Clinical trial NCT01060410: Exploration of Genotype Based Personalized Prescription of Cyclophosphamide in Systemic Lupus Erythematosus Treatment
Official title: Exploration of Genetic Polymorphisms Related to Individual Variations of Side Effects of Cyclophosphamide in Systemic Lupus Erythematosus Treatment
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Lupus Erythematosus, Systemic
Adverse Effects
Keywords: Myelosuppression
Infection
Nausea
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: First Affiliated Hospital, Sun Yat-Sen University
First posted: 2010-02-02
Enrollment: 222
Sex: ALL
Minimum age (years): 12
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: SLE patients receiving treatment with cyclophosphamide

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University
state: Guangdong
Study officials:
affiliation: Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
name: Min Huang, PhD.
role: STUDY_CHAIR
affiliation: Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
name: Xueding Wang, PhD.
role: STUDY_DIRECTOR
affiliation: Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
name: Wenying Shu, PhD.
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Rheumatology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
name: Xiuyan Yang, MD.
role: STUDY_DIRECTOR
affiliation: Department of Rheumatology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
name: Liuqin Liang, MD.
role: PRINCIPAL_INVESTIGATOR
References: