The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12612000190808
Ethics application status
Approved
Date submitted
27/01/2012
Date registered
14/02/2012
Date last updated
21/11/2013
Type of registration
Retrospectively registered

Titles & IDs
Public title
The Impact of Social Cognition Training and Oxytocin on Social Functioning in Early Psychosis.
Scientific title
A Randomised Controlled Clinical Trial Investigating the Impact of Social Cognition Training and Oxytocin on Social Functioning in Early Psychosis.
Secondary ID [1] 279804 0
Nil
Universal Trial Number (UTN)
U1111-1127-4918
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Early Psychosis 285627 0
Condition category
Condition code
Mental Health 285819 285819 0 0
Psychosis and personality disorders
Mental Health 285820 285820 0 0
Schizophrenia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Social Cognition Training (SCT):
SCT is an evidence based psychosocial intervention administered by Clinical Psychologists with expertise in social information processing deficits. Targeted treatment addresses four key areas of social cognitive impairement; emotion recognition, theory of mind, social knowledge and attribution bias. Intervention is comprised of various online training programs and group based activities. The 6 week treatment program is delivered weekly (2 x 1 hour sessions) in a small group format of 6-8 participants for a total of 12 sessions. Participants will also undergo treatment as usual (TAU), that is, continuing their standard routine clinical care (e.g., psychiatrist appointment).

Oxytocin (OT) Nasal Spray:
Research focused on the neurobiology of social cognition and behaviour highlights the central role of Oxytocin (OT). This neuropeptide is implicated in modulating peer recognition and social approach/avoidance in mammals. It also plays a critical role in the development of partner preference and social bonds.

Approved by the Therapeutic Goods Administration (TGA), OT is supplied by a registered compounding chemist and is matched with an identical placebo containing all ingredients except the active OT. Participants are assigned one pre-packed treatment containing identical active OT or placebo nasal spray according to the randomisation schedule developed by the chemist. OT or placebo is administered twice daily for the 6 weeks of social cognition training. We use a standard adult dose of OT that has been used in previous human studies, 24 International Units (IU; 1 puff per nostril with each puff containing 12 IU) twice daily. Moreover, participants undergoing SCT will be asked to administer an additional 24 IU dose of OT (or placebo) 10 minutes prior to the commencement of group.
Intervention code [1] 284080 0
Behaviour
Intervention code [2] 284081 0
Treatment: Drugs
Intervention code [3] 284085 0
Prevention
Comparator / control treatment
SCT + Placebo Nasal Spray (saline solution)
Control group
Placebo

Outcomes
Primary outcome [1] 286335 0
Change in Social Cognition
1. The Reading the Mind in the Eyes Test (RMET; Baron-Cohen et al. 2001)

The RMET consists of 36 images displaying the eye-region of human faces and depict various emotional expressions. RMET tests the inference of the internal state from subtle affective facial expression. The participant is asked to pick which of the four words best describes what the person in the photo is thinking or feeling. RMET yields a total score of correct answers. The RMET has been used widely in the research literature to demonstrate social cognitive deficits in patients with schizophrenia.
Timepoint [1] 286335 0
Conducted at three assessment time points; pre assessment (following referral and diagnostic interview), post assessment (within two weeks following completion of group) and 3-month follow up.
Primary outcome [2] 286369 0
Change in Social Function
1. The Social Functioning Scale (SFS; Birchwood et al. 1990)

The Social Functioning Scale (SFS) assesses the most relevant areas of social functioning for the support of patients with schizophrenia within the community. The purpose of the scale is to provide a detailed evaluation of both the strengths and weaknesses of each patient?s social functioning and to identify specific objectives of intervention. The SFS covers seven areas of social functioning: (1) Withdrawal; (2) Interpersonal behavior; (3) Prosocial activities; (4) Recreation; (5) Independence-Performance; (6) Independence-Competence; and (7) Employment/Occupation.
Timepoint [2] 286369 0
Conducted at three assessment time points; pre assessment (following referral and diagnostic interview), post assessment (within two weeks following completion of group) and 3-month follow up.
Primary outcome [3] 286370 0
Change in Positive and Negative Symptom Severity
1. The Scale for the Assessment of Positive Symptoms (SAPS; Andreasen, 1984a)

The SAPS and SANS are hallmark assessment measures of positive and negative symptoms that characterize Schizophrenia. The SAPS is a 34-item scale used to rate the severity of four positive symptoms of schizophrenia: Hallucinations, Delusions, Bizarre Behavior, and Formal Thought Disorder. Each symptom cluster is evaluated on the basis of a global rating. Symptoms are rated on a 6-point scale ranging from zero, for "none," to 5 for "severe." The SANS includes items reflecting the severity of 19 specific negative symptoms regrouped into five symptom subscales: Affective Flattening, Alogia, Avolition-Apathy, Anhedonia-Asociality, and Attention deficit. Each subscale includes a global rating resulting in a total of 24 items.
Timepoint [3] 286370 0
Conducted at three assessment time points; pre assessment (following referral and diagnostic interview), post assessment (within two weeks following completion of group) and 3-month follow up.
Secondary outcome [1] 295696 0
Change in Emotion Recognition Ability
1. The Facial Expressions of Emotions: Stimuli and Tests (FEEST; Young et al. 2002)
Timepoint [1] 295696 0
Conducted at three assessment time points; pre assessment (following referral and diagnostic interview), post assessment (within two weeks following completion of group) and 3-month follow up.
Secondary outcome [2] 295697 0
Change in Theory of Mind Ability
1. The Faux Pas Recognition Test (Stone et al. 1998)
2. False Belief Picture Sequencing Task (FBPST; Langdon et al. 2007)
3. The Movie Stills Task (Adolphs & Tranel, 2003)
4. The Cambridge Empathy Quotient (EQ; Lawrence et al. 2004)
Timepoint [2] 295697 0
Conducted at three assessment time points; pre assessment (following referral and diagnostic interview), post assessment (within two weeks following completion of group) and 3-month follow up.
Secondary outcome [3] 295698 0
Change in Attribution Style
1. The Ambiguous Intentions Hostility Questionnaire-Ambiguous items (AIHQ; Combs et al. 2007)
Timepoint [3] 295698 0
Conducted at three assessment time points; pre assessment (following referral and diagnostic interview), post assessment (within two weeks following completion of group) and 3-month follow up.
Secondary outcome [4] 295699 0
Change in Social Interaction Ability
1. The Interpersonal Competence Questionnaire (ICQ; Buhrmester et al. 1988)
2. The Social Skills Performance Assessment Task (SSPA; Patterson et al. 2001)
3. Sheehan Disability Scale (SDS; Sheehan, 1983)
Timepoint [4] 295699 0
Conducted at three assessment time points; pre assessment (following referral and diagnostic interview), post assessment (within two weeks following completion of group) and 3-month follow up.
Secondary outcome [5] 295700 0
Change in Social-Cognitive Mechanisms
1. The Eye-Gaze Task (see Guastella et al. 2008)
Timepoint [5] 295700 0
Conducted at three assessment time points; pre assessment (following referral and diagnostic interview), post assessment (within two weeks following completion of group) and 3-month follow up.
Secondary outcome [6] 295701 0
Change in Biological Measures
1. Peripheral measures of blood to assess OT plasma levels and /or OT to AVP (vasopressin) ratio
2. Heart Rate Variability measured by non-invasive recording discs placed on the wrist and neck.
Timepoint [6] 295701 0
Conducted at three assessment time points; pre assessment (following referral and diagnostic interview), post assessment (within two weeks following completion of group) and 3-month follow up.
Secondary outcome [7] 295702 0
Change in Symptom Severity
1. Kessler Psychological Distress Scale (K-10; Kessler et al. 2010)
2. Depression, Anxiety and Stress Scales (DASS 21; Lovibond & Lovibond, 1995)
3. Social Interaction Anxiety Scale (SIAS; Mattick & Clarke, 1989)
4. Clinical Global Impression (CGI; Roberts et al. 2009)
Timepoint [7] 295702 0
Conducted at three assessment time points; pre assessment (following referral and diagnostic interview), post assessment (within two weeks following completion of group) and 3-month follow up.

Eligibility
Key inclusion criteria
- Meets DSM-IV-TR criteria for current or past diagnosis of Schizophrenia Spectrum Psychosis based on the SCID. (Schizophrenia, Schizophreniform Disorder, or Schizoaffective Disorder)
- Within the first three years of treatment for psychosis
- Stabilised on psychotropic medication for atleast 6 weeks prior to participation.
- Intelligence quotient of 70 or above
Minimum age
16 Years
Maximum age
30 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Florid psychotic sympotms and/or mania likely to require acute clinical intervention
- Current substance dependence

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)
This study employs a randomised controlled between-subject, double blind design. According to the randomisation schedule developed by the compounding chemist, participants are assigned to one of two treatment conditions (a) SCT combined with adjunctive OT and TAU or, (b) SCT combined with an adjunctive placebo and TAU. Drug will be stratified by gender, years of education, duration of illness, and concurrent medication type.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 4884 0
2050
Recruitment postcode(s) [2] 4885 0
2046
Recruitment postcode(s) [3] 4886 0
2131
Recruitment postcode(s) [4] 4887 0
2041
Recruitment postcode(s) [5] 4888 0
2137
Recruitment postcode(s) [6] 4889 0
2132
Recruitment postcode(s) [7] 4890 0
2042
Recruitment postcode(s) [8] 4891 0
2040
Recruitment postcode(s) [9] 4892 0
2045
Recruitment postcode(s) [10] 4893 0
2204
Recruitment postcode(s) [11] 4894 0
2130
Recruitment postcode(s) [12] 4895 0
2007
Recruitment postcode(s) [13] 4896 0
2560

Funding & Sponsors
Funding source category [1] 284549 0
Government body
Name [1] 284549 0
ARC Linkage Grant
Address [1] 284549 0
Level 2, 11 Lancaster Place
Majura Park ACT 2609
AUSTRALIA
Country [1] 284549 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
College St University of Sydney NSW 2006
Country
Australia
Secondary sponsor category [1] 283499 0
None
Name [1] 283499 0
Address [1] 283499 0
Country [1] 283499 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 286533 0
Human Research Ethics Committee (HREC) - The University of Sydney
Ethics committee address [1] 286533 0
Level 6
Jane Foss Russell Building G02
University of Sydney NSW 2006
Ethics committee country [1] 286533 0
Australia
Date submitted for ethics approval [1] 286533 0
06/09/2010
Approval date [1] 286533 0
17/12/2010
Ethics approval number [1] 286533 0
13166

Summary
Brief summary
Evidence demonstrates that social cognition training improves social cognition and social functioning in individuals with a psychotic disorder. The aim of this study is to determine the critical cognitive and biological markers underlying the effects of social cognition training and the degree to which they predict changes in social functioning for young people with a psychotic illness.
As suggested in the literature, face perception, emotion recognition, theory of mind and attribution bias are key cognitive markers of social functioning in humans. We speculate that OT may further underlie these cognitive changes via feedforward mechanisms stimulated by engaging with social cognition training. This will be investigated by examining the impact of social cognition training on plasma levels. We also directly administer OT in-order to amplify biological and cognitive markers that facilitate improvements in social-functioning.

Hypotheses
Following SCT treatment, individuals with early psychosis in the SCT + OT + TAU condition compared to SCT + Placebo + TAU condition will demonstrate:

Outcome Hypothesis
1. Significant improvement on measures of social cognition and social function.

Mechanism Hypothesis
1. OT administration will enhance social-cognitive and biological markers compared to the placebo condition.
2. OT administration will enhance social functioning outcomes following SCT training compared to the placebo group.
3. Changes in biological and social-cognitive markers in both the OT and Placebo SCT groups will predict improvements in social functioning. This association will be stronger in the OT condition given the influence of OT on critical markers will be amplified.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 33657 0
Prof Adam Guastella
Address 33657 0
100 Mallett St
Camperdown, 2050
Country 33657 0
Australia
Phone 33657 0
+61 2 93510539
Fax 33657 0
Email 33657 0
adam.guastella@sydney.edu.au
Contact person for public queries
Name 16904 0
Ms Cristina Cacciotti Saija
Address 16904 0
Brain and Mind Research Institute, The University of Sydney
100 Mallett St, Camperdown
NSW 2050
Country 16904 0
Australia
Phone 16904 0
+61 2 9351 0799
Fax 16904 0
+61 2 9351 0731
Email 16904 0
cristina.cacciottisaija@sydney.edu.au
Contact person for scientific queries
Name 7832 0
A/Prof Associate Professor Adam Guastella
Address 7832 0
Brain and Mind Research Institute, The University of Sydney
100 Mallett St, Camperdown
NSW 2050
Country 7832 0
Australia
Phone 7832 0
+61 2 9351 0799
Fax 7832 0
+61 2 9351 0731
Email 7832 0
adam.guastella@sydney.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary