Clinical trial NCT00663117: The Effects of Naltrexone on Active Crohn's Disease
Official title: The Effects of Naltrexone in Active Crohn's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Inflammation
Crohn's Disease
Keywords: naltrexone
LDN
IBD
Inflammatory bowel disease
Lead sponsor: Milton S. Hershey Medical Center
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: The Broad Foundation
First posted: 2008-04-22
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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. 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.

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 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

Primary outcomes:
measure: Percentage of Subjects Achieving a 70-point Decline in CDAI Scores (Crohn's Disease Activity Index) Scores;
timeFrame: 3 months
Secondary outcomes:
measure: Percentage Change From Baseline of Quality of Life IBDQ (Inflammatory Bowel Disease Quality of Life Survey)
timeFrame: Between baseline and 3 months
measure: Percentage of Patients With a 5 Point Drop in CDEIS Score by Endoscopy
timeFrame: 12 weeks
measure: Histology Inflammatory Score by Colon Biopsies
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
Study officials:
affiliation: Pennsylvania State University College of Medicine
name: Jill P. Smith, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.