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

Primary Purpose

Crohn's Disease

Status

Unknown status

Phase

Not Applicable

Locations

China

Study Type

Interventional

Intervention

Azathioprine

About this trial

This is an interventional treatment trial for Crohn's Disease focused on measuring T2, AZA, remission, Crohn's disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

General Surgery Institute,Jinling HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

AZA

Arm Description

Outcomes

Primary Outcome Measures

Clinical Remission: the proportion of patients with CDAI <150 at 26 and 52 weeks

Endoscopic Remission: the proportion of patients with CDEIS <6 at 26 and 52 weeks

Secondary Outcome Measures

The time till the clinical relapse of CD(the CDAI >150 or an increase of more than 70 points)

The time till the histological recurrence(determined by biopsies and endoscopic findings)

Serum C-reactive protein concentration; Erythrocyte Sedimentation Rate

The proportion of patients experiencing adverse events

Full Information

NCT ID

NCT01015391

First Posted

November 17, 2009

Last Updated

June 1, 2013

Sponsor

Jinling Hospital, China

1. Study Identification

Unique Protocol Identification Number

NCT01015391

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2013

Overall Recruitment Status

Unknown status

Study Start Date

November 2009 (undefined)

Primary Completion Date

June 2013 (Anticipated)

Study Completion Date

June 2013 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Jinling Hospital, China

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Crohn's Disease

Keywords

T2, AZA, remission, Crohn's disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Title

AZA

Arm Type

Active Comparator

Intervention Type

Drug

Intervention Name(s)

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Azathioprine

Intervention Description

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

Primary Outcome Measure Information:

Title

Clinical Remission: the proportion of patients with CDAI <150 at 26 and 52 weeks

Time Frame

52 weeks

Title

Endoscopic Remission: the proportion of patients with CDEIS <6 at 26 and 52 weeks

Time Frame

52 weeks

Secondary Outcome Measure Information:

Title

The time till the clinical relapse of CD(the CDAI >150 or an increase of more than 70 points)

Time Frame

52 weeks

Title

The time till the histological recurrence(determined by biopsies and endoscopic findings)

Time Frame

52 weeks

Title

Serum C-reactive protein concentration; Erythrocyte Sedimentation Rate

Time Frame

52 weeks

Title

The proportion of patients experiencing adverse events

Time Frame

52 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Weiming Zhu, PhD,MD

Phone

+86-25-80860137

juwiming@yahoo.com.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Weiming Zhu, PhD,MD

Organizational Affiliation

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

Official's Role

Principal Investigator

Facility Information:

Facility Name

General Surgery Institute,Jinling Hospital

City

Nanjing

State/Province

Jiangsu

ZIP/Postal Code

210000

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Weiming Zhu, PhD,MD

Phone

+86-25-80860137

juwiming@yahoo.com.cn

First Name & Middle Initial & Last Name & Degree

Weiming Zhu, PhD,MD

12. IPD Sharing Statement

Citations:

PubMed Identifier

15362027

Citation

Hanauer SB, Korelitz BI, Rutgeerts P, Peppercorn MA, Thisted RA, Cohen RD, Present DH. Postoperative maintenance of Crohn's disease remission with 6-mercaptopurine, mesalamine, or placebo: a 2-year trial. Gastroenterology. 2004 Sep;127(3):723-9. doi: 10.1053/j.gastro.2004.06.002.

Results Reference

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PubMed Identifier

18799369

Citation

Almer SH, Hjortswang H, Hindorf U. 6-Thioguanine therapy in Crohn's disease--observational data in Swedish patients. Dig Liver Dis. 2009 Mar;41(3):194-200. doi: 10.1016/j.dld.2008.07.314. Epub 2008 Sep 16.

Results Reference

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PubMed Identifier

19687490

Citation

Goldbach-Mansky R, Wilson M, Fleischmann R, Olsen N, Silverfield J, Kempf P, Kivitz A, Sherrer Y, Pucino F, Csako G, Costello R, Pham TH, Snyder C, van der Heijde D, Tao X, Wesley R, Lipsky PE. Comparison of Tripterygium wilfordii Hook F versus sulfasalazine in the treatment of rheumatoid arthritis: a randomized trial. Ann Intern Med. 2009 Aug 18;151(4):229-40, W49-51. doi: 10.7326/0003-4819-151-4-200908180-00005.

Results Reference

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PubMed Identifier

19568226

Citation

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.

Results Reference

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PubMed Identifier

17410440

Citation

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.

Results Reference

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PubMed Identifier

18804190

Citation

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.

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PubMed Identifier

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Citation

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.

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Citation

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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Citation

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Citation

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Results Reference

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

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