The Effects of Naltrexone on Active Crohn's Disease

Inflammation Clinical Trial

— LDN  

Official title:

The Effects of Naltrexone in Active Crohn's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00663117
• Other study ID #: DK073614 l
• Secondary ID: 1R03DK073614IBD-
• Status: Completed
• Phase: Phase 2
• Start date: September 2006
• Est. completion date: October 2009

Study information

• Verified date: May 2013
• Source: Milton S. Hershey Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: October 2009
• Est. primary completion date: October 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease
• Inflammation

Intervention

Drug:
• Naltrexone-HCl
naltrexone 4.5 mg
• Placebo
Placebo

Locations

Country	Name	City	State
United States	Penn State Hershey Medical Center	Hershey	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Milton S. Hershey Medical Center	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), The Broad Foundation

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View 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. Epub 2007 Jan 11. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Subjects Achieving a 70-point Decline in CDAI Scores (Crohn's Disease Activity Index) Scores;	The CDAI score is a number which consists of information collected from a 7-day diary from the patient regarding symptoms. It also includes objective information from the physical exam, weight and hemotocrit. Remission is considered a score of 150 or less. Active disease is considered 220 or greater. A response to therapy is considered a decline in the CDAI score of 70-points from baseline.	3 months
Secondary	Percentage Change From Baseline of Quality of Life IBDQ (Inflammatory Bowel Disease Quality of Life Survey)	IBDQ (Inflammatory bowel Disease questionnaire) contains questions about health ranging from a score of poor (i.e., 32) to excellent (i.e., 224) an increase from baseline indicates improvement in quality of life.	Between baseline and 3 months
Secondary	Percentage of Patients With a 5 Point Drop in CDEIS Score by Endoscopy	A secondary outcome was the appearance of the colonic mucosa on endoscopy using the Crohn's Disease Endoscopic Index of Severity (CDEIS) score described by Mary et al. Gut 1989;30:983-989.This score ranges from 0-44 based upon the extent and severity of inflammation and ulcers seen during endoscopy of the colon. A response is a drop of > 5 points from baseline. Endoscopic remission is a score of < 6 and Complete endoscopic remission is a score of > 3.	12 weeks
Secondary	Histology Inflammatory Score by Colon Biopsies	Histology scores to assess microscopic inflammation and structural architecture were determined at baseline and after 12 weeks of either naltrexone therapy or placebo by mucosal biopsy samples obtained during colonoscopies.The pathology specimens were reviewed and scored by a Pathologist blinded to the treatment. The mean scores at baseline were the same between both groups.Differences between naltrexone and placebo treated subjects was assessed.The range in scores could be 0-25, with 0 representing no inflammation and 25 being maximum or severe inflammation..	12 weeks

External Links

•   Penn State Hershey Clinical Trials Website