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

Recruiting
Conditions
Schizophrenia
Heart Diseases
Heart; Functional Disturbance
Interventions
Diagnostic Test: Echocardiography
Diagnostic Test: Cardiac Magnetic Resonance Imaging
Diagnostic Test: Electrocardiography
Other: Blood sampling
Registration Number
NCT06304233
Lead Sponsor
Norwegian University of Science and Technology
Brief Summary

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

Detailed Description

Potential participants interested in the study will be screened for eligibility. Those who meet the eligibility criteria will be informed about the study, the expected investigations and its potential risks. All participants giving written informed consent will be enrolled into the study. Participants will be interviewed, given questionnaires, have blood and/or skin samples and clinical parameters taken. Cardiac function parameters will be measured using electrocardiography, echocardiography and magnetic resonance imaging.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
120
Inclusion Criteria
  • Patients with ICD-10 schizophrenia, schizotypal or delusional disorders (F20 to F29)
  • Both inpatient and outpatient
  • Capable of giving informed consent
Exclusion Criteria
  • Current or previous diagnosis of cancer
  • Current or previous treatment with chemotherapy
  • Current pregnancy
  • Mothers less than 6 months post-partum

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Diagnosed with SchizophreniaElectrocardiographyPatients 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.
No mental health diagnosisCardiac Magnetic Resonance ImagingParticipants 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.
No mental health diagnosisElectrocardiographyParticipants 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.
Diagnosed with SchizophreniaEchocardiographyPatients 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.
Diagnosed with SchizophreniaCardiac Magnetic Resonance ImagingPatients 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.
Diagnosed with SchizophreniaBlood samplingPatients 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.
No mental health diagnosisEchocardiographyParticipants 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.
No mental health diagnosisBlood samplingParticipants 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.
Primary Outcome Measures
NameTimeMethod
Left Ventricular Ejection Fraction (LVEF) measured by 2D EchocardiographyBaseline

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

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

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.

Fractional shortening measured by echocardiographyBaseline

Fractional shortening will be reported as a percentage (%)

Global longitudinal strain (GLS), echocardiographic parameterBaseline

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 (%)

Echocardiographic parameter TRpV, Tricuspid Regurgitation peak VelocityBaseline

TRpV is reported in m/s

Echocardiographic parameter, Indexed LV and RV stroke volumesBaseline

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)

Left Ventricular Ejection Fraction (LVEF) measured by 3D EchocardiographyBaseline

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

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

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

Echocardiography parameter of ratio of E/e'Baseline

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

Levels of NT-proBNPBaseline

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

DISC1 mRNA quantificationBaseline

Measured from blood samples and reported as fold change

Levels of high sensitive-CRPBaseline

Levels of HS-CRP mg/L

Levels of CK-MBBaseline

Levels of CK-MB is reported in µg/L

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

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.

TAPSE echocardiographic parameter of right ventricular longitudinal systolic functionbaseline

TAPSE will be reported in millimeters (mm)

Echocardiographic parameters septal e' and lateral e' velocitiesBaseline

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

Levels of Troponin IBaseline

Levels of Troponin I is reported in ng/L

Echocardiographic parameter MPI, Myocardial performance indexBaseline

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).

Echocardiographic parameter Mitral E/A ratioBaseline

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

Levels of IGF1Baseline

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

Levels of BDNF, brain derived neurotrophic factorBaseline

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

Levels of Transforming Growth Factor BetaBaseline

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

Interleukin levelsBaseline

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

Levels of Troponin TBaseline

Levels of Troponin T is reported in ng/L

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

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.

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

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.

Left ventricular mass measured by echocardiographyBaseline

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

Echocardiography parameter of peak E velocityBaseline

peak E velocity is reported in cm/s

Echocardiography parameter of E wave deceleration timeBaseline

E wave deceleration time is reported in milliseconds (ms)

Levels of Tumor Necrosis Factor alphaBaseline

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

Echocardiographic parameter LAVI, left atrial volume indexedBaseline

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

Echocardiographic parameter, S wave velocityBaseline

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

Levels of ANPBaseline

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

Levels of cardiac Myosin-Binding Protein CBaseline

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

Secondary Outcome Measures
NameTimeMethod
Number of participants with and abnormal ECGBaseline

Number of participants with an abnormal ECG will be reported in %

Incidence of cardiovascular disease or mortality as registered in a health registry on follow upWithin 15 years from start of study

Extraction of information from the cardiovascular disease registry and deaths registry between 10 - 15 years from the start of the study to determine incidence of cardiovascular disease outcomes for the study cohort

Systolic Blood PressureBaseline

Systolic Blood Pressure will be reported as mmHg

Potassium levelsBaseline

Potassium levels will be reported as mmol/L

Indexed LV mass, cardiac MRIBaseline

Indexed LV mass will be reported in g/m\^2 by indexing mass (g) to BSA (m\^2)

Number of participants with abnormal liver functionBaseline

Number of participants with abnormal liver function will be reported as %

Number of participants with abnormal kidney functionBaseline

Number of participants with abnormal kidney function will be reported as %

Number of participants with low Vitamin D levelsBaseline

Number of participants with low Vitamin D levels will be reported as %

native T1 time, cardiac MRIBaseline

native myocardial T1 relaxation time is reported in milliseconds (ms)

High-density lipoprotein, HDL-cholesterol levelsBaseline

HDL-cholesterol levels will be reported in mmol/L

Low-density lipoprotein, LDL-cholesterol levelsBaseline

LDL-cholesterol levels will be reported in mmol/L

Diastolic Blood PressureBaseline

Diastolic Blood Pressure will be reported as mmHg

Lipoprotein aBaseline

Lipoprotein a levels will be reported in mg/L

Magnesium levelsBaseline

Magnesium levels will be reported as mmol/L

Calcium levelsBaseline

Calcium levels will be reported as mmol/L

Sodium levelsBaseline

Sodium levels will be reported as mmol/L

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

Indexed LV and RV end-diastolic, end-systolic and stroke volumes will be reported in mL/m\^2, by indexing the volumes (mL) to BSA (m\^2)

LV Ejection Fraction, cardiac MRIBaseline

LVEF will be reported in percent (%)

ECG corrected QT intervalBaseline

corrected QT interval will be reported in milliseconds (ms)

Triglyceride levelsBaseline

Triglyceride will be reported in mmol/L

Heart rate measured on ECGBaseline

Heart rate measured on 12 lead ECG will be reported in beats per minute.

Number of participants with abnormal thyroid functionBaseline

Number of participants with abnormal thyroid function will be reported as %

Fasting glucose levelsBaseline

Fasting glucose levels will be reported in mmol/L

Glycated Hemoglobin (HbA1c) levelsBaseline

HbA1C will be reported in mmol/mol

Trial Locations

Locations (2)

Norwegian University of Science and Technology

🇳🇴

Trondheim, Norway

St Olavs Hospital, Trondheim University Hospital

🇳🇴

Trondheim, Norway

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