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

The Protein Disrupted in Schizophrenia 1 (DISC1) as a Novel Biomarker for Cardiac Disease - The Link Between DISC1 and Cardiac Function in Patients With Schizophrenia

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

Study Overview

• Status: Recruiting
• Conditions: Heart Diseases; Schizophrenia; Heart; Functional Disturbance
• Intervention / Treatment: Diagnostic test: Echocardiography; Diagnostic test: Cardiac Magnetic Resonance Imaging; Diagnostic test: Electrocardiography; Other: Blood sampling

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.

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

• Study Contact: Name: Morten A Høydal, PhD; Phone Number: +47 48134843; Email: morten.hoydal@ntnu.no
• Study Contact Backup: Name: Rita Brekke, MD,MSc; Phone Number: +47 45111574; Email: rita.brekke@ntnu.no

Study Locations

• Norway
  • Trondheim, Norway
    • Recruiting
    • St Olavs Hospital, Trondheim University Hospital
    • Contact: Mette E Tunset, MD; Email: mette.elise.tunset@stolav.no
    • Contact: Morten B Schou, PhD; Email: morten.brix.schou@stolav.no
  • Trondheim, Norway
    • Recruiting
    • Norwegian University of Science and Technology
    • Contact: Morten A Høydal, PhD; Phone Number: +47 48134843; Email: morten.hoydal@ntnu.no
    • Contact: Rita Brekke, MD, MSc; Phone Number: +47 45111574; Email: rita.brekke@ntnu.no

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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; ultrasound assessment of heart structure, volume and function; Other Names: Echo; Diagnostic test: Cardiac Magnetic Resonance Imaging; MRI assessment of heart structure, volume, function and tissue characteristics; Other Names: Cardiac MRI; CMRI; Diagnostic test: Electrocardiography; Assessment of cardiac rhythm and electrical activity; Other Names: ECG; Holter; Other: Blood sampling; To measure DISC1 mRNA expression and other potential biomarkers
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; ultrasound assessment of heart structure, volume and function; Other Names: Echo; Diagnostic test: Cardiac Magnetic Resonance Imaging; MRI assessment of heart structure, volume, function and tissue characteristics; Other Names: Cardiac MRI; CMRI; Diagnostic test: Electrocardiography; Assessment of cardiac rhythm and electrical activity; Other Names: ECG; Holter; Other: Blood sampling; To measure DISC1 mRNA expression and other potential biomarkers

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
native T1 time, cardiac MRI	native myocardial T1 relaxation time is reported in milliseconds (ms)	Baseline
Indexed LV and RV end-diastolic, end-systolic and stroke volumes, cardiac MRI	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)	Baseline
Indexed LV mass, cardiac MRI	Indexed LV mass will be reported in g/m^2 by indexing mass (g) to BSA (m^2)	Baseline
LV Ejection Fraction, cardiac MRI	LVEF will be reported in percent (%)	Baseline
ECG corrected QT interval	corrected QT interval will be reported in milliseconds (ms)	Baseline
Number of participants with and abnormal ECG	Number of participants with an abnormal ECG will be reported in %	Baseline
Number of participants with abnormal liver function	Number of participants with abnormal liver function will be reported as %	Baseline
Number of participants with abnormal kidney function	Number of participants with abnormal kidney function will be reported as %	Baseline
Number of participants with abnormal thyroid function	Number of participants with abnormal thyroid function will be reported as %	Baseline
Number of participants with low Vitamin D levels	Number of participants with low Vitamin D levels will be reported as %	Baseline
Incidence of cardiovascular disease or mortality as registered in a health registry on follow up	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	Within 15 years from start of study
Triglyceride levels	Triglyceride will be reported in mmol/L	Baseline
High-density lipoprotein, HDL-cholesterol levels	HDL-cholesterol levels will be reported in mmol/L	Baseline
Low-density lipoprotein, LDL-cholesterol levels	LDL-cholesterol levels will be reported in mmol/L	Baseline
Fasting glucose levels	Fasting glucose levels will be reported in mmol/L	Baseline
Glycated Hemoglobin (HbA1c) levels	HbA1C will be reported in mmol/mol	Baseline
Heart rate measured on ECG	Heart rate measured on 12 lead ECG will be reported in beats per minute.	Baseline
Systolic Blood Pressure	Systolic Blood Pressure will be reported as mmHg	Baseline
Diastolic Blood Pressure	Diastolic Blood Pressure will be reported as mmHg	Baseline
Lipoprotein a	Lipoprotein a levels will be reported in mg/L	Baseline
Magnesium levels	Magnesium levels will be reported as mmol/L	Baseline
Calcium levels	Calcium levels will be reported as mmol/L	Baseline
Sodium levels	Sodium levels will be reported as mmol/L	Baseline
Potassium levels	Potassium levels will be reported as mmol/L	Baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alcohol intake at baseline using The Alcohol Use Disorders Identification Test Consumption (AUDIT-C) questionnaire	The AUDIT-C is a validated 3-item questionnaire for identification of alcohol misuse. Each item has 5 possible responses, each scored from 0 to 4 points. Possible scores range from 0 to 12. The score cut-off for alcohol misuse is 4 points in men and 3 points in women	Baseline
Average length of inpatient stay for schizophrenia related admissions	The average length of inpatient stays will be reported as number of days and derived from the total number of days spent admitted over the total number of admissions.	Baseline
Need of Care based on number of total hospital admission for schizophrenia	Number of hospital admissions	Baseline
Severity scoring of psychiatric symptoms using Clinical Global Impressions (CGI) Scale - Severity	CGI for severity is a validated scale used to assess psychiatric illness severity by a clinician. Possible scores range from 1 (Normal, not at all ill) to 7 (Among the most extremely ill patients)	Baseline
Schizophrenia symptom severity as scored on the Positive and Negative Syndrome Scale (PANSS)	PANSS/SCI-PANSS are validated clinician administered scale used to measure symptom severity in schizophrenia and consists of 30 items divided into 3 subscales: Positive Scale, Negative Scale and the General Pathology Scale. Each subscale can be scored from 1 (absent) to 7 (extreme). Possible scores for the Positive and Negative scales range from 7 - 49, and for the General Psychopathology Scale range from 16 - 112. The further developed SCI-PANSS (structured clinical interview - for the Positive and Negative Syndrome Scale).	Baseline
Duration of schizophrenia	Duration of schizophrenia as determined from self reported year of first episode of diagnosis/ or from date of diagnosis	Baseline
Length of treatment with an antipsychotic medication	The length of treatment with an antipsychotic medication will be reported in years	Baseline
Antipsychotic dosage in daily equivalent dosage of chlorpromazine	Antipsychotic dosages will also be converted to daily equivalent dosage of chlorpromazine for comparison across different medication will be reported in mg/day	Baseline
Smoking status	Number of participants who smoke will be reported in percent (%)	Baseline
Waist Hip Ratio	Waist Hip measurements will be reported as a ratio	Baseline
Body Mass Index	Body Mass Index, BMI will be derived from participants weight and height and reported as kg/m^2	Baseline
Body fat percent	Body fat percent from body composition analysis will be reported in %	Baseline
Physical Activity	Baseline physical activity measured using the International Physical Activity Questionnaire (IPAQ) The IPAQ is validated in schizophrenia populations and the IPAQ has been validated in Norwegian populations. It is a self reported scoring system assessing physical activity over the last seven days. Physical activity can be then represented in minutes/week or MET-minutes/week.	Baseline
Body muscle composition	Body muscle mass will be reported in kg	Baseline
Smoking history	Smoking will be quantified and reported as pack/years	Baseline
Age of participant	Age of participant will be reported in years	Baseline
Gender of participant	Gender of participant will be reported as male or female	Baseline

Collaborators and Investigators

• Sponsor: Norwegian University of Science and Technology
• Collaborators: St. Olavs Hospital
• Investigators: Study Director: Morten A Høydal, PhD, Norwegian University of Science and Technology

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2023
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): June 1, 2038

Study Registration Dates

• First Submitted: December 11, 2023
• First Submitted That Met QC Criteria: March 4, 2024
• First Posted (Actual): March 12, 2024

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: DISC1; Disrupted in Schizophrenia 1; Cardiac Biomarker
• Additional Relevant MeSH Terms: Mental Disorders; Cardiovascular Diseases; Schizophrenia Spectrum and Other Psychotic Disorders; Heart Diseases; Schizophrenia
• Other Study ID Numbers: 606103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All of the individual participant data collected during the study, after deidentification can be shared.
• IPD Sharing Time Frame: During the whole project period up to 15 years.
• IPD Sharing Access Criteria: For cooperative research and publication within Norway, the EU and the US, for purposes inline with those in the Study protocol.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No