Genetics of COVID-19 Risks & Resilience in Bipolar Disorder

Covid19 Clinical Trial

— BIPCOVID  

Official title:

Genetics of COVID-19 Risks & Resilience in Bipolar Disorder as Subproject of BIPGEN (Genetic Changes in Bipolar Disorder)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04972708
• Other study ID #: 23-199 ex 10/11
• Status: Recruiting
• Start date: July 1, 2021
• Est. completion date: September 30, 2024

Study information

• Verified date: September 2021
• Source: Medical University of Graz
• Contact: Eva Reininghaus, MD, PhD, MBA
• Phone: +43 316 385 80968
• Email: eva.reininghaus[@]medunigraz.at
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

BIPGEN is a cross-sectional study on the genetics of bipolar disorder. As a subproject of BIPGEN, BIP-COVID is a cross-sectional genetics study about risks & resilience in the COVID-19 (Coronavirus disease) pandemic in bipolar disorder (BD) and healthy controls at the Medical University of Graz. Study participants with BD and controls from the well-established BIPLONG and BIPGEN studies will undergo a special BIP-COVID visit, which will include a COVID-19 specific online Lime survey about the psychological burden in the COVID-19 crisis, a COVID-19 antibody test (IgM and IgG), inflammation markers and isolation of DNA from fasting blood. Genotyping of DNA will be done with the GSA V.3 array. Genetic analyses (Polygenic Risk Scores of I. Stress or Major Depression and II. COVID-19 infection established with the programs PLINK, PRSice and R) will be used to analyze the genetic mechanisms of COVID-19 pandemic associated psychological symptoms and COVID-19 infection risk. Systems biology methods will be used to depict protective pathways against COVID-19 infection (e.g. Lithium pathways) and against COVID-19 associated psychiatric symptoms.

Description:

Methods: BIPGEN is a cross-sectional study on the genetics of bipolar disorder (BD). BIPGEN includes a personality questionnaire (TEMPS-A). DNA is isolated in the BIPGEN study from fasting blood with the QUIASYMPHONY robot from study participants with Bipolar Disorder (diagnosis according to DSM-IV) and healthy controls. The DNA is then genotyped with classic genotyping arrays (GWAS array). The aim of BIPGEN is to associate genetic variants (single-nucleotide-polymorphisms/ SNPs or copy-number-variations/CNVs) with bipolar affective disorder.

A subproject of BIPGEN is the BIP-COVID project, which is a cross-sectional genetics study about risks & resilience in the COVID-19 pandemic in BD and healthy controls at the Medical University of Graz. Study participants with BD and controls from the well-established BIPLONG and BIPGEN studies will undergo a special BIP-COVID visit, which will include a COVID-19 specific online Lime survey about the psychological burden in the COVID-19 crisis, a COVID-19 antibody test (IgM and IgG), inflammation markers and isolation of DNA from fasting blood. Genotyping of DNA will be done with the GSA V.3 array. Genetic analyses (Polygenic Risk Scores of I. Stress or Major Depression and II. COVID-19 infection established with the programs PLINK, PRSice and R) will be used to analyze the genetic mechanisms of COVID-19 pandemic associated psychological symptoms and COVID-19 infection risk. Systems biology methods will be used to depict protective pathways against COVID-19 infection (e.g. Lithium pathways) and against COVID-19 associated psychiatric symptoms

Aim:

1. We aim at analyzing the neuropsychological and genetic underpinning of COVID-19 associatedreactive psychiatric symptoms in BD and in healthy controls.

2. We aim at analyzing genetic predictors of COVID-19 infection in BD and in controls.

3. We aim at analyzing the protective effects of the GSK-3β inhibitor lithium against COVID-19 infection.

Intervention: Cross-sectional genetics study

Key inclusion and exclusion criteria: Inclusion criteria are written consent after previous written and verbal information, diagnosis of BD according to DSM-IV and age between 18 and 75 years. Exclusion criteria include acute suicidality, lack of consent, severe active drug dependence (i.e., alcohol, benzodiazepines, morphine), other currently active severe mental / cerebral organic disease (e.g. epilepsy, brain tumor), severe skull-brain trauma / brain surgery in the past, known florid tumor disease, congenital / infantile mental retardation, dementia (from Mini-Mental State Examination (MMSE) 20), severe florid autoimmune diseases or current immunosuppression (e.g., lupus erythematosus, HIV (human immunodeficiency virus), multiple sclerosis), cardiac, renal and pulmonary disorders or PTSD (post-traumatic stress disorder) or anxiety.

Healthy controls do not have a history of mental disorder and do not have first- or second-degree relatives with psychiatric disorders.

Primary and secondary endpoint(s) of the BIPCOVID project:

The primary endpoint is PRS of stress, the secondary endpoint is PRS of COVID-19 risk.

Sample size, statistical analyses, power calculation: The program G*Power (Version 3.1) was used for the calculation of the number of cases. Linear bivariate regression analyses for two groups (BD and control cohort) will be calculated with the results from psychological/psychiatric inventories as predictors (e.g. Pittsburgh Sleep Quality Index, Mediterranean Diet Score, Resilience Scale) and the three PRS as criterion. G*Power calculates for a linear bivariate regression, with a Δ slope of 0.03, α = .05 and a power of 95 % a total sample size of 364 persons.

Trial duration of BIPCOVID: 3 years.

Participating centers: The BIP-COVID sample will be recruited as monocentric study at the special outpatient department for Bipolar Disorders (managed by Univ.Prof. Eva Reininghaus) at the Department of Psychiatry and Psychotherapeutic Medicine at the Medical University of Graz, Austria. Psychiatric genetics and bioinformatics experts from the University of Basel, the University of Marburg, the University of Bonn, the Karolinska Institutet & Medical University of Vienna & CAMH Toronto will supervise the KLIF-funded doctoral student and will support the state-of-the-art bioinformatics analyses.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: September 30, 2024
• Est. primary completion date: September 1, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Inclusion criteria are written consent after previous written and verbal information, diagnosis of BD according to DSM-IV and age between 18 and 75 years.

Exclusion Criteria:

Exclusion criteria include

• acute suicidality

• lack of consent

• severe active drug dependence (i.e., alcohol, benzodiazepines, morphine)

• other currently active severe mental / cerebral organic disease (e.g. epilepsy, brain tumor),

• severe skull-brain trauma / brain surgery in the past,

• known florid tumor disease,

• congenital / infantile mental retardation,

• dementia (from MMSE 20),

• severe florid autoimmune diseases or current immunosuppression (e.g., lupus erythematosus, HIV, multiple sclerosis),

• cardiac, renal and pulmonary disorders or PTSD or anxiety

• Healthy controls do not have a history of mental disorder and do not have first- or second-degree relatives with psychiatric disorders.

Related Conditions & MeSH terms

• Bipolar Disorder
• Covid19
• Disease
• Stress

Intervention

Genetic:
• Cross-sectional genetics study
Cross-sectional genetics study

Locations

Country	Name	City	State
Austria	Medical University Graz	Graz	Styria

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Graz

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PRS of stress or depression	genetic sum score for depression (polygenic risk score)- the higher the score, the higher the risk	3 Years
Primary	PRS of COVID-19 infection	genetic sum score for COVID-19 infection (polygenic risk score)- the higher the score, the higher the risk	3 Years