Trial Outcomes & Findings for The Effects of Naltrexone on Active Crohn's Disease (NCT NCT00663117)

NCT ID: NCT00663117

Last Updated: 2018-10-02

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

40 participants

Primary outcome timeframe

3 months

Results posted on

2018-10-02

Participant Flow

This prospective, double blind, randomized placebo-controlled trial, undertaken between September 2006 and September 2009 at the Pennsylvania State University College of Medicine.

Participant milestones

Participant milestones
Measure
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
Naltrexone Then Naltrexone 4.5 mg po Daily
Group 2 will receive naltrexone 4.5 mg by mouth once a day for 6 months
Overall Study
STARTED
20
20
Overall Study
COMPLETED
19
20
Overall Study
NOT COMPLETED
1
0

Reasons for withdrawal

Reasons for withdrawal
Measure
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
Naltrexone Then Naltrexone 4.5 mg po Daily
Group 2 will receive naltrexone 4.5 mg by mouth once a day for 6 months
Overall Study
Lack of Efficacy
1
0

Baseline Characteristics

The Effects of Naltrexone on Active Crohn's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Placebo Daily
n=20 Participants
Subjects will receive placebo for 3 months then be crossed over to active drug for an additional 3 months
Naltrexone 4.5 mg po Daily
n=20 Participants
Group 2 will receive naltrexone 4.5 mg by mouth once a day for 6 months
Total
n=40 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
19 Participants
n=5 Participants
20 Participants
n=7 Participants
39 Participants
n=5 Participants
Age, Categorical
>=65 years
1 Participants
n=5 Participants
0 Participants
n=7 Participants
1 Participants
n=5 Participants
Age, Continuous
44.8 years
STANDARD_DEVIATION 2.8 • n=5 Participants
40.5 years
STANDARD_DEVIATION 2.4 • n=7 Participants
42.3 years
STANDARD_DEVIATION 2.5 • n=5 Participants
Sex: Female, Male
Female
11 Participants
n=5 Participants
12 Participants
n=7 Participants
23 Participants
n=5 Participants
Sex: Female, Male
Male
9 Participants
n=5 Participants
8 Participants
n=7 Participants
17 Participants
n=5 Participants
Region of Enrollment
United States
20 participants
n=5 Participants
20 participants
n=7 Participants
40 participants
n=5 Participants
Crohn's Disease Activity Index (CDAI) score
327 CDAI score
STANDARD_DEVIATION 19 • n=5 Participants
365 CDAI score
STANDARD_DEVIATION 16 • n=7 Participants
346 CDAI score
STANDARD_DEVIATION 17.5 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Placebo
n=20 Participants
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 4.5 mg po Daily
n=20 Participants
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
Percentage of Subjects Achieving a 70-point Decline in CDAI Scores (Crohn's Disease Activity Index) Scores;
40 percentage of pts
88 percentage of pts

SECONDARY outcome

Timeframe: Between baseline and 3 months

Population: Same as sample size calculation

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.

Outcome measures

Outcome measures
Measure
Placebo
n=20 Participants
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 4.5 mg po Daily
n=20 Participants
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
Percentage Change From Baseline of Quality of Life IBDQ (Inflammatory Bowel Disease Quality of Life Survey)
18 percentage of change
Standard Error 4
28 percentage of change
Standard Error 5

SECONDARY outcome

Timeframe: 12 weeks

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Placebo
n=20 Participants
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 4.5 mg po Daily
n=20 Participants
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
Percentage of Patients With a 5 Point Drop in CDEIS Score by Endoscopy
28 percentage of patients
Interval 0.0 to 100.0
78 percentage of patients
.05 • Interval 0.0 to 100.0

SECONDARY outcome

Timeframe: 12 weeks

Population: Tissue was removed by biopsy in those undergoing colonoscopy

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..

Outcome measures

Outcome measures
Measure
Placebo
n=20 Participants
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 4.5 mg po Daily
n=20 Participants
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
Histology Inflammatory Score by Colon Biopsies
17.5 units on a scale
Standard Error 4.5
5.2 units on a scale
Standard Error 2.3

Adverse Events

Placebo

Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths

Naltrexone 4.5 mg

Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Placebo
n=20 participants at risk
Participants who received placebo for the first 12 weeks.
Naltrexone 4.5 mg
n=40 participants at risk
All participants who received naltrexone either for 12 or 24 weeks.
Nervous system disorders
insomnia
25.0%
5/20 • Number of events 5
12.5%
5/40 • Number of events 5
General disorders
Fatigue
15.0%
3/20 • Number of events 3
0.00%
0/40

Additional Information

Jill P Smith, MD Professor of Medicine, Gastroenterology Division

Pennsylvania State University, College of Medicine Hershey, PA 17033

Phone: 717-531-3694

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place