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

• ClinicalTrials.gov Identifier: NCT00715117
• Recruitment Status: Completed
• First Posted: July 15, 2008
• Results First Posted: May 30, 2013
• Last Update Posted: September 6, 2018
• Sponsor: Milton S. Hershey Medical Center
• Information provided by (Responsible Party): Milton S. Hershey Medical Center

Tracking Information

• First Submitted Date: July 14, 2008
• First Posted Date: July 15, 2008
• Results First Submitted Date: August 4, 2011
• Results First Posted Date: May 30, 2013
• Last Update Posted Date: September 6, 2018
• Study Start Date: July 2008
• Actual Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 29, 2013)

Number of Patients Reporting Side Effects [ Time Frame: 8 weeks or 16 weeks ]

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.

• Original Primary Outcome Measures (submitted: July 14, 2008): Pediatric Crohn's Disease Activity Index Score [ Time Frame: 5 months ]

Current Secondary Outcome Measures (submitted: May 29, 2013)

• Pediatric Crohn's Disease Activity Index Score (PCDAI) [ Time Frame: Pretreatment and 8 weeks ]
  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 ]
  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.

• Original Secondary Outcome Measures (submitted: July 14, 2008): IMPACT III which measures quality of life [ Time Frame: 5 months ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Crohn's Disease

Intervention

• 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

Study Arms

• 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

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. doi: 10.1111/j.1572-0241.2007.01045.x. 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 18, 2011): 14
• Original Estimated Enrollment (submitted: July 14, 2008): 30
• Actual Study Completion Date: August 2010
• Actual Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Years to 17 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00715117
• Other Study ID Numbers: PSU-IRB-27793
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Milton S. Hershey Medical Center
• Original Responsible Party: Jill P. Smith, MD, Penn State University
• Current Study Sponsor: Milton S. Hershey Medical Center
• Original Study Sponsor: Penn State University
• Collaborators: Not Provided

Investigators

• Principal Investigator: Jill P Smith, MD; Pennsylvania State University College of Medicine

• PRS Account: Milton S. Hershey Medical Center
• Verification Date: May 2013