Early Psychosis Research Group

SELECTED RESEARCH PROJECTS

A randomised phase II double-blinded placebo-controlled trial of intravenous immunoglobulins and rituximab in patients with antibody-associated psychosis (SINAPPS2)

We have found  that some people with psychosis have particular antibodies that are known to cause another serious brain disorder - encephalitis.  It is possible that these same antibodies are also causing psychosis in some people, and we are undertaking research to establish whether this is the case.

We undertake clinical trials of immune therapies in people with psychosis, and experimental medicine studies to examine the interaction between the immune system and the brain.

We propose that in some patients the cause of psychosis may be antibodies binding to neuronal membrane targets (NMDAR, LGI1, GABA-A and other), especially NMDA receptors, in the brain. The hypothesis underlying the SINAPPS2 trial is that these antibodies may be pathogenic and responsible for isolated psychosis (antibody-associated psychosis).

We are currently conducting the SINAPPS2 trial to test whether immunotherapy is an effective treatment for antibody-associated psychosis. It is a randomised phase II double-blinded placebo-controlled trial of intravenous immunoglobulin and rituximab in patients with psychosis and anti-neuronal membrane antibody. Patents (16-60 years old) with antibody-associated psychosis are invited to one of the NHS hospitals participating in the study, where they are assessed and assisted by a team of SINAPPS2 clinicians and researchers. Eligible patients are randomly allocated to receive either intravenous immunoglobulin combined with rituximab or placebo treatment and they will be followed for at least 12 months.

 Contact: sinapps@psych.ox.ac.uk

EXTEND: pERSONALISED cARE FOR eARLY PSYCHOSIS

Early Intervention in Psychosis (EIP) services are phase-specific community mental health teams that treat people with First Episode Psychosis (FEP). Currently, EIP services are time-limited to 3 years, the rationale being that early intensive treatment will preclude the need for ongoing care. It is not known what the optimal length of EIP treatment should be. People with FEP can have diverse illness trajectories, meaning an eventual outcome is not easy to predict. Some people may benefit from longer treatment. Alternatively, delivery of specific treatments may be more important than the overall duration of EIP, which could therefore be delivered in a shorter timeframe. 

The EXTEND study  is aimed determining whether a flexible, needs-focussed duration of EIP treatment could be used as an alternative to the current time-limited service.The study comprises a team of researchers from universities across the UK, led by Professor Belinda Lennox from the University of Oxford and Professor Paul French from Manchester Metropolitan University. The EXTEND Study is funded in full by the National Institute for Health and Care Research (NIHR), as part of their Programme Grants for Applied Research.

Contact: extend@psych.ox.ac.uk 

Early Psychosis multi-arm, multi-stage (MAMS) platform trial: PUMA

With lived-experience involvement being central to their design and implementation, multi-arm multi-stage (MAMS) trials have revolutionised clinical trials methodology, updated standard-of-care and resulted in improved patient outcomes in many illnesses. As mechanistically-based experiments they also illuminate underlying biology.

The PUMA project aims a similar transformation for the treatment of early psychosis. Wellcome has approved funding for the 30-month design and set-up phase of an adaptive Randomised Control Trials platform for early psychosis, the first time this kind of design has been applied in mental health. This will allow testing of new treatment options in a much faster and more efficient way to accelerate hopefully the development of new effective and safe treatments and transform the care for patients with early psychosis. Interventions prioritised through a systematic process (beginning with drugs but not restricted to them) will be evaluated in an established trial platform (based in English Early Psychosis Services) according to a priori statistical rules that mean intervention arms that are going to fail will be closed, allowing the platform to move on to test further prioritised options.  This 10-minute video gives a very good explanation of what MAMS trial platforms are.

Over the 30-month design and set-up phase we will design the trial platform, producing a trial protocol and the necessary infrastructure ready to be implemented. We will involve patients, carers and clinicians across the country to design all aspects of this trial platform, ensuring that it is meaningful for patients and deliverable within UK services. We will select a hub and chief investigator for the platform and establish a national network of research sites. Our aim is to establish an infrastructure to enable the rapid trialling of new treatments in early psychosis.

Success will depend crucially on effective lived-experience input to cleverly designed processes that will support high levels of recruitment to trials that matter. MQ’s partnership will have a key role in PUMA’s success. We will have insights from the patients and carers throughout the project, for instance, to decide what should be the eligibility criteria for trial participants; how long the trials should be; what should be the outcome measures in psychosis trials; how to make the recruitment processes and participation in trials more appropriate; how to reach out to communities of patients who are often not included in trials; how to involve patients who don’t speak English; and so on.

The project aims will be achieved through five working groups (WG) (Trial Design WG, Treatment Recommendation WG, Outcome Measures WG, Patient and Carers Engagement WG, and Infrastructure WG) discussing such questions.  Each working group will have patient and carer representatives within their membership. There will also be a separate working group only consisting of patients and carers and MQ representatives to reflect on activities across the whole project. 

Contact: ksenija.yeeles@psych.ox.ac.uk

PREVIOUS STUDIES

Oxford Predicting Outcome in First Episode Psychosis (OX-POP)

The impact of psychotic illness on an individual's quality of life can be debilitating and life limiting, and psychotic illnesses are large contributors to the global burden of disease.  Over the last 20 years, a new approach called Early Intervention in Psychosis (EIP) services have been developed to treat people who are experiencing their first episode of psychosis.  EIP services are now the gold-standard treatment for early psychosis throughout the world. 

EIP services are time-limited, which means that after two or three years individuals are transferred back to primary care or standard adult mental health services.  We know that individuals can have vastly different illness trajectories following first episode of psychosis, yet there is little research into the immediate and long-term outcomes of people after they leave EIP, their interaction with health services and measuring, predicting and validating clinical decision making tools to help determine poor outcomes to this group of individuals.

 Contact:  stephen.puntis@psych.ox.ac.uk

Neuronal Antibodies and Electrophysiology

We are investigating ways in which Electroencephalography (EEG) can be used to improve diagnosis and work out the best treatments for individuals with psychosis.  EEG is a safe, non-invasive test which is used routinely in the NHS for other disorders.  It involves placing sensors on the scalp which can detect the faint electoral signals coming from the brain.  in particular, we are trying to find out whether there are differences between the EEG recordings made from people with psychosis who have antibodies to brain chemicals compared with those who do not.  If we find that there are such differences, it will help to decide which people with psychosis will benefit from immune suppressant treatment.

 Contact:naeeg@psych.ox.ac.uk