Genetic Identification of Monogenic Disorders in Early-onset Stroke Using Targeted Next Generation Sequencing Panel

Completed

• Conditions: Single-gene Disorders; Transient Ischemic Attack; Stroke, Acute

• Registration Number: NCT04485598
• Lead Sponsor: Beijing Tiantan Hospital

Brief Summary

The study was designed as a multicenter multiracial prospective observational study of acute ischemic stroke and TIA patients across china. The purpose of this study is to determine the monogenic disorders incidence of Chinese early-onset stroke patients. We plan to consecutively enroll more than 500 patients with early-onset stroke(in the 18- to 45-year age range) admitted in stroke units within 7 days after symptoms onset in participating centers. These early-onset stroke patients are referred for targeted sequencing using 'cerebrovascular disease panel'. By analyzing the sequencing results, we intend to identify monogenic causes causing early-onset stroke and develop clinical algorithms that might assist the clinician in deciding in which early-onset stroke patients testing for monogenic causes of stroke.

Detailed Description

The study was designed as a multicenter multiracial prospective observational study of acute ischemic stroke and TIA patients across china. The purpose of this study is to determine the monogenic disorders incidence of Chinese early-onset stroke patients. We plan to consecutively enroll more than 500 patients with early-onset stroke(in the 18- to 45-year age range) admitted in stroke units within 7 days after symptoms onset in participating centers. Patients fulfilling all of the inclusion criteria and none of the exclusion criteria will be referred for targeted sequencing using 'cerebrovascular disease panel'. When one or multiple pathogenic or possible pathogenic exonic mutations are found, a Sanger Sequencing (SS) on somatic DNA from peripheral blood leukocyte of the index case and affected relatives will be performed for the screening of the same mutations. And the sporadic patient's mutations will be checked by SS in the unaffected family members. By analyzing the sequencing results, we intend to identify monogenic causes causing early-onset stroke and develop clinical algorithms that might assist the clinician in deciding in which early-onset stroke patients testing for monogenic causes of stroke.

Study Timeline

• Study Start: 2015-08-21
• Primary Completion: 2020-05-22
• Study Completion: 2020-05-22
• Status Verified: 2020-07
• Study First Submitted: 2020-07-21
• Study First Submitted QC: 2020-07-21
• Last Update Submitted: 2020-07-21
• Study First Posted: 2020-07-24
• Last Update Posted: 2020-07-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 502

Inclusion Criteria

• Provision of informed consent.
• Female or male aged ≥ 18 years and ≤ 45 years.
• Acute ischemic stroke or Transient ischemic attack((Neurological deficit attributed to focal brain ischemia, with resolution of the deficit within 24 hours of symptom onset) patients that can be enrolled within 7 days of symptoms onset defined by the"last see normal"principle.

Exclusion Criteria

• Asymptomatic brain infarction
• Neurological deficit due to causes other than ischemic stroke or TIA

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Percentage of patients with certain etiologic diagnosis established with targeted sequencing	day 0	Percentage of patients with certain etiologic diagnosis established with targeted sequencing

Secondary Outcome Measures

Name	Time	Method
Obtained read depth according to number of pooled samples	day 0	Obtained read depth according to number of pooled samples
Percentage of patients with variant with unknown significance	day 0	Percentage of patients with variant with unknown significance, needing supplementary analyses to prove its involvement in early-onset stroke
Time of analysis of NGS raw data	30 days	Time of analysis of NGS raw data
Incidence of certain single-gene disorders in early-onset stroke patients	day 0	Incidence of certain single-gene disorders in early-onset stroke patients
Clinical phenotype for each gene for which a causal mutation is identified by targeted sequencing panel	day 0	Clinical phenotype for each gene for which a causal mutation is identified by targeted sequencing panel

Trial Locations

Locations (1)

Beijing Tian Tan Hospital, Capital Medical University; 🇨🇳 Beijing, Beijing, China