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

NCT05896605 | Completed Phase 4 DMC

• 1 other identifier: qingmenghuang
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

NMO Spectrum Disorder; Azathioprine Adverse Reaction

Keywords

NMOSD, AZA, 6-TGN, 6-MMPN, IL-6, NLRP3, IL-18

Outcome Measures

Primary Outcomes (6)

• The concentrations of 6-TGN and 6-MMPN in NMOSD patients

  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

  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

  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

  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

  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

  The levels of IL-6, IL-18, and NLRP 3 inflammasome were measured in the enzyme-linked immunoassay kit.

  12 months

Study Arms (4)

1 month after AZA treatment

ACTIVE COMPARATOR

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

6 months after AZA treatment

ACTIVE COMPARATOR

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

over 1 year after AZA treatment

ACTIVE COMPARATOR

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

healthy control

NO INTERVENTION

Ten healthy volunteers with physical examination in our hospital were selected as the healthy control (HC) group. Serum samples from healthy controls were collected.

Interventions

Azathioprine DRUG

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.

Also known as: Azathioprine Tablets

1 month after AZA treatment; 6 months after AZA treatment; over 1 year after AZA treatment

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• First Affiliated Hospital of Guangxi Medical University: lead

Study Sites (1)

Qingmeng Huang

Nanning, Guangxi, 530021, China

Location

MeSH Terms

Conditions

Neuromyelitis Optica

Interventions

Azathioprine

Condition Hierarchy (Ancestors)

Myelitis, Transverse; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Optic Neuritis; Optic Nerve Diseases; Cranial Nerve Diseases; Demyelinating Diseases; Eye Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thionucleosides; Sulfur Compounds; Organic Chemicals; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Yulan Tang

  First Affiliated Hospital of Guangxi Medical University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Mrs.

Study Record Dates

• First Submitted: May 22, 2023
• First Posted: June 9, 2023
• Study Start: January 1, 2020
• Primary Completion: December 31, 2022
• Study Completion: April 1, 2023
• Last Updated: June 9, 2023

Record last verified: 2023-05

Locations

CN (1)