SchizophreniaSINAPPS-1NCT02449746
Study of Immunotherapy in Autoantibody Positive Psychosis
A study testing Plasma Exchange and Intravenous immunoglobulin in people with Schizophrenia and Psychosis, run by University of Cambridge at 5 sites in United Kingdom.
Trial summary
Psychosis is a mental health problem that causes people to perceive or interpret things differently from those around them, often involving hallucinations or delusions. Psychosis and schizophrenia are common disorders which predominantly affect younger adults. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Schizophrenia, Psychosis, Auto Immune Disorders
- What is being tested?
- Plasma Exchange and Intravenous immunoglobulin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 5 sitesUnited Kingdom
- Study dates
- Aug 2015to Dec 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Acute psychosis
- Serum and/or Cerebrospinal flud (CSF) neuronal membrane autoantibodies (including N-methyl-D-aspartate receptor (NMDAR), Voltage gated potassium channel (VGKC), Leucine-rich, glioma inactivated 1,(LGI1), gamma-aminobutyric acid (GABA [A]) receptor)
- Positive and Negative Syndrome Scale (PANSS) >4 on items of positive psychotic symptoms
Who cannot join
- current symptoms greater than 2 years duration,
- co-existing severe neurological disease
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United Kingdom5 sites
University Hospitals Birmingham
Birmingham
Cambridge University Hospitals
Cambridge
Nottingham University Hospitals
Nottingham
Oxford University Hospitals
Oxford
University Hospitals Southampton
Southampton
About this study
Official title: An Unblinded Study of the Feasibility of Plasmapheresis or Intravenous Immunoglobulin, Combined With Corticosteroids, in Patients With Acute Psychosis Associated With Anti-neuronal Membrane Auto-antibodies
Psychosis is a mental health problem that causes people to perceive or interpret things differently from those around them, often involving hallucinations or delusions. Psychosis and schizophrenia are common disorders which predominantly affect younger adults. Recently, the investigators discovered that 5-10% of people with psychosis have antibodies in the blood that are capable of targeting the surface of brain cells, specific to the N-methyl-D-aspartate (NMDA) receptor or voltage gated potassium channel complex, which the investigators believe may be causing the problem. Those positive for antibodies may have a problem with their immune system and this may prevent their brain from working normally. This trial aims to test the feasibility of removing or reducing the antibodies in patients' blood, using immunotherapy, and see if this improves symptoms of psychosis. Immunotherapy in this feasibility study will involve giving all patients steroid tablets and half of them will also receive a drug called "intravenous immunoglobulin" whereas the other half will have a procedure called "plasma exchange". The feasibility study is designed to identify which method of immunotherapy is most suitable for use in this patient population.
Results from this will inform on the methodology used for a proposed larger randomised control trial.
Read the detailed description
An autoimmune disease occurs when a person's immune system begins to respond to normal bodily substances and tissues as if it were foreign or related to disease. There are a number of autoimmune disorders, some of which can affect the brain by targeting the surface of brain cells, for example signalling proteins like the NMDA receptor or voltage gated potassium channel complex. Some cases of encephalitis, a disorder of brain inflammation that can be autoimmune, are caused by these antibodies, but often present with psychotic experiences, such as hallucinations, and may see a psychiatrist at this stage, before they go on to experience seizures and brain swelling, and are seen by a neurologist. These patients are treated with immunotherapy, and after treatment see a reduction in both seizures and psychotic symptoms.
Recently the investigators identified patients with psychosis who test positive for these antibodies, but do not go on to experience these other symptoms of encephalitis. It has been suggested that these patients suffer from an autoimmune disorder similar to the encephalitis described above. Small pilot studies in these antibody positive psychosis patients have shown various immunotherapies can reduce both symptoms of psychosis and number of autoantibodies present in their blood. A randomised clinical trial (RCT) is required to confirm this. However a feasibility study is required first to investigate whether it is possible to deliver the immunotherapy treatments in patients with psychosis. The treatments require an infusion over a few hours (IVIG) or an admission to an acute medical ward for several days(plasma exchange). Both may be challenging for people who are paranoid or agitated. The investigators need to assess whether it is possible to deliver these treatments before proceeding to a large scale, clinical trial.
This is a multicentre, randomised, uncontrolled, open label feasibility study. Patients with psychosis and a positive blood test for antibodies will be identified from one of 24 recruiting centres across England. They will undergo screening assessment for eligibility (interview with psychiatrist and neurologist and baseline investigations where possible, including MRI, EEG and lumbar puncture) and give informed consent for the study. A further blood sample (10ml) will be taken for future research. 10 Participants will be randomised to one of two clinical care pathways: either an infusion of intravenous immunoglobulins, or plasma exchange treatment. Both groups will receive steroid tablets, and both groups will continue to receive psychiatric treatment, including antipsychotic medication, as normal.
At two months after randomisation the research team will speak to the treating clinicians to gather the primary outcome measure which is whether the patient received the allocated treatment within two weeks of allocation. The researchers may also confirm this outcome from the clinical records.
- Conditions
- Schizophrenia, Psychosis, Auto Immune Disorders
- Being tested
- Plasma Exchange, Intravenous immunoglobulin
- Keywords
- Schizophrenia, Psychosis, Mental Health, Autoimmunity, Psychoneuroimmunology
- Medical subject headings
- Schizophrenia, Psychotic Disorders, Psychological Well-Being, Autoimmune Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Plasma ExchangeBiological
Also called PLEX
PLEX is a procedure in which the subject's blood is passed through a medical device which separates out plasma from the other blood components, and replaces the plasma with albumin or plasma or other colloid. PLEX therefore removes circulating pathogenic antibodies, and furthermore therapeutic benefit after PLEX supports an antibody mediated pathogenesis of disease. In PLEX, 200-250 mL plasma per kg body weight is exchanged typically over 7-14 days using 5% albumin as replacement, often at alternate days which increases the amount of immunoglobulin removed due to equilibrium effects. PLEX modality (centrifugation or filtration), type of anticoagulation, and dose scheduling will be determined by local centre practice.
Intravenous immunoglobulinBiological
Also called IVIG
Active Comparator: Intravenous Immunoglobulin (IVIG) IVIG is a pooled blood product from 3000-100,000 human blood donors with direct immunomodulatory effects.
IVIG will be given at a dose of 2g/kg over 4 days. Dosing at 2g/kg is established in neurological disorders, with limited evidence that lower doses are less effective although adequate dosing studies have not been performed.
| Study group | Role | What they receive |
|---|---|---|
| Intravenous Immunoglobulin (IVIG) | Active comparator | Intravenous Immunoglobulin IVIG is a pooled blood product from 3000-100,000 human blood donors with direct immunomodulatory effects.
IVIG will be given at a dose of 2g/kg over 4 days. Dosing at 2g/kg is established in neurological disorders, with limited evidence that lower doses are less effective although adequate dosing studies have not been performed. Receives: Biological: Intravenous immunoglobulin |
| Plasma Pheresis / Plasma Exchange (PLEX) | Active comparator | Plasma Exchange (PLEX) is a procedure in which the subject's blood is passed through a medical device which separates out plasma from the other blood components, and replaces the plasma with albumin or plasma or other colloid. PLEX therefore removes circulating pathogenic antibodies, and its use was first reported in myasthenia gravis in 1976, and furthermore therapeutic benefit after PLEX supports an antibody mediated pathogenesis of disease. In PLEX, 200-250 mL plasma per kg body weight is exchanged typically over 7-14 days using 5% albumin as replacement, often at alternate days which increases the amount of immunoglobulin removed due to equilibrium effects . PLEX modality (centrifugation or filtration), type of anticoagulation, and dose scheduling will be determined by local centre practice Receives: Biological: Plasma Exchange |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of patients who start on allocated care pathway within 2 weeks of randomisation.
percentage of recruited patients who start on allocated care pathway within 2 week from randomisation
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2015 (estimated)
- Study startAug 2015
- Primary completionAug 2017
- Study completionDec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cambridge
- Sponsor type
- University, hospital or other
- Collaborators
- University of Oxford, Stanley Medical Research Institute, McPin Foundation
- Responsible party
- Principal investigator, Alasdair Coles, University of Cambridge
- Investigators
- Alasdair Coles, 01223 762016, Principal investigator, ajc1020@medschl.cam.ac.uk
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02449746
- Sponsor's protocol ID
- 609/M/C/1368
- Acronym
- SINAPPS-1
- Status last verified
- Feb 2018
- First submitted
- 13 May 2015
- Last updated
- 19 Feb 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Unblinded Study of the Feasibility of Plasmapheresis or Intravenous Immunoglobulin, Combined With Corticosteroids, in Patients With Acute Psychosis Associated With Anti-neuronal Membrane Auto-antibodies
- ClinicalTrials.gov ID
- NCT02449746
- Acronym / sponsor ID
- SINAPPS-1 / 609/M/C/1368
- Conditions
- Schizophrenia, Psychosis, Auto Immune Disorders
- Keywords
- Schizophrenia, Psychosis, Mental Health, Autoimmunity, Psychoneuroimmunology
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of CambridgeUniversity, hospital or other
- Collaborators
- University of Oxford, Stanley Medical Research Institute, McPin Foundation
- Study start
- Aug 2015 (actual)
- Primary completion
- Aug 2017 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 20 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Psychosis is a mental health problem that causes people to perceive or interpret things differently from those around them, often involving hallucinations or delusions. Psychosis and schizophrenia are common disorders which predominantly affect younger adults. Recently, the investigators discovered that 5-10% of people with psychosis have antibodies in the blood that are capable of targeting the surface of brain cells, specific to the N-methyl-D-aspartate (NMDA) receptor or voltage gated potassium channel complex, which the investigators believe may be causing the problem. Those positive for antibodies may have a problem with their immune system and this may prevent their brain from working normally. This trial aims to test the feasibility of removing or reducing the antibodies in patients' blood, using immunotherapy, and see if this improves symptoms of psychosis. Immunotherapy in this feasibility study will involve giving all patients steroid tablets and half of them will also receive a drug called "intravenous immunoglobulin" whereas the other half will have a procedure called "plasma exchange". The feasibility study is designed to identify which method of immunotherapy is most suitable for use in this patient population.
Results from this will inform on the methodology used for a proposed larger randomised control trial.
Detailed description
An autoimmune disease occurs when a person's immune system begins to respond to normal bodily substances and tissues as if it were foreign or related to disease. There are a number of autoimmune disorders, some of which can affect the brain by targeting the surface of brain cells, for example signalling proteins like the NMDA receptor or voltage gated potassium channel complex. Some cases of encephalitis, a disorder of brain inflammation that can be autoimmune, are caused by these antibodies, but often present with psychotic experiences, such as hallucinations, and may see a psychiatrist at this stage, before they go on to experience seizures and brain swelling, and are seen by a neurologist. These patients are treated with immunotherapy, and after treatment see a reduction in both seizures and psychotic symptoms.
Recently the investigators identified patients with psychosis who test positive for these antibodies, but do not go on to experience these other symptoms of encephalitis. It has been suggested that these patients suffer from an autoimmune disorder similar to the encephalitis described above. Small pilot studies in these antibody positive psychosis patients have shown various immunotherapies can reduce both symptoms of psychosis and number of autoantibodies present in their blood. A randomised clinical trial (RCT) is required to confirm this. However a feasibility study is required first to investigate whether it is possible to deliver the immunotherapy treatments in patients with psychosis. The treatments require an infusion over a few hours (IVIG) or an admission to an acute medical ward for several days(plasma exchange). Both may be challenging for people who are paranoid or agitated. The investigators need to assess whether it is possible to deliver these treatments before proceeding to a large scale, clinical trial.
This is a multicentre, randomised, uncontrolled, open label feasibility study. Patients with psychosis and a positive blood test for antibodies will be identified from one of 24 recruiting centres across England. They will undergo screening assessment for eligibility (interview with psychiatrist and neurologist and baseline investigations where possible, including MRI, EEG and lumbar puncture) and give informed consent for the study. A further blood sample (10ml) will be taken for future research. 10 Participants will be randomised to one of two clinical care pathways: either an infusion of intravenous immunoglobulins, or plasma exchange treatment. Both groups will receive steroid tablets, and both groups will continue to receive psychiatric treatment, including antipsychotic medication, as normal.
At two months after randomisation the research team will speak to the treating clinicians to gather the primary outcome measure which is whether the patient received the allocated treatment within two weeks of allocation. The researchers may also confirm this outcome from the clinical records.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intravenous Immunoglobulin (IVIG) | Active comparator | Biological: Intravenous immunoglobulinIntravenous Immunoglobulin IVIG is a pooled blood product from 3000-100,000 human blood donors with direct immunomodulatory effects. IVIG will be given at a dose of 2g/kg over 4 days. Dosing at 2g/kg is established in neurological disorders, with limited evidence that lower doses are less effective although adequate dosing studies have not been performed. |
| Plasma Pheresis / Plasma Exchange (PLEX) | Active comparator | Biological: Plasma ExchangePlasma Exchange (PLEX) is a procedure in which the subject's blood is passed through a medical device which separates out plasma from the other blood components, and replaces the plasma with albumin or plasma or other colloid. PLEX therefore removes circulating pathogenic antibodies, and its use was first reported in myasthenia gravis in 1976, and furthermore therapeutic benefit after PLEX supports an antibody mediated pathogenesis of disease. In PLEX, 200-250 mL plasma per kg body weight is exchanged typically over 7-14 days using 5% albumin as replacement, often at alternate days which increases the amount of immunoglobulin removed due to equilibrium effects . PLEX modality (centrifugation or filtration), type of anticoagulation, and dose scheduling will be determined by local centre practice |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Acute psychosis
- Serum and/or Cerebrospinal flud (CSF) neuronal membrane autoantibodies (including N-methyl-D-aspartate receptor (NMDAR), Voltage gated potassium channel (VGKC), Leucine-rich, glioma inactivated 1,(LGI1), gamma-aminobutyric acid (GABA [A]) receptor)
- Positive and Negative Syndrome Scale (PANSS) >4 on items of positive psychotic symptoms
Key exclusion criteria (2 listed)
- current symptoms greater than 2 years duration,
- co-existing severe neurological disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Plasma ExchangeAlso: PLEXPLEX is a procedure in which the subject's blood is passed through a medical device which separates out plasma from the other blood components, and replaces the plasma with albumin or plasma or other colloid. PLEX therefore removes circulating pathogenic antibodies, and furthermore therapeutic benefit after PLEX supports an antibody mediated pathogenesis of disease. In PLEX, 200-250 mL plasma per kg body weight is exchanged typically over 7-14 days using 5% albumin as replacement, often at alternate days which increases the amount of immunoglobulin removed due to equilibrium effects. PLEX modality (centrifugation or filtration), type of anticoagulation, and dose scheduling will be determined by local centre practice. | Biological | Plasma Pheresis / Plasma Exchange (PLEX) |
| Intravenous immunoglobulinAlso: IVIGActive Comparator: Intravenous Immunoglobulin (IVIG) IVIG is a pooled blood product from 3000-100,000 human blood donors with direct immunomodulatory effects. IVIG will be given at a dose of 2g/kg over 4 days. Dosing at 2g/kg is established in neurological disorders, with limited evidence that lower doses are less effective although adequate dosing studies have not been performed. | Biological | Intravenous Immunoglobulin (IVIG) |
Primary outcome
Percentage of patients who start on allocated care pathway within 2 weeks of randomisation.
Time frame: 2 weeks
percentage of recruited patients who start on allocated care pathway within 2 week from randomisation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alasdair Coles, 01223 762016 principal investigator
ajc1020@medschl.cam.ac.uk
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Plasma Exchange and Intravenous immunoglobulin in people with Schizophrenia and Psychosis, run by University of Cambridge at 5 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of patients who start on allocated care pathway within 2 weeks of randomisation. (time frame: 2 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2018.