ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12617000086369

Ethics application status

Approved

Date submitted

10/01/2017

Date registered

16/01/2017

Date last updated

16/01/2017

Type of registration

Retrospectively registered

Titles & IDs

Public title

A combined PET-fMRI study of frontostriatal dysfunction in first episode psychosis

Scientific title

A combined PET-fMRI study of frontostriatal dysfunction in first episode psychosis

Secondary ID [1]

nil

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Psychosis

Condition category

Condition code

Mental Health

Psychosis and personality disorders

Neurological

Other neurological disorders

Intervention/exposure

Study type

Observational

Patient registry

False

Target follow-up duration

Target follow-up type

Description of intervention(s) / exposure

1. Baseline
All participants will complete a baseline assessment

a. Patients will complete the following over 2 visits ideally within one week:
i. Clinical assessment (3 hours)
ii. PET-MRI imaging (3 hours)

The same protocol will be used for healthy controls, though the clinical assessment will be briefer, involving some questionnaires and a structured diagnostic interview

a. Healthy control participants will complete the following over 2 visits ideally within one week:
i. Clinical assessment (3 hours)
ii. PET-MRI imaging (3 hours)

2. 12-month follow-up
Patients only will complete a 12-month follow-up assessment, involving:
a. Detailed clinical assessment (3 hours)
No brain imaging is required at 12-month follow-up

Intervention code [1]

Diagnosis / Prognosis

Comparator / control treatment

Healthy controls with no personal/family history of neurological/psychiatric illness will be age and gender matched to the patient group.

Control group

Active

Outcomes

Primary outcome [1]

Identify specific, neural-circuit-level drivers of variations in striatal FDOPA levels by identifying which specific measure of fMRI functional connectivity makes the strongest unique contribute to the striatal FDOPA signal.

Instrument: PET-MRI scan

Timepoint [1]

Baseline

Secondary outcome [1]

Compare striatal FDOPA levels between patients and controls.

Instrument: PET-MRI scan

Timepoint [1]

Baseline

Secondary outcome [2]

Identify which specific circuit-level driver of striatal FDOPA variations different between people with psychosis and healthy controls.

Instrument: PET-MRI scan, clinical assessment

Timepoint [2]

Baseline, 12 month follow-up

Eligibility

Key inclusion criteria

Patient Inclusion criteria:

*Experiencing a first episode of psychosis (one or more psychotic symptoms on a daily basis for at least one week) and meeting diagnostic criteria for one of the following DSM-IV disorders: schizophreniform psychosis, schizophrenia, schizoaffective disorder, delusional disorder, brief psychosis, major depressive disorder or bipolar disorder with psychotic features, or psychosis NOS.
*Age range 18-25 years
*Within 3 months of commencing regular antipsychotic treatment; or lifetime cumulative exposure of < 3 months; or no antipsychotic treatment for at least one year
*Ability to provide informed consent as determined either via the clinical opinion of the treating medical physician, or the administration, by one of the research team, of the MacArthur Competence Assessment Tool for Clinical Research.

Healthy Control Participant Inclusion criteria:
* Psychiatrically healthy individual aged 18-25 years

Minimum age

18 Years

Maximum age

25 Years

Sex

Both males and females

Can healthy volunteers participate?

Yes

Key exclusion criteria

Patient Exclusion criteria:
* Primary diagnosis of Borderline Personality Disorder or Post-Traumatic Stress Disorder
* Intellectual disability
* Colour blindedness
* Diagnosis of substance dependence
* History of neurological disorder, brain injury, or significant loss of consciousness
* MRI/PET contraindications (pregnancy, breastfeeding, metal implants)
* Contraindications for Carbidopa and Entacapone (treatment with MAO inhibitors, blood/needle phobia, glaucoma, malignant melanoma, phaechromocytoma, rhabdomylosis, history of major medical condition such as diabetes, cardiovascular disease, hepatic/renal failure, etc).

Healthy Control Participant Exclusion criteria:
*Personal history of psychiatric or neurologic illness
*First-degree relatives with psychotic illness
*Intellectual disability
*History of neurological disorder, brain injury, or significant loss of consciousness
* MRI/PET contraindications (pregnancy, breastfeeding, metal implants)
* Contraindications for Carbidopa and Entacapone (treatment with MAO inhibitors, blood/needle phobia, glaucoma, malignant melanoma, phaechromocytoma, rhabdomylosis, history of major medical condition such as diabetes, cardiovascular disease, hepatic/renal failure, etc).

Study design

Purpose

Natural history

Duration

Longitudinal

Selection

Case control

Timing

Prospective

Statistical methods / analysis

Patlak graphical analysis will be used to compute 18F-DOPA influx rate constants (Ki values)
fMRI data will be processed and analysed. Specifically, six spherical seed regions will be placed in the dorsal and ventral striatum to extract representing time courses of activity fluctuations in each sub-region. These time courses will be entered as covariates along with other signals modeling various noise sources in the data into a general linear model. This model will be fitted to each individual’s functional data on a voxel-wise basis to identify regions showing significant functional connectivity with each striatal area. Group differences in striatal functional connectivity will be compared using two-sample t-tests. Effective connectivity within these networks will be modeled using dynamic causal modeling (DCM) an established fMRI procedure for inferring causal influences between neural systems.

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

Actual

17/12/2015

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

100

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

NHMRC

Address [1]

Level 1
16 Marcus Clarke Street
Canberra ACT 2601

Country [1]

Australia

Primary sponsor type

University

Name

Monash University

Address

Wellington Rd, Clayton VIC 3168

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Melbourne Health HREC

Ethics committee address [1]

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

15/08/2014

Ethics approval number [1]

2014.047

Summary

Brief summary

Psychosis is a debilitating neuropsychiatric syndrome characterized by delusions, hallucinations, disorganized thinking and cognitive and emotional disturbances. It is a defining characteristic of schizophrenia, and occurs frequently in other major mental illnesses such as depression and bipolar disorder. All current treatments for psychosis modulate levels of the neurotransmitter dopamine (DA), and it is thought that DA  dysregulation within circuits linking frontal brain regions with a set of subcortical nuclei called the striatum (the so called frontostriatal circuits) is a final common pathway for the emergence of psychotic symptoms. Precisely how this dysregulation arises however, remains a mystery.
This study will be the first to combine Positron Emission Technology (PET) measures of striatal DA function with functional Magnetic Resonance Imaging (fMRI) measures of frontostriatal connectivity to investigate the way in which altered subcortical dopamine may give rise to, or arise from, aberrant frontostriatal connectivity.
The project has three specific aims:
1. characterise the direct relationship between PET markers of striatal DA function and fMRI measures of frontostriatal functional dysconnectivity;
2. determine whether striatal DA abnormalities are a cause or consequence of frontostriatal dysconnectivity; and
3. investigate the potential of these two phenotypes as clinical biomarkers by determining whether they can predict patients’ 12month clinical outcome.
We will recruit 50 First Episode Psychosis (FEP) patients and 50 healthy controls to take part in the study. All participants will complete a clinical and brain imaging assessment at baseline. The brain imaging assessment will involve MRI and PET.
FEP patients will additionally complete a clinical assessment after a 12 month
followup period. No brain imaging will be conducted at this time. No followup of controls will be performed.
During the followup period, the research staff will maintain regular contact with the patients' clinical team. Information on treatments will be acquired, enabling us to account for variations in treatment protocols in our analyses.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

A/Prof Alex Fornito

Address

Monash Biomedical Imaging
770 Blackburn Rd, Clayton VIC 3168

Country

Australia

Phone

+61 3 99029796

Fax

alex.fornito@monash.edu

Contact person for public queries

Name

Amy Finlay

Address

Monash Biomedical Imaging
770 Blackburn Rd, Clayton VIC 3168

Country

Australia

Phone

+61 3 9902 9803

Fax

med-mcin-fdopa@monash.edu

Contact person for scientific queries

Name

Alex Fornito

Address

Monash Biomedical Imaging
770 Blackburn Rd, Clayton VIC 3168

Country

Australia

Phone

+61 3 99029796

Fax

alex.fornito@monash.edu

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

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Documents added automatically

No additional documents have been identified.

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