oral prednisone or prednisolone, enteral release budesonide, or intravenous (IV) methylprednisolone for over 10 weeks cumulatively, beyond week 16. (Not inclusive of steroids used as premed for anti-TNF administration or steroids used for conditions other than CD); or discontinuation of anti-TNF or study drug for lack of effectiveness or toxicity.


Original Primary Outcome: Time to treatment failure [ Time Frame: Continuous from randomization through week 104 ]

Time from randomization to treatment failure defined as follows: Failure to achieve remission (SPCDAI < 15) at or just prior to week 26 visit; If study initiated on steroids, failure to complete steroid taper by week 16; SPCDAI ≥ 15 (active disease) at two or more consecutive visits beyond week 25; Hospitalization for active Irritable Bowel Disease or abdominal surgery after week 25; Use of oral prednisone or prednisolone, enteral release budesonide, or intravenous (IV) methylprednisolone for over 10 weeks cumulatively, beyond week 16. (Not inclusive of steroids used as premed for anti-TNF administration or steroids used for conditions other than CD); or discontinuation of anti-TNF or study drug for lack of effectiveness or toxicity.


Current Secondary Outcome:

  • Mean PROMIS (Patient Reported Outcome Measurement and Information System) Pain Interference T score by treatment arm [ Time Frame: Week 52 and 104 from randomization ]
    T scores are a continuous variable. The mean in the general population is 50 (SD=10). Scores above 50 represent higher than average pain interference and scores below 50 represent lower than average pain interference. We will compare the mean of PROMIS Pain Interference T scores at week 52 and week 104 between the treatment groups. Minimal important differences (MIDs) for many PROMIS domains are in the range of 2 to 6.
  • Mean PROMIS (Patient Reported Outcome Measurement and Information System) Fatigue T score by treatment arm [ Time Frame: Week 52 and 104 from randomization ]
    T scores are a continuous variable. The mean in the general population is 50 (SD=10). Scores above 50 represent higher than average fatigue and scores below 50 represent lower than average fatigue. We will compare the mean of PROMIS Fatigue T scores at week 52 and week 104 between the treatment groups. Minimal important differences (MIDs) for many PROMIS domains are in the range of 2 to 6.
  • Proportion of patients with positive anti-TNF antibody status [ Time Frame: Between week 91 and week 104 from randomization ]
    Proportion of patients with positive anti-TNF antibody status will be compared between the two treatment groups using the chi-squared test. The year two sample will be collected at a single time point between week 91 and week 104 from randomization. if a sample is not collected in the second year, the sample collected in the first year will be used (week 14).


Original Secondary Outcome:

  • Mean PROMIS (Patient Reported Outcome Measurement and Information System) Pain Interference T score by treatment arm [ Time Frame: Week 52 and 104 from randomization ]
    T scores are a continuous variable. The mean in the general population is 50 (SD=10). Scores above 50 represent higher than average pain interference and scores below 50 represent lower than average pain interference. We will compare the mean of PROMIS Pain Interference T scores at week 52 and week 104 between the treatment groups. Minimal important differences (MIDs) for many PROMIS domains are in the range of 2 to 6.
  • Mean PROMIS (Patient Reported Outcome Measurement and Information System) Fatigue T score by treatment arm [ Time Frame: Week 52 and 104 from randomization ]
    T scores are a continuous variable. The mean in the general population is 50 (SD=10). Scores above 50 represent higher than average fatigue and scores below 50 represent lower than average fatigue. We will compare the mean of PROMIS Fatigue T scores at week 52 and week 104 between the treatment groups. Minimal important differences (MIDs) for many PROMIS domains are in the range of 2 to 6.
  • Mean anti-TNF trough levels by treatment arm [ Time Frame: Between week 91 and week 104 from randomization ]
    Mean anti-TNF trough levels will be compared between the two treatment groups using Wilcoxon rank-sum test. The year two sample will be collected at a single time point between week 91 and week 104 from randomization.
  • Proportion of patients with positive anti-TNF antibody status [ Time Frame: Between week 91 and week 104 from randomization ]
    Proportion of patients with positive anti-TNF antibody status will be compared between the two treatment groups using the chi-squared test. The year two sample will be collected at a single time point between week 91 and week 104 from randomization.


Information By: University of North Carolina, Chapel Hill

Dates:
Date Received: April 27, 2016
Date Started: October 2016
Date Completion: December 2020
Last Updated: December 2, 2016
Last Verified: December 2016