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

This study has been completed.
Sponsor:
Information provided by:
Teva GTC
ClinicalTrials.gov Identifier:
NCT00287170
First received: February 2, 2006
Last updated: July 3, 2008
Last verified: July 2008
  Purpose

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.


Condition Intervention Phase
Crohn's Disease
Drug: Delayed Release 6MP or Calcitriol vs. Purinethol
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Teva GTC:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • Improvement in ESR (Erythrocyte Sedimentation Rate), CRP (C-Reactive Protein) levels, and IBDQ (Inflammatory Bowel Disease Questionnaire) >=180 indicative of remission

Enrollment: 15
Study Start Date: July 2006
Study Completion Date: December 2007
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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00287170

Locations
Israel
Hadassah Medical Center
Jerusalem, Israel, 91120
Sponsors and Collaborators
Teva GTC
Investigators
Principal Investigator: Yaron Ilan, MD Hadassah Medical Center
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00287170     History of Changes
Other Study ID Numbers: C2/13/6MP:CAL-01
Study First Received: February 2, 2006
Last Updated: July 3, 2008
Health Authority: Israel: Ministry of Health

Keywords provided by Teva GTC:
Crohn's Disease
Local Ileal Delivery
Delayed-Release Formulations
6-Mercaptopurine
Calcitriol

Additional relevant MeSH terms:
Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
6-Mercaptopurine
Calcitriol
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Vitamins
Micronutrients
Growth Substances
Bone Density Conservation Agents
Calcium Channel Agonists
Membrane Transport Modulators
Vasoconstrictor Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on July 28, 2014