Efficacy Study of Targeted, Local Delivery of Drugs to Treat Crohn's Disease
Condition: Crohn's Disease
MeSH terms: Crohn Disease
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

Intervention name(s): Delayed Release 6MP or Calcitriol vs. Purinethol
Intervention type(s): Drug
Intervention MeSH terms: Calcitriol; Mercaptopurine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Crohn's Disease; Local Ileal Delivery; Delayed-Release Formulations; 6-Mercaptopurine; Calcitriol