Clinical trial NCT04485598: Genetic Identification of Monogenic Disorders in Early-onset Stroke Using Targeted Next Generation Sequencing Panel
Official title: Genetic Identification of Monogenic Disorders in Early-onset Stroke Using Targeted Next Generation Sequencing Panel
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Stroke, Acute
Transient Ischemic Attack
Single-gene Disorders
Keywords: Stroke
Transient Ischemic Attack
Targeted sequencing panel
Early-onset
Lead sponsor: Beijing Tiantan Hospital
Sponsor class: OTHER
Collaborators: name: Beijing Municipal Science & Technology Commission
First posted: 2020-07-24
Enrollment: 502
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Acute ischemic stroke or Transient ischemic attack patients from participating centers over China that can be enrolled within 7 days of symptoms onset defined by the"last see normal"principle.Female or male aged ≥ 18 years and ≤ 45 years.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of patients with certain etiologic diagnosis established with targeted sequencing
timeFrame: day 0
Secondary outcomes:
measure: Obtained read depth according to number of pooled samples
timeFrame: day 0
measure: Percentage of patients with variant with unknown significance
timeFrame: day 0
measure: Clinical phenotype for each gene for which a causal mutation is identified by targeted sequencing panel
timeFrame: day 0
measure: Time of analysis of NGS raw data
timeFrame: 30 days
measure: Incidence of certain single-gene disorders in early-onset stroke patients
timeFrame: day 0
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tian Tan Hospital, Capital Medical University
state: Beijing
Study officials:
affiliation: Beijing Tian Tan Hospital, Capital Medical University, Beijing, China
name: Wei Li, M.D
role: PRINCIPAL_INVESTIGATOR
References: