Efficacy Study of Targeted, Local Delivery of Drugs to Treat Crohn's Disease - Full Text View

Sponsored by:	Teva R&D Initiative
Information provided by:	Teva R&D Initiative
ClinicalTrials.gov Identifier:	NCT00287170

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 I Phase II

Genetics Home Reference related topics: Crohn disease

MedlinePlus related topics: Crohn's Disease

Drug Information available for: 6-Mercaptopurine Calcitriol Mercaptopurine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
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

Further study details as provided by Teva R&D Initiative:

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

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

Locations

Israel
Hadassah Medical Center
Jerusalem, Israel, 91120

Sponsors and Collaborators

Teva R&D Initiative

Investigators

Principal Investigator:

Yaron Ilan, MD

Hadassah Medical Center

More Information

No publications provided

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

Keywords provided by Teva R&D Initiative:

Crohn's Disease
Local Ileal Delivery
Delayed-Release Formulations
6-Mercaptopurine
Calcitriol

Study placed in the following topic categories:

Antimetabolites
Crohn's Disease
Immunologic Factors
Ileitis
Gastrointestinal Diseases
Enteritis
Inflammatory Bowel Diseases
Bone Density Conservation Agents
Trace Elements
Cardiovascular Agents
6-Mercaptopurine

Intestinal Diseases
Immunosuppressive Agents
Ileal Diseases
Calcitriol
Calcium, Dietary
Digestive System Diseases
Vitamins
Crohn Disease
Vasoconstrictor Agents
Micronutrients
Gastroenteritis

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Gastrointestinal Diseases
Antineoplastic Agents
Calcium Channel Agonists
Physiological Effects of Drugs
Inflammatory Bowel Diseases
Bone Density Conservation Agents
6-Mercaptopurine
Ileal Diseases
Calcitriol
Membrane Transport Modulators
Therapeutic Uses

Vitamins
Vasoconstrictor Agents
Micronutrients
Nucleic Acid Synthesis Inhibitors
Ileitis
Enteritis
Growth Substances
Enzyme Inhibitors
Cardiovascular Agents
Intestinal Diseases
Immunosuppressive Agents
Pharmacologic Actions
Digestive System Diseases
Crohn Disease
Gastroenteritis

ClinicalTrials.gov processed this record on May 07, 2009