The Efficacy of Low Dose Naltrexone Therapy in Children With Crohn's Disease (LDN-Ped)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Jill P. Smith, Penn State University
ClinicalTrials.gov Identifier:
NCT00715117
First received: July 14, 2008
Last updated: May 29, 2013
Last verified: May 2013

July 14, 2008
May 29, 2013
July 2008
May 2010   (final data collection date for primary outcome measure)
Number of Patients Reporting Side Effects [ Time Frame: 8 weeks or 16 weeks ] [ Designated as safety issue: Yes ]
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.
Pediatric Crohn's Disease Activity Index Score [ Time Frame: 5 months ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00715117 on ClinicalTrials.gov Archive Site
  • Pediatric Crohn's Disease Activity Index Score (PCDAI) [ Time Frame: Pretreatment and 8 weeks ] [ Designated as safety issue: Yes ]

    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).

  • Change in Quality of Life Scores From Baseline to After 8 Weeks of Naltrexone Therapy [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
    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.
IMPACT III which measures quality of life [ Time Frame: 5 months ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
The Efficacy of Low Dose Naltrexone Therapy in Children With Crohn's Disease
The Efficacy of Low Dose Naltrexone Therapy in Children With Crohn's Disease

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Crohn's Disease
  • Drug: Naltrexone
    Naltrexone 0.1 mg/kg (not to exceed 4.5mg) once a day orally for 16 weeks
    Other Name: Revia, Vivitrol
  • Other: Placebo, sugar pill
    Placebo -Sugar pill or liquid identical to active drug in appearance and taste given by mouth at bedtime once daily
    Other Name: sugar pill
  • Placebo Comparator: Sugar pill
    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.
    Intervention: Other: Placebo, sugar pill
  • Experimental: Naltrexone
    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.
    Intervention: Drug: Naltrexone

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
14
August 2010
May 2010   (final data collection date for primary outcome measure)

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
Both
6 Years to 17 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00715117
PSU-IRB-27793
Yes
Jill P. Smith, Penn State University
Penn State University
Not Provided
Principal Investigator: Jill P Smith, MD Pennsylvania State University College of Medicine
Penn State University
May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP