Therapeutic Study of ONO-4819CD for Ulcerative Colitis - Full Text View

Sponsor:	Kyoto University, Graduate School of Medicine
Collaborator:	National Institute of Biomedical Innovation
Information provided by:	Kyoto University, Graduate School of Medicine
ClinicalTrials.gov Identifier:	NCT00296556

Purpose

The purpose of this study is to investigate whether ONO-4819CD is safe and effective in the treatment of mild to moderate ulcerative colitis.

Condition	Intervention	Phase
Ulcerative Colitis	Drug: Rivenprost (drug)	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Randomized, Placebo-Controlled Trial of ONO-4819CD for Treatment of Mild to Moderate Ulcerative Colitis.

Resource links provided by NLM:

Genetics Home Reference related topics: Crohn disease

MedlinePlus related topics: Ulcerative Colitis

Drug Information available for: Rivenprost

U.S. FDA Resources

Further study details as provided by Kyoto University, Graduate School of Medicine:

Primary Outcome Measures:

Remission evaluated by DAI scores at 14 and 28 days

Secondary Outcome Measures:

Improvement by DAI scores; Change in DAI scores; CAI scores at 3, 7, 14 and 28 days; Colonoscopic and histopathological scores at 14 and 28 days; Clinical severity and symptom scores at 7, 14 and 28 days; Cytokines at 7, 14 and 28 days; Adverse effects.

Enrollment:	7
Study Start Date:	February 2006
Study Completion Date:	March 2008
Estimated Primary Completion Date:	December 2007 (Final data collection date for primary outcome measure)

Detailed Description:

Ulcerative colitis is a relapsing disease of unknown cause characterized by bloody diarrhea. Therapy usually involves 5-aminosalicylates, corticosteroids and immunosuppressants. However, steroid resistance and dependency can become problematic. Immunosuppressive drugs, such as azathioprine, are beneficial but may have serious side effects. Therefore, new therapeutic approach is needed.

Prostaglandin E2 is one of the prostanoids, which is involved with innate immunity. PGE2 induces oral tolerance to specific antigen in the small intestine and downregulates the production and release of proinflammatory cytokines by macrophages and neutrophils. Accordingly, PGE2 is considered to be the mediator of mucosal protection.

Recently, it was elucidated that disruption of EP4 gene, which is one of PGE receptors, caused severe colitis in mice. Moreover, EP4-selective agonist (AE1-734) was also revealed to ameliorate severe dextran sodium sulfate-induced colitis in mice. We therefore examined the effects of 2 weeks intravenous EP4-selective agonist therapy for patients with mild to moderate ulcerative colitis.

Eligibility

Ages Eligible for Study:	20 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Clinical diagnosis of ulcerative colitis
Mild to moderate ulcerative colitis refractory to 5-aminosalicylates therapy.
20 years and above
Must obtain written informed consent

Exclusion Criteria:

Corticosteroids therapy within two weeks before enrollment
Immunosuppressive therapy within three months before enrollment
Leukocytapheresis therapy within one month before enrollment
Blood transfusion within two weeks before enrollment
Impaired renal function
Impaired hepatic function
Uncontrolled hypertension/hypotension
Uncontrolled arrhythmia
Impaired cardiac function
Cancer
Uncontrolled diabetes
Interstitial pneumonia
Glaucoma
History of colon resection
Infectious diseases needing medical treatments
Drug allergy
Pregnancy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00296556

Locations

Japan
Kyoto University, Graduate School of Medicine
Kyoto, Japan, 606-8501

Sponsors and Collaborators

Kyoto University, Graduate School of Medicine

National Institute of Biomedical Innovation

Investigators

Study Chair:	Shuh Narumiya, MD, PhD	Kyoto University, Graduate School of Medicine
Principal Investigator:	Tsutomu Chiba, MD, PhD	Kyoto University, Graduate School of Medicine

More Information

Publications:

Kabashima K, Saji T, Murata T, Nagamachi M, Matsuoka T, Segi E, Tsuboi K, Sugimoto Y, Kobayashi T, Miyachi Y, Ichikawa A, Narumiya S. The prostaglandin receptor EP4 suppresses colitis, mucosal damage and CD4 cell activation in the gut. J Clin Invest. 2002 Apr;109(7):883-93.

Morimoto K, Sugimoto Y, Katsuyama M, Oida H, Tsuboi K, Kishi K, Kinoshita Y, Negishi M, Chiba T, Narumiya S, Ichikawa A. Cellular localization of mRNAs for prostaglandin E receptor subtypes in mouse gastrointestinal tract. Am J Physiol. 1997 Mar;272(3 Pt 1):G681-7.

Responsible Party:	Kyoto University, Graduate School of Medicine ( Hiroshi Nakase / Associate Professor )
Study ID Numbers:	TRC05PG-II-1
Study First Received:	February 24, 2006
Last Updated:	April 27, 2009
ClinicalTrials.gov Identifier:	NCT00296556 History of Changes
Health Authority:	Japan: Ministry of Health, Labor and Welfare

Keywords provided by Kyoto University, Graduate School of Medicine:

Ulcerative colitis
EP4 agonist
PGE2

Additional relevant MeSH terms:

Pathologic Processes
Digestive System Diseases
Gastrointestinal Diseases
Ulcer
Colonic Diseases

Inflammatory Bowel Diseases
Colitis, Ulcerative
Intestinal Diseases
Gastroenteritis
Colitis

ClinicalTrials.gov processed this record on November 09, 2009