The Efficacy of Low Dose Naltrexone Therapy in Children With Crohn's Disease

Condition(s) targeted: Crohn's Disease

Intervention: Naltrexone (Drug); Placebo, sugar pill (Other)

Phase: Phase 2

Status: Completed

Sponsored by: Penn State University

Official(s) and/or principal investigator(s):
Jill P Smith, MD, Principal Investigator, Affiliation: Pennsylvania State University College of Medicine

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.

Official title: The Efficacy of Low Dose Naltrexone Therapy in Children With Crohn's Disease

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Number of Patients Reporting Side Effects

Secondary outcome:

Pediatric Crohn's Disease Activity Index Score (PCDAI)

Change in Quality of Life Scores From Baseline to After 8 Weeks of Naltrexone Therapy

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.

Minimum age: 6 Years. Maximum age: 17 Years. Gender(s): Both.

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

Penn State University hershey Medical center, Hershey, Pennsylvania 17033, United States

Penn State College of Medicine- Clinical Trials Office Site

Related publications:

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. Epub 2007 Jan 11.

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.

Starting date: July 2008
Last updated: May 29, 2013