The Effects of Naltrexone on Active Crohn's Disease

NCT ID: NCT00663117

Last Updated: 2018-10-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-09-30
• Study Completion Date: 2009-10-31

Brief Summary

It is hypothesized that the opioid antagonist naltrexone will improve inflammation of the bowel and quality of life in subjects with active Crohn's disease compared to placebo. In order to test this hypothesis the following specific aims are proposed:

1. Evaluate the effects of low dose naltrexone compared to placebo on the activity of Crohn's disease by the following end points: Crohn's Disease Activity Index (CDAI), pain assessment, laboratory values (CRP and ESR), endoscopic appearance, histology, and quality of life surveys;

2. Examine the effects of naltrexone given over 3 months compared to 6 months for durability of response;

3. Determine the safety and toxicity of low dose naltrexone in subjects with active Crohn's disease, and

4. Study the mechanism by which naltrexone exerts its effect by measuring plasma enkephalin levels of subjects on therapy.

Purpose statement: The purpose of this study is to evaluate the effects of low dose naltrexone in a blinded placebo controlled study to determine the safety and efficacy of this compound in those with active Crohn's disease.

Detailed Description

Study design : The study is designed as a double-blind placebo controlled study for 3 months followed by a pseudo cross-over such that all subjects receiving placebo the first 3 months will receive active drug the second 3 months and all receiving naltrexone the first 3 months remain on the drug the last 3 months of this 6 month study.

Conditions

Inflammation; Crohn's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo, Sugar pill

placebo for 3 months blinded then followed by an open-labelled study and all are treated with naltrexone 4.5 mg for 3 additional months

Group Type: PLACEBO_COMPARATOR

Naltrexone-HCl

Intervention Type: DRUG

naltrexone 4.5 mg

Placebo

Intervention Type: DRUG

Placebo

Naltrexone-HCl

Subjects are treated in a blinded fashion for 3 months with naltrexone 4.5 mg po for active Crohn's disease followed an open-labelled study where naltrexone is given an additional 3 months at 4.5 mg po; hence the total treatment interval in this arm is 6 months. The response to the intervention administered is measured in the activity index and mucosal healing by colonoscopy.

Group Type: ACTIVE_COMPARATOR

Naltrexone-HCl

Intervention Type: DRUG

naltrexone 4.5 mg

Interventions

Naltrexone-HCl

naltrexone 4.5 mg

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Other Intervention Names

LDN; Revia; sugar pill

Eligibility Criteria

Inclusion Criteria

• All subjects must give written informed consent
• Male or female subjects, > 18 years
• Patients must have endoscopic, histologic, or radiographic confirmed Crohn's Disease.
• Patients must have a Crohn's Disease Activity Index (CDAI) of at least 220 at Baseline
• Stable doses of medications for Crohn's disease over proceeding 4 weeks (for aminosalicylates and steroids: prednisone of 10mg or less daily and Entocort 3 mg/ day are allowed), and 12 weeks for azathioprine or 6-mercaptopurine.)

Exclusion Criteria

• Subjects with ostomies or ileorectal anastomosis from prior surgical colectomy.
• Subjects who received infliximab (Remicade) within 8 weeks of study screening or humira for 4 weeks.
• Subjects requiring steroids either intravenously or prednisone >10mg /day or Entocort > 3 mg daily.
• Subjects with short-bowel syndrome.
• Abnormal liver enzymes at screening visit or known hepatitis or cirrhosis
• Hemoglobin less than 10.
• Subjects with cancer (other than skin cancer) in past 5 years.
• Women of childbearing potential 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.
• Women who are pregnant or breastfeeding

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

The Broad Foundation

OTHER

Sponsor Role: collaborator

Milton S. Hershey Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jill P. Smith, M.D.

Role: PRINCIPAL_INVESTIGATOR

Pennsylvania State University College of Medicine

Locations

Penn State Hershey Medical Center

Hershey, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 17222320 (View on PubMed)

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.

Reference Type: RESULT

PMID: 21380937 (View on PubMed)

Related Links

http://www.hmc.psu.edu/clinicaltrials/studies/gi/index.htm

Penn State Hershey Clinical Trials Website

Other Identifiers

1R03DK073614

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IBD-0180R

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

DK073614 l

Identifier Type: -

Identifier Source: org_study_id