Efficacy Study of T2 Versus AZA to Maintain Clinical and Endoscopic Remission in Postoperative Crohn's Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by Jinling Hospital, China
Sponsor:
Information provided by (Responsible Party):
Zhu Weiming, Jinling Hospital, China
ClinicalTrials.gov Identifier:
NCT01015391
First received: November 17, 2009
Last updated: June 1, 2013
Last verified: June 2013
  Purpose

The purpose of this study is to see whether T2 versus Azathioprine is able to maintain the clinical and endoscopic remission in subjects with Crohn's disease after surgery-induced remission.

The side effects related to T2 and AZA will also be monitored throughout the study.


Condition Intervention
Crohn's Disease
Drug: T2
Drug: Azathioprine

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Controlled, Open-label Study to Assess the Efficacy of T2 Versus Azathioprine for the Maintenance of Clinical and Endoscopic Remission in Subjects With Crohn's Disease After Surgical Resection

Resource links provided by NLM:


Further study details as provided by Jinling Hospital, China:

Primary Outcome Measures:
  • Clinical Remission: the proportion of patients with CDAI <150 at 26 and 52 weeks [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Endoscopic Remission: the proportion of patients with CDEIS <6 at 26 and 52 weeks [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The time till the clinical relapse of CD(the CDAI >150 or an increase of more than 70 points) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • The time till the histological recurrence(determined by biopsies and endoscopic findings) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Serum C-reactive protein concentration; Erythrocyte Sedimentation Rate [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • The proportion of patients experiencing adverse events [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 100
Study Start Date: November 2009
Estimated Study Completion Date: June 2013
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: T2 Drug: T2
1.5mg/kg/day, PO (per oral),three times a day: until progression or unacceptable toxicity develops
Active Comparator: AZA Drug: Azathioprine
2.5mg/kg, PO (per oral) one time a day:until progression or unacceptable toxicity develops the first month:1.5mg/kg,PO,one time a day the second month:2.0mg/kg,PO,one time a day since the third month:2.5mg/kg,PO,one time a day

Detailed Description:

Crohn's disease is characterized by inflammation and ulceration of the small intestine and colon. Patients commonly experience abdominal pain, diarrhea,malnutrition and malaise which result in decreased quality of life and an increased risk of chronic disability and unemployment. Surgical resection is required in approximately 70% of the patients at some time. However, recurrence of the disease after operation occurs in the majority of patients and is a serious limitation of surgical management. Patients' quality of life is often severely diminished. Currently available therapeutic options for the maintenance of remission in Crohn's disease are inadequate. A clear need exists for well-tolerated drugs that can reliably reduce the risk of a disease relapse.

AZA is classical immunomodulator,often applied to hematologic diseases and immune-related diseases,also the most commonly used drug in the maintenance of remission in Crohn's disease, it is indicated in steroid resistant or dependent patients, in those whose frequency of relapse is >1 per year, in patients after induction of remission with IFX, and in patients whose remission were induced by surgical resection. However, AZA may cause some adverse effects,the most serious adverse effect is leucopenia, which can develop suddenly and unpredictably, though it is rare (around 3%).

T2 is a chloroform/methanol extract Tripterygium wilfordii Hook F (TWHF), the traditional Chinese medicine,used in rheumatoid arthritis and nephritis. It has both immunomodulatory and anti-inflammatory activities.Our previous animal studies have revealed that the major component of T2, triptolide, could prevent the development of chronic colitis in interleukin-10 deficient mice. The phase I clinical trial in our institute also demonstrated that T2, or combined with enteral nutrition, is efficient for induction of remission in patients with active Crohn's disease.The common adverse effects of T2 are leucopenia,liver renal toxicity,oligospermia and amenorrhea.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects should have a definitive diagnosis of Crohn's disease, based on WHO criteria
  • Subjects having curative resection/ileocolonic anastomosis,pathologically diagnosed as Crohn's disease
  • Lesions located in ileum or ileocecal region
  • Males and females ≥ 18 years old, including women who are not pregnant or lactating at the time of enrollment.
  • Body weight between 40 and 100 kg, inclusive.
  • Subjects should have a CDAI score <150 at week 0
  • Able to swallow tablets
  • Are capable of providing written informed consent and obtained at the time of enrollment
  • Willing to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria:

  • Bacterial,viral or other microbial infection(including HIV)
  • any of the following medications taken within 12 weeks before surgery: cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, or other investigational drugs
  • any of ongoing therapy for Crohn's disease with: 5-ASA compounds, steroids, immune modifiers, systemic antibiotics, and tube feeding
  • Needing orally administered corticosteroids for the treatment of other diseases. Inhaled or dermatologic preparations are acceptable.
  • Previous or current use of infliximab.
  • current use of prescription doses or chronic/frequent use of NSAIDs
  • Treatment with narcotic pain medications. (Anti-diarrheal agents such as loperamide and diphenoxylate are permitted, providing that the dose is not increased during the study period.)
  • With an ileal or colonic stoma.
  • History of pancreatitis, except for subjects with a known but removed cause(such as gallstone pancreatitis)
  • WBC <3.0 x 109/L, hemoglobin <80 g/L, Platelets<50,000/mm3 at the time of enrollment (or within the previous 6 months, if known)
  • History of abnormal liver function tests, including AST or ALT >1.5 times upper limit of normal, alkaline phosphatase >2 times upper limit of normal, total bilirubin >2.5 mg/dL at screening (or within the previous 6 months, if known)
  • With short bowel syndrome (defined as requiring oral or parenteral supplemental or total nutrition to maintain stable body weight, or more than 100 cm of small bowel resected)
  • History of malignancy
  • Women who are pregnant or lactating at the time of enrollment, or who intend to be during the study period.
  • Participation in other clinical trial within the past 6 months
  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: NCT01015391

Contacts
Contact: Weiming Zhu, PhD,MD +86-25-80860137 juwiming@yahoo.com.cn

Locations
China, Jiangsu
General Surgery Institute,Jinling Hospital Recruiting
Nanjing, Jiangsu, China, 210000
Contact: Weiming Zhu, PhD,MD    +86-25-80860137    juwiming@yahoo.com.cn   
Principal Investigator: Weiming Zhu, PhD,MD         
Sponsors and Collaborators
Jinling Hospital, China
Investigators
Principal Investigator: Weiming Zhu, PhD,MD General Surgery Institute,Jinling Hospital,Nanjing,Jiangsu,China
  More Information

Publications:

Responsible Party: Zhu Weiming, vice director of General surgery institute, Jinling Hospital, China
ClinicalTrials.gov Identifier: NCT01015391     History of Changes
Other Study ID Numbers: TW2-001
Study First Received: November 17, 2009
Last Updated: June 1, 2013
Health Authority: China: Food and Drug Administration

Keywords provided by Jinling Hospital, China:
T2
AZA
remission
Crohn's disease

Additional relevant MeSH terms:
Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Azathioprine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on September 18, 2014