The Effects of Naltrexone on Active Crohn's Disease

NCT00663117 | Completed Phase 2 Results DMC

• 3 other identifiers: DK073614 l1R03DK073614IBD-0180R
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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:

1. 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. 2.Examine the effects of naltrexone given over 3 months compared to 6 months for durability of response;
3. 3.Determine the safety and toxicity of low dose naltrexone in subjects with active Crohn's disease, and
4. 4.Study the mechanism by which naltrexone exerts its effect by measuring plasma enkephalin levels of subjects on therapy.

Conditions

Inflammation; Crohn's Disease

Keywords

naltrexone; LDN; IBD; Inflammatory bowel disease

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (3)

• Percentage Change From Baseline of Quality of Life IBDQ (Inflammatory Bowel Disease Quality of Life Survey)

  Between baseline and 3 months

• Percentage of Patients With a 5 Point Drop in CDEIS Score by Endoscopy

  12 weeks

• Histology Inflammatory Score by Colon Biopsies

  12 weeks

Study Arms (2)

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

Drug: Naltrexone-HCl; Drug: Placebo

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.

Drug: Naltrexone-HCl

Interventions

Naltrexone-HCl DRUG

naltrexone 4.5 mg

Also known as: LDN, Revia

Naltrexone-HCl; Placebo, Sugar pill

Placebo DRUG

Placebo

Also known as: sugar pill

Placebo, Sugar pill

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.)

You may not qualify if:

• 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

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• The Broad Foundation: collaborator

Study Sites (1)

Penn State Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Related Publications (2)

• 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.

  PMID: 17222320 BACKGROUND

• 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.

  PMID: 21380937 RESULT

Related Links

• Penn State Hershey Clinical Trials Website

MeSH Terms

Conditions

Inflammation; Crohn Disease; Inflammatory Bowel Diseases

Interventions

Naltrexone; Sugars

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Carbohydrates

Results Point of Contact

• Title: Jill P Smith, MD Professor of Medicine, Gastroenterology Division
• Organization: Pennsylvania State University, College of Medicine Hershey, PA 17033

jsmith2@psu.edu

717-531-3694

Study Officials

• Jill P. Smith, M.D.

  Pennsylvania State University College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2008
• First Posted: April 22, 2008
• Study Start: September 1, 2006
• Primary Completion: October 1, 2009
• Study Completion: October 1, 2009
• Last Updated: October 2, 2018
• Results First Posted: May 17, 2013

Record last verified: 2013-05

Locations

US (1)