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

Primary Purpose

Crohn's Disease

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Naltrexone
Placebo, sugar pill
Sponsored by
Milton S. Hershey Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Crohn's Disease focused on measuring children, pediatric, Crohn's Disease, naltrexone, LDN, IBD, Inflammatory bowel disease

Eligibility Criteria

6 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Penn State University hershey Medical center

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Sugar pill

Naltrexone

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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).
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.

Full Information

First Posted
July 14, 2008
Last Updated
September 4, 2018
Sponsor
Milton S. Hershey Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT00715117
Brief Title
The Efficacy of Low Dose Naltrexone Therapy in Children With Crohn's Disease
Acronym
LDN-Ped
Official Title
The Efficacy of Low Dose Naltrexone Therapy in Children With Crohn's Disease
Study Type
Interventional

2. Study Status

Record Verification Date
May 2013
Overall Recruitment Status
Completed
Study Start Date
July 2008 (undefined)
Primary Completion Date
May 2010 (Actual)
Study Completion Date
August 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Milton S. Hershey Medical Center

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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: 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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Crohn's Disease
Keywords
children, pediatric, Crohn's Disease, naltrexone, LDN, IBD, Inflammatory bowel disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sugar pill
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Naltrexone
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
Naltrexone
Other Intervention Name(s)
Revia, Vivitrol
Intervention Description
Naltrexone 0.1 mg/kg (not to exceed 4.5mg) once a day orally for 16 weeks
Intervention Type
Other
Intervention Name(s)
Placebo, sugar pill
Other Intervention Name(s)
sugar pill
Intervention Description
Placebo -Sugar pill or liquid identical to active drug in appearance and taste given by mouth at bedtime once daily
Primary Outcome Measure Information:
Title
Number of Patients Reporting Side Effects
Description
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.
Time Frame
8 weeks or 16 weeks
Secondary Outcome Measure Information:
Title
Pediatric Crohn's Disease Activity Index Score (PCDAI)
Description
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).
Time Frame
Pretreatment and 8 weeks
Title
Change in Quality of Life Scores From Baseline to After 8 Weeks of Naltrexone Therapy
Description
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.
Time Frame
16 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jill P Smith, MD
Organizational Affiliation
Pennsylvania State University College of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Penn State University hershey Medical center
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
17222320
Citation
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.
Results Reference
background
PubMed Identifier
21380937
Citation
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.
Results Reference
background
PubMed Identifier
23188075
Citation
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.
Results Reference
result
Links:
URL
http://www.hmc.psu.edu/clinicaltrials/studies/gi/index.htm
Description
Penn State College of Medicine- Clinical Trials Office Site

Learn more about this trial

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

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