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

NCT00715117 | Completed Phase 2 Results DMC

• 1 other identifier: PSU-IRB-27793
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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

Conditions

Crohn's Disease

Keywords

children; pediatric; Crohn's Disease; naltrexone; LDN; IBD; Inflammatory bowel disease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Pediatric Crohn's Disease Activity Index Score (PCDAI)

  Pretreatment and 8 weeks

• Change in Quality of Life Scores From Baseline to After 8 Weeks of Naltrexone Therapy

  16 weeks

Study Arms (2)

Sugar pill

PLACEBO COMPARATOR

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

Naltrexone

EXPERIMENTAL

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

Interventions

Naltrexone DRUG

Naltrexone 0.1 mg/kg (not to exceed 4.5mg) once a day orally for 16 weeks

Also known as: Revia, Vivitrol

Naltrexone

Placebo, sugar pill OTHER

Placebo -Sugar pill or liquid identical to active drug in appearance and taste given by mouth at bedtime once daily

Also known as: sugar pill

Sugar pill

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead

Study Sites (1)

Penn State University hershey Medical center

Hershey, Pennsylvania, 17033, United States

Location

Related Publications (3)

• 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.

  PMID: 17222320 BACKGROUND

• 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.

  PMID: 21380937 BACKGROUND

• 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.

  PMID: 23188075 RESULT

Related Links

• Penn State College of Medicine- Clinical Trials Office Site

MeSH Terms

Conditions

Crohn Disease; Inflammatory Bowel Diseases

Interventions

Naltrexone; vivitrol; Sugars

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Carbohydrates

Limitations and Caveats

This was a pseudo-crossover trial where 6 subjects received placebo for 8 wks then were crossed over to active drug for 8 wks to increase the N treated with active drug. A smaller cohort of subjects on placebo were for safety \& toxicity comparison.

Results Point of Contact

• Title: Jill P Smith, MD Professor Emeritus of medicine
• Organization: Pennsylvania State University

jsmith2@psu.edu

717-531-3694

Study Officials

• Jill P Smith, MD

  Pennsylvania State University College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2008
• First Posted: July 15, 2008
• Study Start: July 1, 2008
• Primary Completion: May 1, 2010
• Study Completion: August 1, 2010
• Last Updated: September 6, 2018
• Results First Posted: May 30, 2013

Record last verified: 2013-05

Locations

US (1)