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Efficacy Study of Targeted, Local Delivery of Drugs to Treat Crohn's Disease

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ClinicalTrials.gov Identifier: NCT00287170
Recruitment Status : Completed
First Posted : February 6, 2006
Last Update Posted : July 8, 2008
Sponsor:
Information provided by:
Teva GTC

Tracking Information
First Submitted Date  ICMJE February 2, 2006
First Posted Date  ICMJE February 6, 2006
Last Update Posted Date July 8, 2008
Study Start Date  ICMJE July 2006
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE
 (submitted: September 10, 2007)
  • Remission-defined as a CDAI (Crohn's Disease Activity Index) of <150 [ Time Frame: 12 weeks ]
  • Response- defined as a fall in the CDAI by 100 points or more from baseline [ Time Frame: 12 weeks ]
Original Primary Outcome Measures  ICMJE
 (submitted: February 2, 2006)
  • Remission-defined as a CDAI (Crohn's Disease Activity Index) of <150
  • Response- defined as a fall in the CDAI by 100 points or more from baseline
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 2, 2006)
Improvement in ESR (Erythrocyte Sedimentation Rate), CRP (C-Reactive Protein) levels, and IBDQ (Inflammatory Bowel Disease Questionnaire) >=180 indicative of remission
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy Study of Targeted, Local Delivery of Drugs to Treat Crohn's Disease
Official Title  ICMJE Pilot, Open-Label, Randomized, Parallel Group Study to Evaluate Clinical/ and Immunological Efficacy/Safety of Locally Delivered 6-MP or Calcitriol vs Purinethol in Non-Steroid Dependent Patients With Active CD
Brief Summary

The study is being undertaken to evaluate whether delayed-release medications, designed to begin to open in the lower intestinal tract, the main site of Crohn's Disease, are more effective than standard systemically delivered drugs to promote remission or response in CD patients. It is hypothesized that the delayed-release medications will go right to the injured tissue and heal the disease more quickly.

The delayed-release test drugs are 6-mercaptopurine (at a dose of 40 mg daily) or calcitriol (at a dose of 5 mcg three times a week) versus Purinethol (6-MP at a dose of 1-2 mg/kg body weight daily). Calcitriol is a synthetically manufactured replica of a natural substance in the body that is derived from Vitamin D. There is much medical evidence that shows that lack of Vitamin D can be a possible risk factor in developing autoimmune disorders, including Crohn's Disease. Moreover, calcitriol has been shown in animal models to improve the symptoms of Crohn's Disease.

Detailed Description

This pilot clinical study is designed to evaluate the efficacy and safety of oral administration of novel, delayed-release test formulations, for targeted delivery to the ileum in Crohn's Disease patients. The local delivery drugs (delayed-release formulations of 6-mercaptopurine or calcitriol) will be compared to standard Purinethol treatment after 12 weeks of treatment to evaluate:

  • (1) local intestinal mucosal inflammation and damage as shown by markers of biopsy tissue (CDEIS and pathologist review of biopsies);
  • (2) Clinical symptoms of active Crohn's Disease [CDAI scores- remission <150; response- a drop of 100 points from baseline; IBDQ scores- >= 180 indicative of remission]; and
  • (3)Systemic improvement as shown by blood immunological and inflammatory markers (CRP and ESR).

It is hypothesized that since CD is a localized autoimmune inflammation of the intestinal mucosa, a far more effective, and potentially safer treatment would be targeted, local delivery of effective drugs directly to the disease site. The drug would be concentrated in the specific area of disease, while unwanted systemic side effects would be minimized. The drugs selected for evaluation are 6-MP (a mainstay of CD treatment for over 30 years) and calcitriol, a synthetically manufactured Vitamin D derivative, which is being evaluated in many studies for its impressive immunomodulatory effects in cancer, MS and other autoimmune disorders.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Crohn's Disease
Intervention  ICMJE Drug: Delayed Release 6MP or Calcitriol vs. Purinethol
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 2, 2006)
15
Original Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 2007
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male or Female patients, aged 18-75 years with moderate Crohn's Disease (CDAI score >=220 and <=400 at screening), with or without adjunctive mesalamine treatment, 12 with involvement of the ileum and three without ileal involvement
  • Definitive diagnosis of active inflammatory CD with fibrostenosing and/or fistulizing/perforating CD types ruled out based on clinical and radiological or endoscopic or pathological findings, within the previous 6 months

Exclusion Criteria:

  • Body weight below 42.5 kg
  • Subjects who have received either methotrexate, cyclosporine or anti-TNFalpha (infliximab, Remicade), anti-integrin (namixilab) in the past 3 months
  • Subjects who are taking allopurinol, sulfasalazine, valerian, warfarin and corticosteroids,including budesonide and prednisone within 28 days prior to and throughout the study
  • Previous bowel resection, including prior colostomy, ileostomy or colectomy with ileorectal anastomosis
  • Symptomatic stenosis or ileal strictures; x-ray evidence of fibrosed bowel
  • Subjects with ulcerative colitis or short bowel syndrome
  • Subjects who present with, or with a history of persistent intestinal obstruction, bowel perforation, uncontrolled GI bleed or abdominal abscess or infection, toxic megacolon
  • Subjects with fistulizing CD or isolated small bowel CD
  • Subjects with evidence of other serious infectious, autoimmune, hepatic,nephritic or systemic disease or compromised organ function
  • Subjects with a history of GI tract malignancy or IBD-associated malignant changes in the intestines
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Israel
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00287170
Other Study ID Numbers  ICMJE C2/13/6MP:CAL-01
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE Teva GTC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Yaron Ilan, MD Hadassah Medical Center
PRS Account Teva GTC
Verification Date July 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP