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

This study has been completed.
Sponsor:
Collaborators:
The Broad Foundation
Information provided by (Responsible Party):
Jill P. Smith, Penn State University
ClinicalTrials.gov Identifier:
NCT00663117
First received: April 18, 2008
Last updated: May 16, 2013
Last verified: May 2013
  Purpose

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:

  1. 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;
  2. Examine the effects of naltrexone given over 3 months compared to 6 months for durability of response;
  3. Determine the safety and toxicity of low dose naltrexone in subjects with active Crohn's disease, and
  4. 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.


Condition Intervention Phase
Inflammation
Crohn's Disease
Drug: Naltrexone-HCl
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effects of Naltrexone in Active Crohn's Disease

Resource links provided by NLM:


Further study details as provided by Penn State University:

Primary Outcome Measures:
  • Percentage of Subjects Achieving a 70-point Decline in CDAI Scores (Crohn's Disease Activity Index) Scores; [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    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) [ Time Frame: Between baseline and 3 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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..


Enrollment: 40
Study Start Date: September 2006
Study Completion Date: October 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: Naltrexone-HCl
naltrexone 4.5 mg
Other Names:
  • LDN
  • Revia
Drug: Placebo
Placebo
Other Name: sugar pill
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.
Drug: Naltrexone-HCl
naltrexone 4.5 mg
Other Names:
  • LDN
  • Revia

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00663117

Locations
United States, Pennsylvania
Penn State Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Sponsors and Collaborators
Penn State University
The Broad Foundation
Investigators
Principal Investigator: Jill P. Smith, M.D. Pennsylvania State University College of Medicine
  More Information

Additional Information:
Publications:
Responsible Party: Jill P. Smith, Professor Emeritus of Medicine, Penn State University
ClinicalTrials.gov Identifier: NCT00663117     History of Changes
Other Study ID Numbers: DK073614 l, 1R03DK073614, IBD-0180R
Study First Received: April 18, 2008
Results First Received: November 30, 2012
Last Updated: May 16, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Penn State University:
naltrexone
LDN
IBD
Inflammatory bowel disease

Additional relevant MeSH terms:
Crohn Disease
Inflammation
Digestive System Diseases
Gastroenteritis
Gastrointestinal Diseases
Inflammatory Bowel Diseases
Intestinal Diseases
Pathologic Processes
Naltrexone
Central Nervous System Agents
Narcotic Antagonists
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014