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| ID | Type | Description | Link |
|---|---|---|---|
| 1R03DK073614 | U.S. NIH Grant/Contract | View source | |
| IBD-0180R | Other Grant/Funding Number | Broad Medical Research Program |
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| Name | Class |
|---|---|
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
| The Broad Foundation | OTHER |
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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:
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 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo, Sugar pill | Placebo Comparator | 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 |
|
| Naltrexone-HCl | Active Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Naltrexone-HCl | Drug | naltrexone 4.5 mg |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jill P. Smith, M.D. | Pennsylvania State University College of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Penn State Hershey Medical Center | Hershey | Pennsylvania | 17033 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17222320 | Background | 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. | |
| 21380937 | Result | 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. |
| Label | URL |
|---|---|
| Penn State Hershey Clinical Trials Website | View source |
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This prospective, double blind, randomized placebo-controlled trial, undertaken between September 2006 and September 2009 at the Pennsylvania State University College of Medicine.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo Then Naltrexone 4.5 mg Daily | Subjects will receive placebo for 3 months then be crossed over to active drug for an additional 3 months |
| FG001 | Naltrexone Then Naltrexone 4.5 mg po Daily | Group 2 will receive naltrexone 4.5 mg by mouth once a day for 6 months |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo Daily | Subjects will receive placebo for 3 months then be crossed over to active drug for an additional 3 months |
| BG001 | Naltrexone 4.5 mg po Daily | Group 2 will receive naltrexone 4.5 mg by mouth once a day for 6 months |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Number | percentage of pts | 3 months |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Participants who received placebo for the first 12 weeks. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| insomnia | Nervous system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jill P Smith, MD Professor of Medicine, Gastroenterology Division | Pennsylvania State University, College of Medicine Hershey, PA 17033 | 717-531-3694 | jsmith2@psu.edu |
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| ID | Term |
|---|---|
| D007249 | Inflammation |
| D003424 | Crohn Disease |
| D015212 | Inflammatory Bowel Diseases |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
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| ID | Term |
|---|---|
| D009271 | Naltrexone |
| D000073893 | Sugars |
| ID | Term |
|---|---|
| D009270 | Naloxone |
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
| D006571 |
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| Placebo | Drug | Placebo |
|
|
| 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 |
| 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 |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
|
| Crohn's Disease Activity Index (CDAI) score | The CDAI score is a number unit calculated from symptoms recorded by the subject over a 7-day period before each visit, weight, hemoglobin, and physical exam findings. The score ranges from 0 to 450. A score of 220 is considered 'active' disease. A score of 150 is considered "remission." A drop of 70-points in the score is considered a "response" to therapy. | Mean | Standard Deviation | CDAI score |
|
Naltrexone treated subjects for 12 weeks were analyzed for the percentage that achieved the primary outcome of a 70-point decline in the CDAI score from Baseline values |
|
|
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| 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. | Same as sample size calculation | Posted | Mean | Standard Error | percentage of change | 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. | Sample size was calculated under the assumption that at least 60% of the naltrexone-treated patients, and no more than 10% of the placebo-treated patients, would respond with at least a 70-point decline in CDAI scores. With a 10% withdrawal rate, 40 subjects yields an 86% power using a two-sided, 0.05-significance level Fisher's exact test. | Posted | Number | percentage of patients | 12 weeks |
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| 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.. | Tissue was removed by biopsy in those undergoing colonoscopy | Posted | Mean | Standard Error | units on a scale | 12 weeks |
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|
| 0 |
| 20 |
| 5 |
| 20 |
| EG001 | Naltrexone 4.5 mg | All participants who received naltrexone either for 12 or 24 weeks. | 0 | 40 | 5 | 40 |
| Fatigue | General disorders | Systematic Assessment | Placebo-treated subjects had increased fatigue (p = 0.04). |
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| D004066 | Digestive System Diseases |
| D007410 | Intestinal Diseases |
| Heterocyclic Compounds |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D002241 | Carbohydrates |