ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12607000141448

Ethics application status

Approved

Date submitted

20/02/2007

Date registered

23/02/2007

Date last updated

26/08/2014

Type of registration

Prospectively registered

Titles & IDs

Public title

Effects of Oxytocin on Amygdala Response to Threat in Generalised Social Anxiety Disorder: A Functional Magnetic Resonance Imaging (fMRI) Study

Scientific title

A placebo-controlled, randomised phase III trial investigating the effects of oxytocin, a neuropeptide, on the neural circuit (i.e. amgydala) involved in threat processing in Generalised Social Anxiety Disorder using functional magnetic resonance imaging (fMRI).

Secondary ID [1]

Nil know

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

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

Generalised Social Anxiety Disorder

Condition category

Condition code

Mental Health

Anxiety

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Two intranasal treatment conditions: (1) Oxytocin Nasal Spray (24IU or 40.3mg) and (2) Placebo. Administration at 50 mins prior to fMRI scanning procedure. There is a minimum washout period of 1 week in between 2 fMRI sessions. The two groups, involving patients with Generalised Social Anxiety Disorder (GSAD) and healthy controls, will both receive the same interventions (placebo and oxytocin) during the time span of the study, but in different sequences during the study. All participants act as their own control due to placebo condition. However it is also of interest to compare the group of Generalised Social Anxiety Disorder patient with a control/comparison group of healthy controls. The allocation of the conditions is blinded and randomised.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Placebo

Control group

Placebo

Outcomes

Primary outcome [1]

fMRI data will be collected to investigate whether oxytocin affects the amygdala response to threatening (vs. non-threatening) facial expression processing in patients with Generalised Social Anxiety Disorder (GSAD) relative to healthy controls.

Timepoint [1]

50 minutes post drug administration

Secondary outcome [1]

The fMRI data collected 50 minutes post drug adminstration will also be used to investigate the effects of oxytocin (vs. placebo) on functional connectivity (ie. Amygdala-Brainstem, Amygdala-Insula) in patients with Generalised Anxiety Disorder (GSAD) compared to healthy controls.

Timepoint [1]

Functional connectivity will be investigated during the analysis using correlation analysis, which is done post data collection during data analysis. This data used is collected at 50 minutes post drug administration.

Eligibility

Key inclusion criteria

Right-handed, non-smokers, psychotropic medication free for a minimum of 2 weeks (8 weeks for fluoxetine, 4 weeks for monoamine oxidase inhibitors), not taking hormonal contraceptives, and do not have comorbid alcohol or substance abuse or dependence. Additional inclusion for GSAD participants - Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) GSAD as primary diagnosis.

Minimum age

18 Years

Maximum age

55 Years

Sex

Both males and females

Can healthy volunteers participate?

Yes

Key exclusion criteria

Clinically significant medical or neurologic condition (not applicable to GSAD patients, see inclusion criteria), current/recent depressive episode, life history of bipolar, schizophrenia, obsessive compulsive disorder, post-traumatic stress disorder or presence of organic mental syndrome, mental retardation, or pervasive developmental disorder, pregnancy or lactation, presence of ferrous-containing metals within the body, inability to tolerate small, enclosed spaces without anxiety.

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Allocation concealment will be conducted by labeling the spray bottles with numbers

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Computerised randomisation procedure

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

Intervention assignment

Crossover

Other design features

This is a double-blind design study where both the assessor and the participant will be blind to which drug condition is applied at the time of testing.

Phase

Phase 3

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

25/04/2007

Actual

12/03/2008

Date of last participant enrolment

Anticipated

Actual

17/11/2009

Date of last data collection

Anticipated

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Funding & Sponsors

Funding source category [1]

University

Name [1]

School of Psychology, Psychiatry and Psychological Medicine, Monash University

Address [1]

School of Psychology, Psychiatry and Psychological Medicine, Monash University, Clayton, 3800

Country [1]

Australia

Primary sponsor type

University

Name

School of Psychology, Psychiatry and Psychological Medicine, Monash University

Address

School of Psychology, Psychiatry and Psychological Medicine, Monash University, Clayton, 3800

Country

Australia

Secondary sponsor category [1]

None

Name [1]

None

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Monash Medical Centre-Southern Health Human Research Ethics Committee

Ethics committee address [1]

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

19/03/2007

Approval date [1]

21/05/2007

Ethics approval number [1]

Ethics committee name [2]

Monash University-Standing Committee on Ethics in Research involving Humans

Ethics committee address [2]

Ethics committee country [2]

Australia

Date submitted for ethics approval [2]

Approval date [2]

31/05/2007

Ethics approval number [2]

Summary

Brief summary

The proposed study will examine if intranasal oxytocin can modulate the neural circuitry (especially the amygdala) response to threat in patients with Generalised Social Anxiety Disorder (GSAD).  Two treatment conditions are involved: Oxytocin vs. Placebo.  Participants (20 GSAD, 20 healthy controls) are required to undergo two functional magnetic resonsonance imaging (fMRI) sessions during which they will be asked to complete two emotional facial expression tasks.  It is hypothesised that under placebo, patients with GSAD will show exaggerated amygdala activity as well as functional connectivity to threatening (i.e. angry and fearful) facial stimuli compared to healthy controls.  Under oxytocin, such effects will be absent and amgydala activation and functional connectivity during threat processing will be reduced.

Trial website

Trial related presentations / publications

Publications:
1. Gorka SM, Fitzgerald DA, Labuschagne I, Hosanagar A, Nathan PJ, Phan KL. Oxytocin Modulates Amygdala Functional Connectivity during Social Threat in Generalized Social Anxiety Disorder. Neuropsychopharmacology. Accepted July 2014.
2. Dodhia S, Hosanagar A, Fitzgerald DA, Labuschagne I, Wood A, Nathan PJ, Phan KL. Modulation of Resting-State Amygdala-Frontal Functional Connectivity by Oxytocin in Generalized Social Anxiety Disorder. Neuropsychopharmacology, 39, 2061-2069. 
3. Sripada CS, Phan KL, Labuschagne I, Welsh R, Nathan PJ, Wood AG. (2013). Oxytocin enhances resting state connectivity between amygdala and medial frontal cortex. International Journal of Neuropsychopharmacology, 16(2), 255-260. 
4. Labuschagne I, Phan KL, Wood A, Angstadt M, Chua P, Heinrichs M, Stout J, Nathan PJ.  (2012). Medial frontal hyperactivity to sad faces in generalized social anxiety disorder and modulation by oxytocin. International Journal of Neuropsychopharmacology, 15(7), 883-896. 
5. Labuschagne I, Phan KL, Wood A, Angstadt M, Chua P, Heinrichs M, Stout J, Nathan PJ. (2010). Oxytocin attenuates amygdala reactivity to fear in generalised social anxiety disorder.  Neuropsychopharmacology, 35, 2403-2413.  

Published Abstracts:
1. Hosanagar A, Sripada C, Angstadt M, Labuschagne I, Welsh R, Wood A, Nathan PJ, Phan, K. L. (2012). Disrupted default mode network connectivity in generalised social anxiety disorder at rest: an oxytocin-placebo pharmaco-fMRI study. Biological Psychiatry, 71, 176S-176S. April 15.
2. Nathan PJ, Labuschagne I, Wood A, et al. (2010). Oxytocin attenuates amygdala response to fear in social anxiety disorder. Journal of Psychopharmacology, 24, A75-A75, Aug 2010.
3. Labuschagne I, Phan KL, Wood A, et al. (2010). Oxytocin attenuates amygdala response to fear in social anxiety disorder. Biological Psychiatry, 67 (9), 203S-203S, May 1.

Public notes

Contacts

Principal investigator

Name

Prof Pradeep Nathan

Address

Department of Psychiatry
Cambridge University
Forvie Site, Robinson Way
Cambridge CB2 0SZ, UK

Country

United Kingdom

Phone

+44 1223296081

Fax

pn254@cam.ac.uk

Contact person for public queries

Name

Izelle Labuschagne

Address

Behavioural Neuroscience Laboratory
School of Psychology
Psychiatry and Psychological Medicine
Monash University
Clayton VIC 3800

Country

Australia

Phone

+61 3 9594 5543

Fax

Izelle.Labuschagne@med.monash.edu.au

Contact person for scientific queries

Name

Pradeep J. Nathan

Address

Department of Psychiatry
Cambridge University
Forvie Site, Robinson Way
Cambridge CB2 0SZ, UK

Country

Australia

Phone

+61 3 99054319

Fax

pn254@cam.ac.uk

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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