A Prospective Study of Cyclophosphamide in Systemic Lupus Erythematosus Treatment (SLE)

August 27, 2014 updated by: Lingyan Chen, Sun Yat-sen University

Prospective Study Based on Genetic Polymorphisms Related to Individual Variations of Side Effects of Cyclophosphamide in Systemic Lupus Erythematosus Treatment

The purpose of this study is to compare the genotype-based personal prescription of cyclophosphamide with the traditional prescription.

Study Overview

Status

Completed

Intervention / Treatment

Detailed Description

Cyclophosphamide (CPA) has been one of the most successful therapies for severe Systemic lupus erythematosus (SLE). However, cyclophosphamide can cause severe side effects, including bone marrow suppression, infection, gastrointestinal reaction, hemorrhagic cystitis, and the etc. Significant variation in efficacy and toxicity of CPA has been observed. Since the development of applicable therapeutic drug monitoring (TDM) of cyclophosphamide has been reported, it will help to improve the efficacy and reduce toxicities in SLE treatment. However, the TDM is a passive strategy which usually lags behind the appearance of toxicities. Therefore,it is especially crucial to give individuals genotype-based personal prescription of cyclophosphamide in order to gain the most effective therapies. Thus, the purpose of this study is to compare the genotype-based personal prescription of cyclophosphamide with the traditional prescription, in order to verify the efficacy of the genotype-based personal prescription.

Study Type

Interventional

Enrollment (Actual)

92

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Guangdong
      • Guangzhou, Guangdong, China, 510006
        • School of Pharmaceutical Sciences Sun Yat-sen University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years to 60 years (Child, Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • The American College of Rheumatology established eleven criteria in 1982,which were revised in 1997 as a classificatory instrument to operationalise the definition of SLE in clinical trials.

    1. Malar rash (rash on cheeks).
    2. Discoid rash (red, scaly patches on skin that cause scarring).
    3. Serositis: Pleurisy (inflammation of the membrane around the lungs) or pericarditis (inflammation of the membrane around the heart).
    4. Oral ulcers (includes oral or nasopharyngeal ulcers).
    5. Arthritis: nonerosive arthritis of two or more peripheral joints, with tenderness, swelling, or effusion.
    6. Photosensitivity (exposure to ultraviolet light causes rash, or other symptoms of SLE flareups).
    7. Blood-hematologic disorder-hemolytic anemia (low red blood cell count) or leukopenia (white blood cell count<4000/µl), lymphopenia (<1500/µl) or thrombocytopenia (<100000/µl) in the absence of offending drug. Hypocomplementemia is also seen, due to either consumption of C3 and C4 by immune complex-induced inflammation or to congenitally complement deficiency, which may predispose to SLE.
    8. Renal disorder: More than 0.5 g per day protein in urine or cellular casts seen in urine under a microscope.
    9. Antinuclear antibody test positive.
    10. Immunologic disorder: Positive anti-Smith, anti-ds DNA, antiphospholipid antibody, and/or false positive serological test for syphilis. Presence of anti-ss DNA in 70% of cases (though also positive with rheumatic disease and healthy persons).
    11. Neurologic disorder: Seizures or psychosis. For the purpose of identifying patients for clinical studies, a person has SLE if any 4 out of 11 symptoms are present simultaneously or serially on two separate occasions. In the meantime, the case has one of the following conditions or more;
    1. HIV (-);
    2. Signed the informed consent;
    3. Taking contraceptive measures during treatment period.

Exclusion Criteria:

  • Poor compliance;
  • With lupus mental damage complication, occurrence of epilepsy or unable to express subjective symptoms during the observation period.
  • Taking drugs that affect cytochrome P450 2B6, cytochrome P450 3A4 and cytochrome P450 2C19, except corticosteroids.
  • Abnormal liver function.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Control Group
The cases in control group received traditional therapy that the initial dose of cyclophosphamide (CPA) was 0.2-0.6g/week injection according to clinical experience.
Experimental: Experimental Group
Genetic: Genotype Detection To Genotype cases in the experimental group and divide them into three groups, including extensive metaboliser (EM), intermediate metaboliser (IM) and poor metaboliser (PM),with initial dose of CPA as 0.2g, 0.4g and 0.6g per week by injection, respectively.
To Genotype cases in the experimental group and divide them into three groups, including extensive metaboliser (EM), intermediate metaboliser (IM) and poor metaboliser (PM).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse Reaction (Leucopenia)
Time Frame: one month
The count of white cells < 4.0 × 10ˆ9/L in SLE patient who received CPA medication was considered as CPA-induced leucopenia.
one month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse Reaction ( Infection )
Time Frame: one month
Flu-like symptoms, Upper respiratory tract infection,and the etc.
one month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Chair: Huang Min, PhD, Sun Yat-sen University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2012

Primary Completion (Actual)

December 1, 2013

Study Completion (Actual)

March 1, 2014

Study Registration Dates

First Submitted

September 17, 2012

First Submitted That Met QC Criteria

September 20, 2012

First Posted (Estimate)

September 21, 2012

Study Record Updates

Last Update Posted (Estimate)

September 8, 2014

Last Update Submitted That Met QC Criteria

August 27, 2014

Last Verified

August 1, 2014

More Information

Terms related to this study

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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