How does oxytocin affect brain functioning in people at high risk of developing psychosis?

ISRCTN	ISRCTN48799530
DOI	https://doi.org/10.1186/ISRCTN48799530
IRAS number	150687
Secondary identifying numbers	CPMS 18011, IRAS 150687

Submission date: 15/03/2023
Registration date: 17/03/2023
Last edited: 03/04/2023

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Mental and Behavioural Disorders

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Psychotic disorders are usually preceded by a prodromal phase, called the Ultra High-Risk Mental State (UHR), characterised by attenuated psychotic symptoms, emotional dysregulation and difficulties with interpersonal relationships. Emotional and social cognition problems are common in UHR individuals, are the main source of their distress, and are a key factor in the associated loss of vocational function. Administration of oxytocin (OT) appears to promote social interactions and emotional bonding in healthy volunteers, improve emotional and social dysfunction, and ameliorate psychotic symptoms in patients with schizophrenia. The present study will evaluate the mechanism of action of OT on social cognition and emotional processing in UHR individuals.

Who can participate?
Adults aged 18-35 who are UHR for psychosis.

What does the study involve?
During each OT/placebo challenge, the team will use magnetic resonance imaging (MRI) to measure the effects of OT on the neural substrates of emotional processing and social cognition. Subjects will also undergo a clinical assessment with standardized psychometric scales.

What are the possible benefits and risks of participating?
Participants will not benefit directly but the potential findings from the research may improve understanding of the neurobiological factors underlying psychosis. The experimental treatment will not interfere with the standard care of the participants. OT has been widely used for several years in medicine. A review of 38 studies conducted since 1990 with a total of 1529 participants indicated that 18-40 IU OT is safe. There is a risk that some participants may feel anxious or claustrophobic during MRI scanning.

Where is the study run from?
Department of Psychosis Studies at the Institute of Psychiatry, Psychology and Neuroscience, King’s College, London (UK)

When is the study starting and how long is it expected to run for?
January 2014 until October 2017

Who is funding the study?
1. National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust and King’s College London
2. Brain & Behaviour Research Foundation National Alliance for Research on Schizophrenia & Depression (NARSAD) Award

Who is the main contact?
Prof Paolo Fusar-Poli, paolo.fusar-poli@kcl.ac.uk (UK)

Contact information

Prof Paolo Fusar-Poli
Principal Investigator

Early Psychosis: Interventions & Clinical-detection (EPIC) Lab
Department of Psychosis Studies
5th Floor, Institute of Psychiatry
Psychology & Neuroscience
King’s College London
16 De Crespigny Park
London
SE5 8AF
United Kingdom

ORCID ID	0000-0003-3582-6788
Phone	None provided
Email	paolo.fusar-poli@kcl.ac.uk

Study information

Study design	Randomized interventional study
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Community
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	Neurophysiological basis of effects of oxytocin on emotional processing and social cognition in people at ultra-high risk for psychosis.
Study objectives	The primary outcome measure is to investigate the regional brain response under oxytocin challenge (versus placebo) in subjects at ultra-high risk (UHR) for psychosis. Specifically, we hypothesise that a single dose of oxytocin modulates brain functioning during emotional processing and social cognition in UHR subjects.
Ethics approval(s)	Approved 12/11/2014, London – London Bridge Research Ethics Committee (Research Ethics Committee London Centre, Ground Floor, Skipton House, 80 London Road, London, SE1 6LH, UK; +44 (0)207 1048 387, (0)207 1048 124; londonbridge.rec@hra.nhs.uk), ref: 14/LO/1692
Health condition(s) or problem(s) studied	Schizophrenia, schizotypal and delusional disorders
Intervention	This is a randomised, double-blind, 40 IU intranasal oxytocin versus placebo single-dose challenge with a crossover design (1-week washout). Oxytocin administration will follow international guidelines (Guastella AJ et al., Recommendations for the standardisation of oxytocin nasal administration and guidelines for its reporting in human research) and be conducted under researcher supervision. During each challenge, subjects will undergo a 90-minute MRI scan which includes fMRI tasks exploring social cognition, arterial spin labelling, resting-state fMRI, and MR-spectroscopy.
Intervention type	Biological/Vaccine
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Oxytocin
Primary outcome measure	Regional brain response to oxytocin versus placebo challenge in subjects at ultra-high risk (UHR) for psychosis measured using MRI, which includes fMRI tasks of social cognition and other neuroimaging readouts (arterial spin labelling, resting-state fMRI, and MR-spectroscopy), during the challenge
Secondary outcome measures	The are no secondary outcome measures
Overall study start date	01/01/2014
Completion date	17/10/2017

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Male
Target number of participants	Planned Sample Size: 30; UK Sample Size: 30
Total final enrolment	30
Key inclusion criteria	Among the new referrals to the OASIS service, South London and Maudsley NHS Foundation Trust, we will enroll those meeting inclusion criteria for a UHR state for psychosis (as defined on the CAARMS revised version questionnaire).
Key exclusion criteria	1. Personal history of psychotic illness (i.e. schizophrenia, schizoaffective disorder or related psychosis) 2. Aged below 18 years old 3. Aged over 35 years old 4. Significant cognitive deficit (IQ<60 as measured by the shortened WAIS) 5. Significant history of drug or alcohol misuse or dependence 6. Severe neurological and medical conditions 7. Evidence of hyponatremia in participant's recent blood test 8. Rejection of informed consent 9. Pregnancy (apply to women of childbearing age) 10. Breastfeeding (applies to women of childbearing age) 11. Non-use of contraceptive methods (apply to women of childbearing age).
Date of first enrolment	06/05/2015
Date of final enrolment	10/10/2017

Locations

Countries of recruitment

England
United Kingdom

Study participating centres

Kings College London

Strand
London
WC2R 2LS
United Kingdom

Maudsley Hospital

Denmark Hill
London
SE5 8AZ
United Kingdom

Kings College Hospital

Mapother House
De Crespigny Park
Denmark Hill
London
SE5 8AB
United Kingdom

East London NHS Foundation Trust

Robert Dolan House
9 Alie Street
London
E1 8DE
United Kingdom

Sponsor information

King's College London
University/education

C/o: Barbara Dahill
1.8 Hodgkin Building
London
SE1 4UL
England
United Kingdom

Phone	+44 (0)2078486960
Email	Barbara.dahill@kcl.ac.uk
Website	http://www.kcl.ac.uk/index.aspx
"ROR"	https://ror.org/0220mzb33

South London and Maudsley NHS Foundation Trust
Hospital/treatment centre

C/o: Jennifer Leibscher
Institute of Psychiatry
De Crespigny Park
London
SE5 8AF
England
United Kingdom

Phone	+44 (0)2078480251
Email	jennifer.leibscher@kcl.ac.uk
Website	http://www.slam.nhs.uk/
"ROR"	https://ror.org/015803449

Funders

Funder type

Government

National Institute for Health and Care Research
Government organisation / National government

Alternative name(s): National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
Location: United Kingdom

Brain and Behavior Research Foundation
Government organisation / Trusts, charities, foundations (both public and private)

Alternative name(s): Brain & Behavior Research Foundation, The Brain & Behavior Research Foundation, Brain & Behavior Research FDN, The Brain and Behavior Research Foundation, BBRFoundation, National Alliance for Research on Schizophrenia & Depression, NATIONAL ALLIANCE FOR RESEARCH ON SCHIZOPHRENIA AND DEPRESSION, National Alliance for Research on Schizophrenia and Depression, Inc., BBRF, NARSAD
Location: United States of America

Results and Publications

Intention to publish date	09/01/2019
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
Publication and dissemination plan	Planned publication in a high-impact peer reviewed journal
IPD sharing plan	The datasets generated during and/or analysed during the current study are not expected to be made available. Individual-level data are not currently openly available due to data privacy, ongoing research and regulatory/ethical approvals. However, aggregate (group-level) clinical, demographic and imaging data may be made available, upon request (at the investigator’s discretion) via contact with Prof Fusar-Poli, paolo.fusar-poli@kcl.ac.uk. Aggregate data have already been shared with, for example, the ENIGMA Clinical High-Risk Working Group for the purposes of large-scale cross-site meta- and mega-analysis.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Other publications	Intranasal oxytocin increases heart-rate variability in men at clinical high risk for psychosis: a proof-of-concept study	12/07/2020	15/03/2023	Yes	No
Results article	Oxytocin modulates hippocampal perfusion	09/01/2019	15/03/2023	Yes	No
Results article	Oxytocin on brain activation during inferring others’ beliefs and social emotions	22/06/2020	15/03/2023	Yes	No
Results article	Oxytocin on glutamate and other metabolites	28/03/2019	15/03/2023	Yes	No
HRA research summary			28/06/2023	No	No

Editorial Notes

03/04/2023: Internal review.
15/03/2023: Trial's existence confirmed by National Institute for Health and Care Research (NIHR) (UK).