- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00663117
The Effects of Naltrexone on Active Crohn's Disease (LDN)
The Effects of Naltrexone in Active Crohn's Disease
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:
- 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;
- Examine the effects of naltrexone given over 3 months compared to 6 months for durability of response;
- Determine the safety and toxicity of low dose naltrexone in subjects with active Crohn's disease, and
- 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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Pennsylvania
-
Hershey, Pennsylvania, United States, 17033
- Penn State Hershey Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: 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
|
Placebo
Other Names:
naltrexone 4.5 mg
Other Names:
|
Active Comparator: 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.
|
naltrexone 4.5 mg
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Subjects Achieving a 70-point Decline in CDAI Scores (Crohn's Disease Activity Index) Scores;
Time Frame: 3 months
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage Change From Baseline of Quality of Life IBDQ (Inflammatory Bowel Disease Quality of Life Survey)
Time Frame: Between baseline and 3 months
|
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.
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Between baseline and 3 months
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Percentage of Patients With a 5 Point Drop in CDEIS Score by Endoscopy
Time Frame: 12 weeks
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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
|
Histology Inflammatory Score by Colon Biopsies
Time Frame: 12 weeks
|
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
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Jill P. Smith, M.D., Pennsylvania State University College of Medicine
Publications and helpful links
General 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.
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Gastrointestinal Diseases
- Gastroenteritis
- Intestinal Diseases
- Inflammatory Bowel Diseases
- Inflammation
- Crohn Disease
- Physiological Effects of Drugs
- Peripheral Nervous System Agents
- Sensory System Agents
- Narcotic Antagonists
- Alcohol Deterrents
- Naltrexone
Other Study ID Numbers
- DK073614 l
- 1R03DK073614 (U.S. NIH Grant/Contract)
- IBD-0180R (Other Grant/Funding Number: Broad Medical Research Program)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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