The Effects of Naltrexone on Active Crohn's Disease

The Effects of Naltrexone in Active Crohn's Disease

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.

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.

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