Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620001222932
Ethics application status
Approved
Date submitted
3/08/2020
Date registered
16/11/2020
Date last updated
7/07/2021
Date data sharing statement initially provided
16/11/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Developing a biomarker for anxiety disorders
Scientific title
Do hippocampus, insula and amygdala contribute to an anxiety syndrome biomarker in healthy participants and patients with anxiety disorder when given anxiolytic medications?
Secondary ID [1] 301934 0
'None'
Universal Trial Number (UTN)
U1111-1256-4071
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anxiety 318462 0
Panic 318463 0
Simple Phobia 318464 0
Generalized Anxiety 318465 0
Social Anxiety 318809 0
Psychological Distress 318810 0
Condition category
Condition code
Mental Health 316471 316471 0 0
Anxiety
Mental Health 316472 316472 0 0
Studies of normal psychology, cognitive function and behaviour
Mental Health 316822 316822 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Benzodiazepine (Triazolam):
-The administered doses (0.25 mg),
-once only,
-Oral tablet,

Buspirone:
-the administered doses (10 mg)
-once only
-Oral tablet

Pregabalin:
- the administered doses (75 mg)
- once only
- Oral tablet
Prozac/Fluoxetine:
- the administered doses (20 mg)
- once only
- Oral tablet

Each participant will receive one of these drug or placebo. We will obtain questionnaire measures of current mood and personality; Administer blinded study treatment; Wait 0.5 hour; Record fMRI in the SST or in the AACT; Repeat questionnaire measures of current mood (to assess mood changes); Ask participant to remain until it is safe to leave. Each cohort will complete their allocated task either SST or AACT.

We will recruit healthy volunteers (who have not received any medical or psychological treatment for anxiety, depression or emotional disorder within the last 12 months) and will follow the same procedure described in item 3 above. Patients with DSM-5 generalized anxiety (GAD); and social anxiety disorder (SAD) will be recruited and will follow the same procedure described above.
Intervention code [1] 318222 0
Diagnosis / Prognosis
Comparator / control treatment
Placebo (glucose oral capsule) in a tablet form.
Control group
Placebo

Outcomes
Primary outcome [1] 324623 0
Change in brain networks assessed using fMRI
Timepoint [1] 324623 0
30 minutes after intervention
Primary outcome [2] 325242 0
Compare the fMRI changes between healthy and diseased brains specially the task related changes in hippocampus and insula.
Timepoint [2] 325242 0
30 minutes
Primary outcome [3] 325651 0
Changes in HAM-A and STAI-T because of acute administration of anxiolytic drugs. (This is a composite outcome)
Timepoint [3] 325651 0
2 hour after dosing.
Secondary outcome [1] 385232 0
Use fMRI to investigate whether hippocampus is involved in anxiety processes,
Timepoint [1] 385232 0
2 hours after intervention
Secondary outcome [2] 387318 0
Use fMRI to investigate whether amygdala is involved in panic.
Timepoint [2] 387318 0
2 hours

Eligibility
Key inclusion criteria
We will recruit healthy participants.
Inclusion Criteria:
1. Capable of understanding and signing an informed consent
2. Aged 18-40 years on the day of consent.
3. Volunteers with no major illness in the previous 30 days
4. With no regular use of psychotropic medication in the last 12 months
5. No use of alcohol in the 24 hours before testing
For the clinical comparison, patients with DSM-5 generalized anxiety (GAD); and social anxiety disorder (SAD) will be recruited for our project
Inclusion Criteria:
1. 18-40 years old
2. suffering from ongoing symptoms of anxiety, fear, or panic and who are intending to seek treatment for this
3. otherwise be healthy (with no major illness in the previous 30 days)
4. with no regular use of psychotropic medication in the last 6 months and
5. no use of alcohol in the 24 hours before testing.
Minimum age
18 Years
Maximum age
40 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Healthy Volunteers:
Exclusion Criteria:
- Susceptibility to photosensitivity
- A history of seizure
- Any metal in your body, e.g., cardiac pacemaker, cochlea implant, intracranial vessel clips, artificial heart valve or vascular stent; a history of metal fragments in the eye; shrapnel within the body
- Are either pregnant or think you might be
- A history of claustrophobia
- Have received any medical or psychological treatment for anxiety, depression or emotional disorder within the last 12 months.
- Have a prior history of drug abuse
- Are suffering from acute or chronic physical disease such as heart and lung disease, influenza, diabetes, acute infections
- Are recovering from an accident, injury or operation.
Patient Volunteers (GAD and SAD)
Exclusion Criteria:
- Susceptibility to photosensitivity
- A history of seizure
- Any metal in your body, e.g., cardiac pacemaker, cochlea implant, intracranial vessel clips, artificial heart valve or vascular stent; a history of metal fragments in the eye; shrapnel within the body
- Are either pregnant or think you might be
- A history of claustrophobia
- Have a prior history of drug abuse
- Are suffering from acute or chronic physical disease such as heart and lung disease, influenza, diabetes, acute infections
- Are recovering from an accident, injury or operation.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
None
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
We will recruit 80 (20 in each intervention group) healthy volunteers for 4 different drugs. We will collect additional 160 healthy volunteers in fMRI to map the brain structures involved in anxiolytics and panicolytics response. We will recruit 60 patient volunteers to validate our findings. We will use ANOVA to investigate the differences in healthy and diseased brain and map the relevant brain areas responsible for anxiety and panic.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/12/2020
Actual
15/03/2021
Date of last participant enrolment
Anticipated
31/12/2023
Actual
Date of last data collection
Anticipated
31/12/2023
Actual
Sample size
Target
300
Accrual to date
55
Final
Recruitment outside Australia
Country [1] 22807 0
New Zealand
State/province [1] 22807 0
Otago

Funding & Sponsors
Funding source category [1] 306348 0
Government body
Name [1] 306348 0
Health Research Council of New Zealand
Country [1] 306348 0
New Zealand
Primary sponsor type
University
Name
University of Otago
Address
362 Leith Street
Dunedin 9016
New Zealand

PO Box 56
Dunedin 9054
New Zealand
Country
New Zealand
Secondary sponsor category [1] 307692 0
None
Name [1] 307692 0
Address [1] 307692 0
Country [1] 307692 0
Other collaborator category [1] 281545 0
University
Name [1] 281545 0
Professor Paul Glue
Address [1] 281545 0
Department of Psychological Medicine
Otago Medical School
PO Box 56
Dunedin 9054
University of Otago
Country [1] 281545 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306558 0
Northern B Health and Disability Ethics Committee
Ethics committee address [1] 306558 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
Ethics committee country [1] 306558 0
New Zealand
Date submitted for ethics approval [1] 306558 0
20/08/2020
Approval date [1] 306558 0
06/11/2020
Ethics approval number [1] 306558 0
20/NTB/196

Summary
Brief summary
Anxiety disorders” are the commonest mental disorders in New Zealand; but their diagnosis is still based on clinical symptom check lists not biological markers of specific causes. In our well-established neuropsychological theory, anxiety involves threat-approach controlled by specific brain structures in which hypersensitivity to input generates specific clinical syndromes. We have developed a specific non-invasive biomarker for threat-approach system activation in humans that shows hyperactivity in some clinical cases with source localisation to right inferior frontal regions. Our project will test this with fMRI and test for the involvement, predicted by our theory, of hippocampus, insula and amygdala. This should provide better understanding of the underlying causes of anxiety and ultimately provide targeted treatments; greatly improving treatment outcomes and cost-effectiveness.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 104282 0
Prof Neil McNaughton
Address 104282 0
Department of Psychology
University of Otago
PO Box 56
Dunedin 9054
New Zealand

Department of Psychology
University of Otago
William James Building
Level 1
275 Leith Walk
Dunedin 9016
Country 104282 0
New Zealand
Phone 104282 0
+64 34797634
Fax 104282 0
Email 104282 0
[email protected]
Contact person for public queries
Name 104283 0
Dr Shabah Shadli
Address 104283 0
Department of Psychology
University of Otago
William James Building
Level 1
275 Leith Walk
Dunedin 9016

Department of Psychology
University of Otago
PO Box 56
Dunedin 9054
New Zealand
Country 104283 0
New Zealand
Phone 104283 0
+64 34795835
Fax 104283 0
Email 104283 0
[email protected]
Contact person for scientific queries
Name 104284 0
Dr Shabah Shadli
Address 104284 0
Department of Psychology
University of Otago
William James Building
Level 1
275 Leith Walk
Dunedin 9016
Country 104284 0
New Zealand
Phone 104284 0
+64 34795835
Fax 104284 0
Email 104284 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All of the individual participant data collected during the trial, after de-identification will be shared.
When will data be available (start and end dates)?
31/12/2023 to 31/12/2025
Available to whom?
Only researchers who provide a methodologically sound proposal, case-by-case basis at the discretion of Primary Sponsor.
Available for what types of analyses?
To achieve the aims in the approved proposal, or for IPD meta-analyses.
How or where can data be obtained?
access subject to approvals by Principal Investigator (please contact Dr Shabah Shadli ([email protected]) or Professor Neil McNaughton ([email protected])


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.