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
  Purpose

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.

Condition Intervention Phase
Crohn's Disease
Drug: Naltrexone
Other: Placebo, sugar pill
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Efficacy of Low Dose Naltrexone Therapy in Children With Crohn's Disease

Resource links provided by NLM:


Further study details as provided by Penn State University:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 14
Study Start Date: July 2008
Study Completion Date: August 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
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.
Drug: Naltrexone
Naltrexone 0.1 mg/kg (not to exceed 4.5mg) once a day orally for 16 weeks
Other Name: Revia, Vivitrol

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

Ages Eligible for Study:   6 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00715117

Locations
United States, Pennsylvania
Penn State University hershey Medical center
Hershey, Pennsylvania, United States, 17033
Sponsors and Collaborators
Penn State University
Investigators
Principal Investigator: Jill P Smith, MD Pennsylvania State University College of Medicine
  More Information

Additional Information:
Publications:
Responsible Party: Jill P. Smith, Professor of Medicine, Penn State University
ClinicalTrials.gov Identifier: NCT00715117     History of Changes
Other Study ID Numbers: PSU-IRB-27793
Study First Received: July 14, 2008
Results First Received: August 4, 2011
Last Updated: May 29, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Penn State University:
children
pediatric
Crohn's Disease
naltrexone
LDN
IBD
Inflammatory bowel disease

Additional relevant MeSH terms:
Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Naltrexone
Narcotic Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 22, 2014