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

NCT ID: NCT01015391

Last Updated: 2013-06-04

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-11-30
• Study Completion Date: 2013-06-30

Brief Summary

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.

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.

Conditions

Crohn's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

T2

Group Type: EXPERIMENTAL

T2

Intervention Type: DRUG

1.5mg/kg/day, PO (per oral),three times a day: until progression or unacceptable toxicity develops

AZA

Group Type: ACTIVE_COMPARATOR

Azathioprine

Intervention Type: DRUG

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

Interventions

T2

1.5mg/kg/day, PO (per oral),three times a day: until progression or unacceptable toxicity develops

Intervention Type: 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

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jinling Hospital, China

OTHER

Sponsor Role: lead

Responsible Party

Zhu Weiming

vice director of General surgery institute

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Weiming Zhu, PhD,MD

Role: PRINCIPAL_INVESTIGATOR

General Surgery Institute,Jinling Hospital,Nanjing,Jiangsu,China

Locations

General Surgery Institute,Jinling Hospital

Nanjing, Jiangsu, China

Site Status: RECRUITING

Countries

China

Central Contacts

Weiming Zhu, PhD,MD

Role: CONTACT

juwiming@yahoo.com.cn

+86-25-80860137

Facility Contacts

Weiming Zhu, PhD,MD

Role: primary

juwiming@yahoo.com.cn

+86-25-80860137

References

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Peyrin-Biroulet L, Deltenre P, Ardizzone S, D'Haens G, Hanauer SB, Herfarth H, Lemann M, Colombel JF. Azathioprine and 6-mercaptopurine for the prevention of postoperative recurrence in Crohn's disease: a meta-analysis. Am J Gastroenterol. 2009 Aug;104(8):2089-96. doi: 10.1038/ajg.2009.301. Epub 2009 Jun 30.

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Ren J, Tao Q, Wang X, Wang Z, Li J. Efficacy of T2 in active Crohn's disease: a prospective study report. Dig Dis Sci. 2007 Aug;52(8):1790-7. doi: 10.1007/s10620-007-9747-y. Epub 2007 Apr 5.

Reference Type: BACKGROUND

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Wei X, Gong J, Zhu J, Niu L, Zhu W, Li N, Li J. Therapeutic effects of triptolide on interleukin-10 gene-deficient mice with colitis. Int Immunopharmacol. 2008 Dec 20;8(13-14):1808-12. doi: 10.1016/j.intimp.2008.08.019. Epub 2008 Sep 17.

Reference Type: BACKGROUND

PMID: 18804190 (View on PubMed)

Wei X, Gong J, Zhu J, Wang P, Li N, Zhu W, Li J. The suppressive effect of triptolide on chronic colitis and TNF-alpha/TNFR2 signal pathway in interleukin-10 deficient mice. Clin Immunol. 2008 Nov;129(2):211-8. doi: 10.1016/j.clim.2008.07.018. Epub 2008 Aug 30.

Reference Type: BACKGROUND

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Caprilli R, Gassull MA, Escher JC, Moser G, Munkholm P, Forbes A, Hommes DW, Lochs H, Angelucci E, Cocco A, Vucelic B, Hildebrand H, Kolacek S, Riis L, Lukas M, de Franchis R, Hamilton M, Jantschek G, Michetti P, O'Morain C, Anwar MM, Freitas JL, Mouzas IA, Baert F, Mitchell R, Hawkey CJ; European Crohn's and Colitis Organisation. European evidence based consensus on the diagnosis and management of Crohn's disease: special situations. Gut. 2006 Mar;55 Suppl 1(Suppl 1):i36-58. doi: 10.1136/gut.2005.081950c.

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Other Identifiers

TW2-001

Identifier Type: -

Identifier Source: org_study_id