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

Primary Purpose

Inflammation, Crohn's Disease

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Naltrexone-HCl
Placebo
Sponsored by
Milton S. Hershey Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Inflammation focused on measuring naltrexone, LDN, IBD, Inflammatory bowel disease

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Penn State Hershey Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo, Sugar pill

Naltrexone-HCl

Arm Description

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

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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..

Full Information

First Posted
April 18, 2008
Last Updated
September 4, 2018
Sponsor
Milton S. Hershey Medical Center
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), The Broad Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT00663117
Brief Title
The Effects of Naltrexone on Active Crohn's Disease
Acronym
LDN
Official Title
The Effects of Naltrexone in Active Crohn's Disease
Study Type
Interventional

2. Study Status

Record Verification Date
May 2013
Overall Recruitment Status
Completed
Study Start Date
September 2006 (undefined)
Primary Completion Date
October 2009 (Actual)
Study Completion Date
October 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Milton S. Hershey Medical Center
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), The Broad Foundation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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: 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Inflammation, Crohn's Disease
Keywords
naltrexone, LDN, IBD, Inflammatory bowel disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo, Sugar pill
Arm Type
Placebo Comparator
Arm Description
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
Arm Title
Naltrexone-HCl
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Naltrexone-HCl
Other Intervention Name(s)
LDN, Revia
Intervention Description
naltrexone 4.5 mg
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
sugar pill
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Percentage of Subjects Achieving a 70-point Decline in CDAI Scores (Crohn's Disease Activity Index) Scores;
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
Secondary Outcome Measure Information:
Title
Percentage Change From Baseline of Quality of Life IBDQ (Inflammatory Bowel Disease Quality of Life Survey)
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
Title
Percentage of Patients With a 5 Point Drop in CDEIS Score by Endoscopy
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
Title
Histology Inflammatory Score by Colon Biopsies
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jill P. Smith, M.D.
Organizational Affiliation
Pennsylvania State University College of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Penn State Hershey Medical Center
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
17222320
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. doi: 10.1111/j.1572-0241.2007.01045.x. Epub 2007 Jan 11.
Results Reference
background
PubMed Identifier
21380937
Citation
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.
Results Reference
result
Links:
URL
http://www.hmc.psu.edu/clinicaltrials/studies/gi/index.htm
Description
Penn State Hershey Clinical Trials Website

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The Effects of Naltrexone on Active Crohn's Disease

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