Efficacy Study of Targeted, Local Delivery of Drugs to Treat Crohn's Disease
Information source: Teva GTC
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Crohn's Disease
Intervention: Delayed Release 6MP or Calcitriol vs. Purinethol (Drug)
Phase: Phase 1/Phase 2
Status: Completed
Sponsored by: Teva GTC Official(s) and/or principal investigator(s): Yaron Ilan, MD, Principal Investigator, Affiliation: Hadassah Medical Center
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.
Clinical Details
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
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Remission-defined as a CDAI (Crohn's Disease Activity Index) of <150Response- defined as a fall in the CDAI by 100 points or more from baseline
Secondary outcome: Improvement in ESR (Erythrocyte Sedimentation Rate), CRP (C-Reactive Protein) levels, and IBDQ (Inflammatory Bowel Disease Questionnaire) >=180 indicative of remission
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
Minimum age: 18 Years.
Maximum age: 75 Years.
Gender(s): Both.
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
Locations and Contacts
Hadassah Medical Center, Jerusalem 91120, Israel
Additional Information
Starting date: July 2006
Last updated: July 3, 2008
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