Monitoring of Azathioprine Metabolite Concentrations and Cytokine Levels in Neuromyelitis Optica Spectrum Disorder

June 8, 2023 updated by: Qingmeng Huang, First Affiliated Hospital of Guangxi Medical University

Background: The pathogenesis of NMOSD has been linked to the cytokines interleukins (IL) -6, NOD-, LRR-and pyrin domain-containing 3 (NLRP3) and IL-18 that contribute to development of inflammatory reactionsmay. Although azathioprine (AZA) is efficacious in preventing NMOSD recurrence, it may have adverse effects (AEs) maybe related to the plasma concentrations.

Objective: We would monitor the blood concentrations of AZA in NMOSD, and their relationship with cytokines, severity, efficacy, and safety range of the drug.

Methods: A total of 53 NMOSD patients were included in the study, which included 20 patients who had received AZA treatment within 1 month, and 16 patients who had received AZA treatment within 6 months, as well as 17 patients who had received AZA treatment at least 12 months. The patient's immunotherapy regimen was low-dose hormone combined with AZA. AZA was started at small doses and added every two weeks after no AEs, namely 50 mg qd for two weeks, 50mg bid for two weeks, and maintained at 50mg tid. The following clinical data were collected: gender, age, clinical symptoms, EDSS score, number of recurrences and AEs, etc. Healthy controls (HC) comprised 10 individuals. AZA metabolite concentrations 6-thioguaninenucleotides (6-TGN) and 6-methylmercaptopurine nucleotides (6-MMPN) were measured by High-performance liquid chromatography (HPLC). Levels of IL-6, NLRP3 and IL-18 were measured by Enzyme-linked immunosorbent assay (ELISA).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

A total of 53 NMOSD patients were recruited from Neurology Department of the First Affiliated Hospital of Guangxi Medical University.According to the duration of AZA treatment, 20 patients were divided into 1 month after AZA treatment, 16 patients in 6 months after AZA treatment and 17 patients over 12 months after AZA treatment. Clinical data of patients were collected, including: gender, age, time of first onset, time of medication, clinical symptoms, number of recurrence, EDSS score, serum and cerebrospinal fluid AQP 4-IgG titers, imaging results, rheumatic immunity-related autoimmune antibodies, comorbidities, related adverse drug reactions, etc. Ten healthy volunteers with physical examination in our hospital were selected as the healthy control (HC) group.Blood (5ml) was collected from peripheral veins of patients and healthy volunteers.

Study Type

Interventional

Enrollment (Actual)

63

Phase

  • Phase 4

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

  • China
    • Guangxi
      • Nanning, Guangxi, China, 530021
        • Qingmeng Huang

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

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

All patients with NMOSD met the international consensus diagnostic criteria for NMOSD published in 2015. Before medication, TPMT activity was normal.

Exclusion Criteria:

Patients with fever, infection, or patients with other autoimmune diseases, uncontrolled malignancies, and other chronic diseases were excluded.

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: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 1 month after AZA treatment
Before medication, TPMT activity was normal, and azathioprine was started at small doses and added every two weeks after no adverse effects, namely 50 mg qd for two weeks, 50mg bid for two weeks, and maintained at 50mg tid. Low-dose hormone therapy was administered to all patients simultaneously.Blood (5ml) was collected from peripheral veins in 1 month after AZA treatment.
Drug: Azathioprine
Before medication, TPMT activity was normal, and AZA was started at small doses and added every two weeks after no AEs, namely 50 mg qd for two weeks, 50mg bid for two weeks, and maintained at 50mg tid.
Other Names:
  • Azathioprine Tablets
Active Comparator: 6 months after AZA treatment
Before medication, TPMT activity was normal, and azathioprine was started at small doses and added every two weeks after no adverse effects, namely 50 mg qd for two weeks, 50mg bid for two weeks, and maintained at 50mg tid. Low-dose hormone therapy was administered to all patients simultaneously.Blood (5ml) was collected from peripheral veins in 6 months after AZA treatment.
Drug: Azathioprine
Before medication, TPMT activity was normal, and AZA was started at small doses and added every two weeks after no AEs, namely 50 mg qd for two weeks, 50mg bid for two weeks, and maintained at 50mg tid.
Other Names:
  • Azathioprine Tablets
Active Comparator: over 1 year after AZA treatment
Before medication, TPMT activity was normal, and azathioprine was started at small doses and added every two weeks after no adverse effects, namely 50 mg qd for two weeks, 50mg bid for two weeks, and maintained at 50mg tid. Low-dose hormone therapy was administered to all patients simultaneously.Blood (5ml) was collected from peripheral veins over 1 year after AZA treatment.
Drug: Azathioprine
Before medication, TPMT activity was normal, and AZA was started at small doses and added every two weeks after no AEs, namely 50 mg qd for two weeks, 50mg bid for two weeks, and maintained at 50mg tid.
Other Names:
  • Azathioprine Tablets
No Intervention: healthy control
Ten healthy volunteers with physical examination in our hospital were selected as the healthy control (HC) group. Serum samples from healthy controls were collected.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The concentrations of 6-TGN and 6-MMPN in NMOSD patients
Time Frame: 1 month
The mean 6-TGN concentrations and 6-MMPN concentrations in 1 month after AZA treatment were tested by HPLC
1 month
The concentrations of 6-TGN and 6-MMPN in NMOSD patients
Time Frame: 6 months
The mean 6-TGN concentrations and 6-MMPN concentrations in 6 months after AZA treatment were tested by HPLC.
6 months
The concentrations of 6-TGN and 6-MMPN in NMOSD patients
Time Frame: 12 months
The mean 6-TGN concentrations and 6-MMPN concentrations in over 12 months after AZA treatment were tested by HPLC.
12 months
Serum levels of IL-6, NLRP3 and IL-18 in NMOSD patients and HC
Time Frame: 1 month
The levels of IL-6, IL-18, and NLRP 3 inflammasome were measured in the enzyme-linked immunoassay kit.
1 month
Serum levels of IL-6, NLRP3 and IL-18 in NMOSD patients and HC
Time Frame: 6 months
The levels of IL-6, IL-18, and NLRP 3 inflammasome were measured in the enzyme-linked immunoassay kit.
6 months
Serum levels of IL-6, NLRP3 and IL-18 in NMOSD patients and HC
Time Frame: 12 months
The levels of IL-6, IL-18, and NLRP 3 inflammasome were measured in the enzyme-linked immunoassay kit.
12 months

Collaborators and Investigators

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

Sponsor

First Affiliated Hospital of Guangxi Medical University

Investigators

  • Study Director: Yulan Tang, First Affiliated Hospital of Guangxi Medical 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 (Actual)

January 1, 2020

Primary Completion (Actual)

December 31, 2022

Study Completion (Actual)

April 1, 2023

Study Registration Dates

First Submitted

May 22, 2023

First Submitted That Met QC Criteria

June 8, 2023

First Posted (Actual)

June 9, 2023

Study Record Updates

Last Update Posted (Actual)

June 9, 2023

Last Update Submitted That Met QC Criteria

June 8, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • qingmenghuang

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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.

Clinical Trials on NMO Spectrum Disorder

Clinical Trials on Azathioprine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Congo

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe