Thalidomide in Treating Crohn's Disease

Thalidomide in Inducing and Maintaining Remission of Crohn's Disease

Crohn's disease (CD) is a chronic gastrointestinal inflammatory disease characterized by relapse and progression. The incidence and prevalence of IBD are increasing in different regions around the world, indicating its emergence as a global disease. Though modern medical therapies including immunomodulators and biologic agents have revolutionized treatment of CD, the occurrence of steroids-dependence and resistance or intolerance to medical therapy is quite common. The limitation of present therapeutic management and the high expense of biologic agents leads to the treatment of CD become "refractoriness". The occurrence rate of steroids-dependence and resistance or intolerance to thiopurine therapy is quite high during the course of CD. Approximately 38% of cases required surgery within 10 years. Therefore, the management of such refractory CD remains a great therapeutic challenge for clinicians.

Thalidomide is an oral agent that has immunomodulatory, antiangiogenic and TNF(tumor necrosis factor)-a- suppressing effects. The potential role for thalidomide in the treatment of refractory paediatric and adult CD has been investigated in more and more small open-label studies and retrospective case series. Recently, a randomized controlled trial showed thalidomide improved clinical remission at 8 weeks of treatment and longer-term maintenance of remission in pediatric refractory CD. Gerich et al reported in a retrospective study that thalidomide improved long-term outcomes among 37 refractory CD adults followed up for a median of 58 months. However, the dose of thalidomide used in these studies ranged from 50mg/d to 150mg/d, and the occurrence rate of side effects reported variously but all quite high. The side effects related to the dose of thalidomide were the major concerns of using it in CD. Moreover, the effect of thalidomide on endoscopic response including mucosal healing which is a more objective and important outcome in CD was rarely reported. Therefore the aim of this study is to investigate the efficacy on clinical and endoscopic response and the adverse effects of using low-dose thalidomide in active adult CD patients.

Study Overview

• Status: Completed
• Conditions: Crohn's Disease
• Intervention / Treatment: Drug: Thalidomide

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • The First Affiliated Hospital of Sun Yat-Sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

A CDAI score greater than 150 at baseline was required for inclusion .(1) steroid-dependent: unable to reduce steroids below the equivalent of prednisone 10 mg/day (or budesonide below 3 mg/day) within 3 months of starting steroids, or who have a relapse within 3 months of stopping steroids.(2) thiopurines-non-responsive: active disease or clinical relapse despite administration of azathioprine (1.5-2 mg per kg per day) or 6-mercaptopurine (0.75-1.5 mg per kg per day) for 4 months. (3) thiopurines- intolerant: intolerance to or adverse events of thiopurines.

The exclusion criteria were (1) isolated L4 CD; (2) disease including symptomatic stenosis of intestine or abdominal abscess requiring immediate surgery; (3) Current or past history of malignancy or organ transplantation; (4) Serious infections within 3 months; (5) Previous history of neuropathy or symptoms of neuropathy or abnormal electromyography prior to thalidomide; (6) infliximab treatment in the previous 8 weeks; (7) progressive or uncontrolled renal, hepatic, hematological, pulmonary and cardiac disease and（8）ongoing pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Thalidomide; Thalidomide was administered at a daily dose of 50 mg to the patients. Dosage adjustment of thalidomide from 25mg daily to 100mg daily was tailored individually according to patients' tolerance to thalidomide. To minimize the sedative effect of thalidomide, the investigators recommended patients take a single dose of the study drug in the evening before bedtime.	Drug: Thalidomide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical remission	Clinical remission is defined as CDAI (Crohn's disease activity index) less than 150.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
clinical response and endoscopic efficacy	Clinical response was defined as a decrease in CDAI score of ≥100 points from baseline. Endoscopic efficacy was reassessed by ileocolonoscopy at week 24. Endoscopic outcome measures included endoscopic response (decrease in CDEIS score >5 points from baseline of CDEIS of 6 or more), complete remission (CDEIS score <3) and mucosal healing (no ulcer)response was defined as a decrease in CDAI score of ≥100 points from baseline. Endoscopic efficacy was reassessed by ileocolonoscopy at week 24. Endoscopic outcome measures included endoscopic response (decrease in CDEIS score >5 points from baseline of CDEIS of 6 or more), complete remission (CDEIS score <3) and mucosal healing (no ulcer)	24 weeks

Collaborators and Investigators

• Sponsor: First Affiliated Hospital, Sun Yat-Sen University

Publications and helpful links

General Publications

• Lazzerini M, Martelossi S, Magazzu G, Pellegrino S, Lucanto MC, Barabino A, Calvi A, Arrigo S, Lionetti P, Lorusso M, Mangiantini F, Fontana M, Zuin G, Palla G, Maggiore G, Bramuzzo M, Pellegrin MC, Maschio M, Villanacci V, Manenti S, Decorti G, De Iudicibus S, Paparazzo R, Montico M, Ventura A. Effect of thalidomide on clinical remission in children and adolescents with refractory Crohn disease: a randomized clinical trial. JAMA. 2013 Nov 27;310(20):2164-73. doi: 10.1001/jama.2013.280777.
• Gerich ME, Yoon JL, Targan SR, Ippoliti AF, Vasiliauskas EA. Long-term outcomes of thalidomide in refractory Crohn's disease. Aliment Pharmacol Ther. 2015 Mar;41(5):429-37. doi: 10.1111/apt.13057. Epub 2014 Dec 15.

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: May 20, 2015
• First Submitted That Met QC Criteria: July 15, 2015
• First Posted (Estimate): July 17, 2015

Study Record Updates

• Last Update Posted (Estimate): March 1, 2016
• Last Update Submitted That Met QC Criteria: February 29, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Thalidomide
• Other Study ID Numbers: IBD201501

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No