The Protein Disrupted in Schizophrenia 1 (DISC1) as a Novel Biomarker for Cardiac Disease

NCT06304233 | Active Not Recruiting DMC

• 1 other identifier: 606103
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 2

Brief Summary

To study the association between DISC1 RNA expression levels and cardiac function in patients with schizophrenia.

Conditions

Heart Diseases; Heart; Functional Disturbance; Schizophrenia

Keywords

Disrupted in Schizophrenia 1; DISC1; Cardiac Biomarker

Outcome Measures

Primary Outcomes (34)

• Left Ventricular Ejection Fraction (LVEF) measured by 2D Echocardiography

  Left ventricular ejection fraction, LVEF will be reported in percentage (%) and obtained using Simpson's biplane method from 2D echocardiography.

  Baseline

• Left Ventricular Ejection Fraction (LVEF) measured by 3D Echocardiography

  Left ventricular ejection fraction, LVEF will be reported in percentage (%) and obtained using 3D echocardiography

  Baseline

• DISC1 mRNA quantification

  Measured from blood samples and reported as fold change

  Baseline

• Levels of high sensitive-CRP

  Levels of HS-CRP mg/L

  Baseline

• Levels of CK-MB

  Levels of CK-MB is reported in µg/L

  Baseline

• Levels of Troponin T

  Levels of Troponin T is reported in ng/L

  Baseline

• Levels of Troponin I

  Levels of Troponin I is reported in ng/L

  Baseline

• Normalized Left Ventricular End-Diastolic Volume (LV EDV), echocardiographic parameter

  LV EDV in milliliters (mL) will be normalized against body surface area (BSA) in m\^2 to report LV EDV normalized by BSA in mL/m\^2.

  Baseline

• Normalized Right Ventricular End-Diastolic Volume (RV EDV), echocardiographic parameter

  RV EDV in mL will be normalized against body surface area (BSA) in m\^2 to report RV EDV normalized by BSA in mL/m\^2.

  Baseline

• Normalized left Ventricular End-Systolic Volume (LV ESV), echocardiographic parameter

  LV ESV in mL will be normalized against body surface area (BSA) in m\^2 to report LV ESV normalized by BSA in mL/m\^2.

  Baseline

• Normalized Right Ventricular End-Systolic Volume (RV ESV), echocardiographic parameter

  RV ESV in mL will be normalized against body surface area (BSA) in m\^2 to report RV ESV normalized by BSA in mL/m\^2.

  Baseline

• Left ventricular mass measured by echocardiography

  Left ventricular mass in grams (g) will be normalized against BSA in m\^2 and reported as g/m \^2

  Baseline

• Left ventricular septal thickness, left ventricular posterior wall thickness and right ventricular wall thickness measured by echocardiography

  Left ventricular septal thickness, left ventricular posterior wall thickness and right ventricular wall thickness will be reported in centimeters (cm)

  Baseline

• Fractional shortening measured by echocardiography

  Fractional shortening will be reported as a percentage (%)

  Baseline

• Global longitudinal strain (GLS), echocardiographic parameter

  GLS(%) = (MLs - MLd)/MLd, where MLs is myocardial length at end-systole and MLd is the myocardial length at end-diastole. GLS will be reported in precentage (%)

  Baseline

• TAPSE echocardiographic parameter of right ventricular longitudinal systolic function

  TAPSE will be reported in millimeters (mm)

  baseline

• Echocardiographic parameter MPI, Myocardial performance index

  MPI is a unitless index derived from the sum of the isovolumic relaxation time (IVRT) and the isovolumic contraction time (IVCT) in milliseconds (ms) divided by the ejection time interval in (ms).

  Baseline

• Echocardiographic parameter Mitral E/A ratio

  Mitral E/A ratio is derived from the ratio of the E wave velocity to the A wave velocity

  Baseline

• Echocardiography parameter of peak E velocity

  peak E velocity is reported in cm/s

  Baseline

• Echocardiography parameter of E wave deceleration time

  E wave deceleration time is reported in milliseconds (ms)

  Baseline

• Echocardiography parameter of ratio of E/e'

  The E/e' ratio is derived from the E wave velocity to the e' velocity

  Baseline

• Echocardiographic parameters septal e' and lateral e' velocities

  Septal e' and lateral e' velocities are reported as cm/s

  Baseline

• Echocardiographic parameter LAVI, left atrial volume indexed

  LAVI is reported in mL/m\^2 and is the volume (mL) of the left atrium indexed against the BSA in m\^2.

  Baseline

• Echocardiographic parameter TRpV, Tricuspid Regurgitation peak Velocity

  TRpV is reported in m/s

  Baseline

• Echocardiographic parameter, S wave velocity

  S wave velocity is the peak systolic velocity of the tricuspid annulus and is reported in cm/s

  Baseline

• Echocardiographic parameter, Indexed LV and RV stroke volumes

  Indexed LV stroke volume and Indexed RV stroke volume will be reported in mL/m\^2 by by indexing the volumes (mL) to BSA (m\^2)

  Baseline

• Levels of NT-proBNP

  Levels of NT-proBNP from blood samples will be reported in ng/L

  Baseline

• Levels of IGF1

  Levels of IGF1 from blood samples will be reported in nmol/L

  Baseline

• Levels of ANP

  Levels of ANP from blood samples will be reported in pg/mL

  Baseline

• Levels of BDNF, brain derived neurotrophic factor

  Levels of BDNF from blood samples will be reported in ng/mL

  Baseline

• Levels of Tumor Necrosis Factor alpha

  Levels of Tumor Necrosis Factor alpha from blood samples will be reported in pg/mL

  Baseline

• Levels of Transforming Growth Factor Beta

  Levels of Transforming Growth Factor Beta from blood samples will be reported in ng/mL

  Baseline

• Levels of cardiac Myosin-Binding Protein C

  Levels of cardiac Myosin-Binding Protein C from blood samples will be reported in ng/L

  Baseline

• Interleukin levels

  Interleukin levels from blood sample will be reported as pg/mL

  Baseline

Secondary Outcomes (24)

• native T1 time, cardiac MRI

  Baseline

• Indexed LV and RV end-diastolic, end-systolic and stroke volumes, cardiac MRI

  Baseline

• Indexed LV mass, cardiac MRI

  Baseline

• LV Ejection Fraction, cardiac MRI

  Baseline

• ECG corrected QT interval

  Baseline

Other Outcomes (17)

• Alcohol intake at baseline using The Alcohol Use Disorders Identification Test Consumption (AUDIT-C) questionnaire

  Baseline

• Average length of inpatient stay for schizophrenia related admissions

  Baseline

• Need of Care based on number of total hospital admission for schizophrenia

  Baseline

Study Arms (2)

Diagnosed with Schizophrenia

Patients with a ICD-10 diagnosis of Schizophrenia will undergo investigations to assess cardiac function, cardiovascular disease risk factors and DISC1 mRNA expression. Participants eligible for MRI will be invited to undergo cardiac MRI in addition to echocardiography.

Diagnostic Test: Echocardiography; Diagnostic Test: Cardiac Magnetic Resonance Imaging; Diagnostic Test: Electrocardiography; Other: Blood sampling

No mental health diagnosis

Participants without a mental health diagnosis will be randomly selected from an existing population registered in the HUNT data and biobank for whom, echocardiographic data and biological samples are available.Those enrolled as controls will be invited to participate in the cardiac MRI portion of the study.

Diagnostic Test: Echocardiography; Diagnostic Test: Cardiac Magnetic Resonance Imaging; Diagnostic Test: Electrocardiography; Other: Blood sampling

Interventions

Echocardiography DIAGNOSTIC_TEST

ultrasound assessment of heart structure, volume and function

Also known as: Echo

Diagnosed with Schizophrenia; No mental health diagnosis

Cardiac Magnetic Resonance Imaging DIAGNOSTIC_TEST

MRI assessment of heart structure, volume, function and tissue characteristics

Also known as: Cardiac MRI, CMRI

Diagnosed with Schizophrenia; No mental health diagnosis

Electrocardiography DIAGNOSTIC_TEST

Assessment of cardiac rhythm and electrical activity

Also known as: Holter, ECG

Diagnosed with Schizophrenia; No mental health diagnosis

Blood sampling OTHER

To measure DISC1 mRNA expression and other potential biomarkers

Diagnosed with Schizophrenia; No mental health diagnosis

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The cohort with schizophrenia will be recruited from outpatient and inpatient population from a single centre. The cohort without mental health diagnosis will be selected from an existing population registered in the HUNT data and biobank and be matched for age (± 2 years) and sex of the patients.

You may qualify if:

• Patients with ICD-10 schizophrenia, schizotypal or delusional disorders (F20 to F29)
• Both inpatient and outpatient
• Capable of giving informed consent

You may not qualify if:

• Current or previous diagnosis of cancer
• Current or previous treatment with chemotherapy
• Current pregnancy
• Mothers less than 6 months post-partum

Sponsors & Collaborators

• Norwegian University of Science and Technology: lead
• St. Olavs Hospital: collaborator

Study Sites (2)

Norwegian University of Science and Technology

Trondheim, Norway

Location

St Olavs Hospital, Trondheim University Hospital

Trondheim, Norway

Location

Biospecimen

Retention: SAMPLES WITH DNA

Plasma, serum, whole blood, peripheral blood mononuclear cells

MeSH Terms

Conditions

Heart Diseases; Schizophrenia

Interventions

Echocardiography; Caves; Electrocardiography; Electrocardiography, Ambulatory; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Cardiovascular Diseases; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cardiac Imaging Techniques; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Ultrasonography; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Geological Phenomena; Physical Phenomena; Environment; Ecological and Environmental Phenomena; Biological Phenomena; Environment and Public Health; Electrodiagnosis; Monitoring, Ambulatory; Monitoring, Physiologic; Specimen Handling; Clinical Laboratory Techniques; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Morten A Høydal, PhD

  Norwegian University of Science and Technology

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2023
• First Posted: March 12, 2024
• Study Start: December 13, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): June 1, 2038
• Last Updated: June 22, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: During the whole project period up to 15 years.
• Access Criteria: For cooperative research and publication within Norway, the EU and the US, for purposes inline with those in the Study protocol.

Locations

NO (2)