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

Study Overview
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Brief Summary
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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: 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. To determine the safety and toxicity of low dose naltrexone in pediatric subjects with active Crohn's Disease. Assess the potential mechanism by which naltrexone exerts its action by measuring plasma opioid (enkephalin and endorphin levels) and proinflammatory cytokines.

Detailed Description
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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.

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

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: Naltrexone
* Other: Placebo, sugar pill


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Sugar pill<br>Subjects will receive placebo for for the first 8 weeks administered orally one time daily. After 8 weeks placebo treated subjects are then crossed over to active drug naltrexone 0.1 mg/kg not to exceed 4.5 mg PO once daily for an additional 8 weeks. | Other: Placebo, sugar pill<br>* Placebo -Sugar pill or liquid identical to active drug in appearance and taste given by mouth at bedtime once daily<br>* Other names: sugar pill;|
| Experimental: Naltrexone<br>Naltrexone 0.1 mg/kg (not to exceed 4.5mg) once a day orally either in capsules or liquid blinded for 8 weeks followed by open-labeled naltrexone for an additional 8 weeks. Safety and toxicity will be compared to placebo. Also change in Crohn's activity index scores of naltrexone to placebo are compared. | Drug: Naltrexone<br>* Naltrexone 0.1 mg/kg (not to exceed 4.5mg) once a day orally for 16 weeks<br>* Other names: Revia, Vivitrol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Reporting Side Effects | Using adverse events and laboratory values Safety & toxicity were evaluated between those on placebo for 8 weeks and those on naltrexone for either 8 or 16 weeks. | 8 weeks or 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pediatric Crohn's Disease Activity Index Score (PCDAI) | Secondary outcome was efficacy on clinical activity. Mean pretreatment PCDAI scores in patients had moderate to severe disease activity at baseline were compared between those who received placebo for 8 weeks and those who received active experimental drug, naltrexone. The PCDAI score is a number unit that is calculated from symptoms scores by the subject over a 7-day period prior to the visit, laboratory values, height & weight, and physical exam findings. A score of 10 and under denotes remission. Mild disease (score of 11-30); moderate disease (score of 31-45), a severe disease (scores greater than 45. A decline of 10 points or more is considered response to therapy. The score can range from 0 to >60 Patient must have a PCDAI score of equal or greater than 30 to qualify for this study (i.e., moderate to severe disease). | Pretreatment and 8 weeks | 
| Change in Quality of Life Scores From Baseline to After 8 Weeks of Naltrexone Therapy | IMPACT III was a pediatric Crohn's specific quality of life survey used in this study. It examines five major categories influencing the quality of life in children with Crohn's disease including bowel symptoms, systemic symptoms, emotional well-being, social well-being, and body image perception. The IMPACT-III uses 5-point Likert scale ranging from 1 to 5 for all answers. The outcome score ranges from 35 to 175, with higher scores suggesting better quality of life. So an increase in score denotes improved Quality of life. | 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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children, pediatric, Crohn's Disease, naltrexone, LDN, IBD, Inflammatory bowel disease