Clinical trial NCT00715117: The Efficacy of Low Dose Naltrexone Therapy in Children With Crohn's Disease
Official title: The Efficacy of Low Dose Naltrexone Therapy in Children With Crohn's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Crohn's Disease
Keywords: children
pediatric
Crohn's Disease
naltrexone
LDN
IBD
Inflammatory bowel disease
Lead sponsor: Milton S. Hershey Medical Center
Sponsor class: OTHER
First posted: 2008-07-15
Enrollment: 14
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: It is hypothesized that oral naltrexone will improve inflammation of the bowel by increasing endogenous enkephalin levels in subjects with active Crohn's disease. This is especially important in children who often are suffering from nutritional deprivation which retards their growth.

The key objectives are to:

1. Evaluate the effects of low dose naltrexone in children with Crohn's Disease by using the Pediatric Crohn's Disease Activity Index (PCDAI), plasma inflammatory markers, weight, and pediatric quality of life survey.
2. To determine the safety and toxicity of low dose naltrexone in pediatric subjects with active Crohn's Disease.
3. Assess the potential mechanism by which naltrexone exerts its action by measuring plasma opioid (enkephalin and endorphin levels) and proinflammatory cytokines.

Detailed description: The present proposal is designed as double-blinded placebo controlled study involving 30 children between 6-17 years of age with active Crohn's disease. Children will be treated with either naltrexone or placebo for the first 8 weeks then all subjects will receive active naltrexone drug the last 8 weeks. A one month follow-up appointment will be scheduled 4-weeks after completion of the active drug for safety and to assess Crohn's activity. Low dose naltrexone (LDN) will be dispensed in either capsules at a dose of 4.5 mg for those ages 10 years or older and in liquid form at 0.1 mg/kg for those under age of 10 or less than 45 kg. Half of the subjects in the first 8 weeks will be randomized to placebo which will be either capsules filled with avicel (see section 6.0) or diluent (flavored water) if in liquid form. Children are eligible who are not of child-bearing potential or are using two means of effective birth control, have a Pediatric Crohn's Disease Activity Index (PCDAI) of at least 31 points, and have the confirmed diagnosis of Crohn's disease by either endoscopic or radiographic tests.

Eligibility criteria: Inclusion Criteria:

* All subjects must give written informed consent by parent or guardian
* Male or female subjects, \> 6 - 17 years
* Patients must have endoscopic or radiographic confirmed Crohn's Disease.
* Patients must have a Pediatric Crohn's Disease Activity Index (PCDAI) of at least 31.

Exclusion Criteria:

* Adolescent women of childbearing potential and / or sexually active unless surgically sterile or using adequate contraception (either IUD, oral or deport contraceptive, or barrier plus spermicide), and willing and able to continue contraception for 3 months after the completion of the study.
* Adolescent women who are pregnant or breastfeeding
* Subjects with an ostomy or ileocolic anastomosis from surgery as these operations interfere with the PCDAI assessment
* Subjects taking tacrolimus, cyclosporin, mycophenolate, or anti-TNF-α therapy must be discontinued 4 weeks prior to study initiation.
* Patients with abnormal liver function tests
* Prednisone greater than 10 mg or \> 0.2 mg/kg orally

Primary outcomes:
measure: Number of Patients Reporting Side Effects
timeFrame: 8 weeks or 16 weeks
Secondary outcomes:
measure: Pediatric Crohn's Disease Activity Index Score (PCDAI)
timeFrame: Pretreatment and 8 weeks
measure: Change in Quality of Life Scores From Baseline to After 8 Weeks of Naltrexone Therapy
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Hershey
country: United States
facility: Penn State University hershey Medical center
state: Pennsylvania
Study officials:
affiliation: Pennsylvania State University College of Medicine
name: Jill P Smith, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Smith JP, Stock H, Bingaman S, Mauger D, Rogosnitzky M, Zagon IS. Low-dose naltrexone therapy improves active Crohn's disease. Am J Gastroenterol. 2007 Apr;102(4):820-8. doi: 10.1111/j.1572-0241.2007.01045.x. Epub 2007 Jan 11.
citation: Smith JP, Bingaman SI, Ruggiero F, Mauger DT, Mukherjee A, McGovern CO, Zagon IS. Therapy with the opioid antagonist naltrexone promotes mucosal healing in active Crohn's disease: a randomized placebo-controlled trial. Dig Dis Sci. 2011 Jul;56(7):2088-97. doi: 10.1007/s10620-011-1653-7. Epub 2011 Mar 8.
citation: Smith JP, Field D, Bingaman SI, Evans R, Mauger DT. Safety and tolerability of low-dose naltrexone therapy in children with moderate to severe Crohn's disease: a pilot study. J Clin Gastroenterol. 2013 Apr;47(4):339-45. doi: 10.1097/MCG.0b013e3182702f2b.