Genetic Study of Antithyroid Drugs Associated Agranulocytosis

Agranulocytosis Clinical Trial

Official title:

Genetic Study of Antithyroid Drugs Associated Agranulocytosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01977963
• Other study ID #: 201112083RID
• Status: Recruiting
• Phase: N/A
• First received: October 31, 2013
• Last updated: November 6, 2013
• Start date: April 2012

Study information

• Verified date: October 2013
• Source: National Taiwan University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Taiwan: Department of Health
• Study type: Observational

Clinical Trial Summary

Thionamides, the antithyroid drugs, have been widely used to treat hyperthyroidism1. Side effects are found in 1% - 5% of the patients1. One of the most serious side effect is agranulocytosis, which occurs in 0.1% - 0.3 % of the patients1. This might lead to severe infection and sometimes mortality. The underlying mechanism is unclear. An immune phenomenon may be involved because the antigranulocyte antibodies or lymphocyte sensitized to antithyroid drugs are found in these patients6,7. The recognition of major histocompatibility complex class II peptide complexes by T lymphocytes is central to the development of immune response. According to a report in 1996, the HLA DRB1*08032 allele is strongly associated with susceptibility to methimazole-induced agranulocytosis20.

Recently, there are new techniques for genetics study. We aimed to identify the associated genetic change of the agranulocytosis side effect of antithyroid drugs. First, we will look at the classical human Leukocyte Antigen (HLA) loci, such as HLA-A, -B, -C, -DR, -DQ and -DP. If no significant change is found in the above genes, we will consider whole exon sequencing with next-generation sequencing, Statistic analysis will include appropriate linkage analysis, association study, variation data analysis, pathway analysis. If we can identify the genetic change and perform genetic examinations before prescription, we can avoid the happening of severe side effects.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. primary completion date: January 2022
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 85 Years

Eligibility

Inclusion Criteria:

• patients with absolute neutrophil count lower than 500/mm3 caused by anti-thyroid drugs

Exclusion Criteria:

• Patients who is younger than 20 years old or older than 85 years old

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Agranulocytosis

Locations

Country	Name	City	State
Taiwan	National Taiwan University Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
National Taiwan University Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with anti-thyroid drug related agranulocytosis	The investigators review the chart to see if the patients had anti-thyroid drug related agranulocytosis	within 2 month after taking the drug	No