1805628 / A randomised phase II double-blinded placebo-controlled trial of intravenous immunoglobulins and rituximab in patients with antibody-associated psychosis (SINAPPS2)
Psychosis and schizophrenia are caused by factors associated with excess dopamine and abnormally low N-methyl D-aspartate receptor (NMDAR) functioning. There is increasing evidence for the role of inflammation in these disorders. We propose that one possible cause of psychosis and schizophrenia is the presence of antibodies in the blood that bind to the neuronal membrane in the brain. Since discovery of antibodies that bind to the NMDAR (NMDAR-ab) that cause encephalitis, we have discovered NMDAR-ab or voltage-gated potassium channel complex antibodies (VGKC-ab) in 6.5% of first episode psychosis (FEP) patients, without signs of encephalitis. This was replicated in an on-going MRC-funded study, where 8.8% of FEP patients possessed these autoantibodies.
Open-label experience suggests immunotherapy is effective in cases of full antibody-encephalitis. We recently reported on 18 patients with NMDAR-ab; 9 resolved on their own, or responded to antipsychotics, and 9 were resistant to up to 3 antipsychotics. Antipsychotic resistant patients were treated with corticosteroids alongside immunotherapy (plasma exchange (PLEX) or intravenous immunoglobulin (IVIG; a blood product containing antibodies), with subsequent mycophenolate or rituximab treatment), and responded well.
Informed by our feasibility study, this randomised double-blinded placebo-controlled trial aims to test the hypothesis that immunotherapy is an effective treatment for antibody-associated psychosis, either in FEP or relapse following remission, alongside antipsychotic medication if required. Trial immunotherapy consists of IVIG
(2g/kg over 4 days) followed by two infusions of 1g rituximab(~day 30, then 14 days after the first infusion). This trial combines a rapid-action treatment (IVIG) to induce symptom remission, with a longer-action therapy (rituximab) to maintain remission.
Before treatment, a number of assessments will be performed, including physician review and examination, laboratory investigations (including Ab-assays and safety blood tests and storing serum for future research), as well as clinical and cognitive assessments. (Study due to close 31/12/2021)
1805635 / The HOME Study
NHS general hospitals have more than two million unplanned admissions of people aged 65 and older every year. These patients typically spend more time in hospital than those aged under 65. Long hospital stays are bad for older patients: they can get new illnesses like infections and lose their independence. They are also bad for the NHS which has a shortage of hospital beds. Psychological problems, like dementia, confusion, depression and anxiety, are common in older patients and these are an important cause of long hospital stays. These problems are often not identified in busy hospital wards where the focus is on patients’ physical illnesses.
In this study, we will research whether adding a new approach (sometimes called Proactive Liaison Psychiatry) to the identification and management of psychological problems reduces the time that older people spend in acute general hospital wards.
We will recruit approximately 3,588 patients aged 65 and older, who have been admitted to acute wards in hospitals in Oxfordshire, Cambridgeshire and Devon. They will be randomly allocated to receive usual care, or usual care plus the new approach (which will involve seeing a doctor, nurse or occupational therapist who specialises in psychological problems in the medically ill). We will study whether the new approach reduces the time that patients spend in hospital and whether it improves their quality of life and independence. We will also interview patients, carers and healthcare professionals to learn about their experiences of the new approach.
The study is funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research programme. (Study due to close 31/12/2018)