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The Effects of Naltrexone on Active Crohn's Disease (LDN)

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ClinicalTrials.gov Identifier: NCT00663117
Recruitment Status : Completed
First Posted : April 22, 2008
Results First Posted : May 17, 2013
Last Update Posted : October 2, 2018
Sponsor:
Collaborators:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
The Broad Foundation
Information provided by (Responsible Party):
Milton S. Hershey Medical Center

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Inflammation
Crohn's Disease
Interventions Drug: Naltrexone-HCl
Drug: Placebo
Enrollment 40
Recruitment Details This prospective, double blind, randomized placebo-controlled trial, undertaken between September 2006 and September 2009 at the Pennsylvania State University College of Medicine.
Pre-assignment Details  
Arm/Group Title Placebo Then Naltrexone 4.5 mg Daily Naltrexone Then Naltrexone 4.5 mg po Daily
Hide Arm/Group Description Subjects will receive placebo for 3 months then be crossed over to active drug for an additional 3 months Group 2 will receive naltrexone 4.5 mg by mouth once a day for 6 months
Period Title: Overall Study
Started 20 20
Completed 19 [1] 20
Not Completed 1 0
Reason Not Completed
Lack of Efficacy             1             0
[1]
One patient in placebo flared and was unblinded and crossed over to active drug
Arm/Group Title Placebo Daily Naltrexone 4.5 mg po Daily Total
Hide Arm/Group Description Subjects will receive placebo for 3 months then be crossed over to active drug for an additional 3 months Group 2 will receive naltrexone 4.5 mg by mouth once a day for 6 months Total of all reporting groups
Overall Number of Baseline Participants 20 20 40
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 20 participants 40 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
19
  95.0%
20
 100.0%
39
  97.5%
>=65 years
1
   5.0%
0
   0.0%
1
   2.5%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 20 participants 20 participants 40 participants
44.8  (2.8) 40.5  (2.4) 42.3  (2.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 20 participants 40 participants
Female
11
  55.0%
12
  60.0%
23
  57.5%
Male
9
  45.0%
8
  40.0%
17
  42.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 20 participants 20 participants 40 participants
20 20 40
Crohn's Disease Activity Index (CDAI) score   [1] 
Mean (Standard Deviation)
Unit of measure:  CDAI score
Number Analyzed 20 participants 20 participants 40 participants
327  (19) 365  (16) 346  (17.5)
[1]
Measure Description: 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.
1.Primary Outcome
Title Percentage of Subjects Achieving a 70-point Decline in CDAI Scores (Crohn's Disease Activity Index) Scores;
Hide Description 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.
Time Frame 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Naltrexone 4.5 mg po Daily
Hide Arm/Group Description:
Placebo 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
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
Overall Number of Participants Analyzed 20 20
Measure Type: Number
Unit of Measure: percentage of pts
40 88
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Naltrexone 4.5 mg po Daily
Comments The proportion of those achieving a response with a 70-point decline in CDAI score was compared between naltrexone and placebo treated subjects using the Fisher’s exact test. Analysis was performed with the intent-to-treat criteria. Clinical significance was accepted if the difference met 95% confidence (p<0.05).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.009
Comments The percentage of subjects achieving a 70-point drop in CDAI score in naltrexone treated subjects was the percentage acheiving the same drop in the placebo controls
Method Fisher Exact
Comments [Not Specified]
2.Secondary Outcome
Title Percentage Change From Baseline of Quality of Life IBDQ (Inflammatory Bowel Disease Quality of Life Survey)
Hide Description 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.
Time Frame Between baseline and 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
Same as sample size calculation
Arm/Group Title Placebo Naltrexone 4.5 mg po Daily
Hide Arm/Group Description:
Quality of life in subjects on placebo treatment for 12 weeks
Quality of life on naltrexone treatment 12 weeks
Overall Number of Participants Analyzed 20 20
Mean (Standard Error)
Unit of Measure: percentage of change
18  (4) 28  (5)
3.Secondary Outcome
Title Percentage of Patients With a 5 Point Drop in CDEIS Score by Endoscopy
Hide Description 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.
Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Naltrexone 4.5 mg
Hide Arm/Group Description:
Placebo for 12 weeks blinded followed by naltrexone 4.5mg open labeled
naltrexone 4.5 mg for 12 weeks blinded followed by naltrexone 4.5 mg open labeled
Overall Number of Participants Analyzed 20 20
Measure Type: Number
Unit of Measure: percentage of patients
28 78
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Naltrexone 4.5 mg
Comments Percentage of patients having a 5-point decline in the endoscopic inflammation score
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
4.Secondary Outcome
Title Histology Inflammatory Score by Colon Biopsies
Hide Description 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..
Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Tissue was removed by biopsy in those undergoing colonoscopy
Arm/Group Title Placebo Naltrexone 4.5 mg po Daily
Hide Arm/Group Description:
Subjects who received placebo for 3 months
Subjects who received naltrexone 4.5 mg by mouth once a day for 3 months
Overall Number of Participants Analyzed 20 20
Mean (Standard Error)
Unit of Measure: units on a scale
17.5  (4.5) 5.2  (2.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Naltrexone 4.5 mg po Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.048
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Naltrexone 4.5 mg
Hide Arm/Group Description Participants who received placebo for the first 12 weeks. All participants who received naltrexone either for 12 or 24 weeks.
All-Cause Mortality
Placebo Naltrexone 4.5 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Naltrexone 4.5 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/20 (0.00%)      0/40 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Naltrexone 4.5 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/20 (25.00%)      5/40 (12.50%)    
General disorders     
Fatigue  [1]  3/20 (15.00%)  3 0/40 (0.00%)  0
Nervous system disorders     
insomnia   5/20 (25.00%)  5 5/40 (12.50%)  5
Indicates events were collected by systematic assessment
[1]
Placebo-treated subjects had increased fatigue (p = 0.04).
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Jill P Smith, MD Professor of Medicine, Gastroenterology Division
Organization: Pennsylvania State University, College of Medicine Hershey, PA 17033
Phone: 717-531-3694
Responsible Party: Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier: NCT00663117     History of Changes
Other Study ID Numbers: DK073614 l
1R03DK073614 ( U.S. NIH Grant/Contract )
IBD-0180R ( Other Grant/Funding Number: Broad Medical Research Program )
First Submitted: April 18, 2008
First Posted: April 22, 2008
Results First Submitted: November 30, 2012
Results First Posted: May 17, 2013
Last Update Posted: October 2, 2018