Clinical trial NCT05212792: Genomics and COVID-19 Vaccine Adverse Events
Official title: Genomics of COVID-19 Vaccine-induced Adverse Events (Guillain-Barré Syndrome [GBS], Vaccine-induced Immune Thrombotic Thrombocytopenia [VITT]/thrombosis with Thrombocytopenia Syndrome [TTS], and Myocarditis/pericarditis)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Vaccine Adverse Reaction
Keywords: Genomics
COVID-19 vaccine adverse event
Guillain-Barré syndrome (GBS)
Vaccine-induced Immune Thrombotic Thrombocytopenia (VITT)
Thrombosis with thrombocytopenia syndrome (TTS)
Myocarditis
Pericarditis
Lead sponsor: University of British Columbia
Sponsor class: OTHER
Collaborators: name: Centers for Disease Control and Prevention
First posted: 2022-01-28
Enrollment: 6325
Sex: ALL
Minimum age (years): 5
Maximum age (years): 99
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Any individual who received a COVID-19 vaccine.

A total of 825 adverse event cases (n=275 each for GBS, VITT/TTS, and myocarditis/pericarditis) and 5,500 vaccine-matched controls (n=2,750 each for mRNA and adenovirus vector COVID-19 vaccine platforms) will be recruited.

Brief summary: Vaccines routinely used are extremely safe; however, severe adverse events to vaccines do occur. As vaccination against COVID-19 has begun, adverse events to the vaccine, particularly Guillain-Barré syndrome (GBS), vaccine-induced immune thrombotic thrombocytopenia (VITT)/thrombosis with thrombocytopenia syndrome (TTS), and myocarditis/pericarditis, after COVID-19 vaccination have been reported worldwide.

Study hypothesis: there are genetic factors that contribute to increased risks of particular COVID-19 vaccine-induced adverse events.

The objective of the study is to determine if there are specific genetic factors strongly associated with each of the COVID-19 vaccine-induced adverse events (i.e., GBS, VITT/TTS, and myocarditis/pericarditis).

Detailed description: Purpose:

Reduce the risk of COVID-19 vaccine-induced adverse events (i.e., GBS, VITT/TTS, and myocarditis/pericarditis) through improved understanding of the biology underlying these severe adverse events and the genetic contribution to their cause

Research Design:

* Prospective case-control study designs will be performed to investigate the genetic associations of Guillain-Barré syndrome (GBS), vaccine-induced immune thrombotic thrombocytopenia (VITT)/thrombosis with thrombocytopenia syndrome (TTS), and myocarditis/pericarditis strongly associated (OR ≥ 3.0) with COVID-19 vaccination.
* Determined cases of specific COVID-19 vaccine-induced GBS, VITT/TTS, and myocarditis/pericarditis, and vaccinated controls without these adverse events will be included.
* Saliva DNA samples from eligible adverse event cases and vaccinated controls will be collected.
* Candidate gene and genome-wide association studies (GWAS) approaches will be conducted.
* Genomics analyses will be stratified by severity, age, sex, vaccine, and other critical covariates as determined by the GVDN Work Group for each adverse event and as adequately powered analyses allow.
* To complement GWAS, particularly in protein-coding regions, additional whole-exome sequencing (WES) will be performed on the most severe patients who are categorized as Brighton Collaboration Level One case of COVID-19 vaccine-induced adverse events to identify the most possible disease-causing mutations.

Eligibility criteria: Inclusion Criteria:

* Case: Any patient who received COVID-19 vaccines and developed GBS, VITT/TTS, or myocarditis/pericarditis after vaccination
* Control: Any participant who received COVID-19 vaccines and does not experience GBS, VITT/TTS, or myocarditis/pericarditis.

Exclusion Criteria:

* Individuals who have not received a COVID-19 vaccine
* Individuals who are unable to provide informed consent

Primary outcomes:
measure: Determine specific genetic factors associated with particular COVID-19 vaccine-induced Guillain-Barré syndrome (GBS), vaccine-induced immune thrombotic thrombocytopenia (VITT)/thrombosis with thrombocytopenia syndrome (TTS), and myocarditis/pericarditis
timeFrame: December 2025
Secondary outcomes:
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital Research Institute
state: British Columbia
Study officials:
affiliation: University of British Columbia
name: Bruce Carleton, PharmD
role: PRINCIPAL_INVESTIGATOR
References: