Exploration of Genotype Based Personalized Prescription of Cyclophosphamide in Systemic Lupus Erythematosus Treatment

Lupus Erythematosus, Systemic Clinical Trial

Official title:

Exploration of Genetic Polymorphisms Related to Individual Variations of Side Effects of Cyclophosphamide in Systemic Lupus Erythematosus Treatment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01060410
• Other study ID #: 30873124-CTX2008
• Status: Completed
• Phase: N/A
• First received: February 1, 2010
• Last updated: June 18, 2012
• Start date: May 2010
• Est. completion date: June 2012

Study information

• Verified date: June 2012
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: National Natural Science Foundation
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to investigate the relationship between the side effects of cyclophosphamide in the treatment of systemic lupus erythematosus (SLE) in Han Chinese and the genetic polymorphisms of drug metabolizing enzymes and pharmacokinetics of cyclophosphamide.

Description:

Cyclophosphamide is a widely applied agent in treatment of systemic lupus erythematosus. As an alkylating agent, cyclophosphamide is able to induce several side effects, including thinned hair, loss of appetite, nausea, vomiting, infection, myelosuppression, etc. However, the remarkable variability of the reactions to the drug -- the incidence of side effect or the outcome of the treatment -- has been observed among patients. Cyclophosphamide is a pro-drug, which require some enzymes in the liver to transform it into an active chemical to arouse alkylating function. And then it undergoes a series of detoxification steps catalyzed by the specific metabolic enzymes. This study is designed to explore the genetic variation among individuals in the key processes of the activation and elimination of cyclophosphamide in order to find out whether these genetic factors are associated to the side effects or efficacy. The further understanding into the factors concerning on the drug might imply possible solution to minimize the incidence of side effects in patients of systemic lupus erythematosus.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 222
• Est. completion date: June 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years to 80 Years

Eligibility

Inclusion Criteria:

1. The patients must have been diagnosed as SLE according to the American College of Rheumatology (ACR) criteria published in 1997.

2. The patients must sign the informed consent. And for the patients who are under 18 years old, both the signatures of their legal guardians and that of the patients are required on the written informed consent.

3. The patients are receiving the standard regimen of 0.2g cyclophosphamide given as intravenous injection once every two days.

Exclusion Criteria:

1. Pregnant women, women in breast-feeding period and the women who refuse to take contraception measures during treatment.

2. Patients with poor compliance.

3. Patients who are also diagnosed of cancer or who are receiving cyclophosphamide in treatment of cancer, or other anti-cancer therapy.

Study Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Adverse Effects
• Lupus Erythematosus, Systemic

Intervention

Genetic:
• Polymorphism Analysis
Analysis of genetic polymorphisms of the drug metabolic enzymes involving in the bio-activation and elimination of cyclophosphamide

Drug:
• Cyclophosphamide
intravenous injection, 0.2g, once every two days

Other:
• Pharmacokinetic analysis
laboratory analysis of concentration of cyclophosphamide and 4-OH-cyclophosphamide in plasma

Locations

Country	Name	City	State
China	Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University	Guangzhou	Guangdong

Sponsors (2)

Lead Sponsor	Collaborator
Sun Yat-sen University	First Affiliated Hospital, Sun Yat-Sen University

Country where clinical trial is conducted

China, 

External Links

•   Cyclophosphamide
•   Cytochrome P450
•   Help Me Understand Genetics
•   Systemic lupus erythematosus