PsychosisPhase 2SINAPPS2NCT03194815
IVIG and Rituximab in Antibody-associated Psychosis - SINAPPS2
A Phase 2 study testing Intravenous immunoglobulin and Rituximab in people with Psychosis and Autoimmune Encephalitis, run by University of Cambridge at 10 sites in United Kingdom.
Trial summary
A randomised phase II double-blinded placebo-controlled trial designed to explore the utility of immunotherapy for patients with acute psychosis associated with anti-neuronal membranes (NMDA-receptor or Voltage Gated Potassium Channel). Read more about this study
- Who is it for?
- Ages 16 to 70 years
- Conditions the study is for
- Psychosis, Autoimmune Encephalitis
- What is being tested?
- Intravenous immunoglobulin and Rituximab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 10 sitesUnited Kingdom
- Study dates
- 1 Nov 2017to 30 Apr 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 16 to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Acute psychosis >2 weeks. This may either be first episode or relapse after remission (remission defined as having mild or absent symptoms of psychosis for at least 6 months)
- Serum or CSF neuronal membrane autoantibodies at pathological levels (including NMDAR, LGI1 and other)
- Psychosis symptoms as defined by PANSS ≥4 on at least one of the following items: P1, P2, P3, N1, N4, N6, G5 and G9.
Who cannot join
- Current episode of psychosis greater than 24 months duration
- Co-existing severe neurological disease
- Evidence of current acute encephalopathy
- Hepatitis or HIV infection, pregnancy
- Contraindications to any trial drug
- Concurrent enrolment in another CTIMP
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United Kingdom10 sites
Cambridge University Hospitals NH Foundation Trust
Cambridge
Royal Devon and Exeter NHS Foundation Trust
Exeter
NHS Greater Glasgow and Clyde
Glasgow
The Walton Centre NHS Foundation Trust
Liverpool
University College London Hospitals Nhs Foundation Trust
London, NW1 2PG
King's College Hospital NHS Foundation Trust
London
Salford Royal NHS Foundation Trust
Manchester
Nottingham University Hospitals NHS Trust
Nottingham
Oxford University Hospitals NHS Foundation Trust
Oxford
Sheffield Teaching Hospitals NHS Foundation Trust
Sheffield
About this study
Official title: A Randomised Phase II Double-blinded Placebo-controlled Trial of Intravenous Immunoglobulins and Rituximab in Patients With Antibody-associated Psychosis (SINAPPS2)
A randomised phase II double-blinded placebo-controlled trial designed to explore the utility of immunotherapy for patients with acute psychosis associated with anti-neuronal membranes (NMDA-receptor or Voltage Gated Potassium Channel).
Primary objective: To test the efficacy of immunotherapy (IVIG and rituximab) for patients with acute psychosis associated with anti-neuronal membranes.
Secondary objective: To test safety of immunotherapy (IVIG and rituximab) for patients with acute psychosis associated with anti-neuronal membranes.
Read the detailed description
Investigators propose a randomised double-blinded placebo-controlled trial to test the hypothesis that immunotherapy is an effective treatment of antibody-associated psychosis, either first episode of psychosis or relapse following previous remission. Immunotherapy for the trial consists of one cycle of intravenous immunoglobulin (IVIG: 2g/kg over days 1-4) followed by two infusions of 1g rituximab (at day 28-35, and then 14 days after the first infusion). The rationale for this regime is that it combines a rapid-action treatment (IVIG) to induce remission with a longer-action therapy (rituximab) to maintain remission. It is based on a protocol where elimination of circulating antibodies is the treatment goal, namely "desensitisation" of potential transplant patients who have multiple anti-HLA antibodies capable of inducing hyperacute rejection and also being tested in various trials on clinicaltrials.gov (NCT00642655, NCT01178216, and NCT01502267). Blinding is required to minimise placebo responses in a trial based on symptomatology.
- Conditions
- Psychosis, Autoimmune Encephalitis
- Being tested
- Intravenous immunoglobulin, Placebo, Rituximab
- Keywords
- Psychosis, Immunotherapy, Autoantibodies
- Medical subject headings
- Psychotic Disorders, Autoimmune Diseases of the Nervous System
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous immunoglobulinDrug
Also called IVIG, Intratect
This is a blood product containing antibodies from thousands of healthy donors.
PlaceboDrug
Also called Saline solution
This is the control, or sham, treatment
RituximabDrug
Also called MabThera
Rituximab is a type of biological therapy. It removes B-cells and helps to reduce the inflammation
| Study group | Role | What they receive |
|---|---|---|
| Intravenous immunoglobulin and Rituximab | Active comparator | One cycle of intravenous immunoglobulin (IVIG) 2g/kg over 2-5 days (days 1-5) followed by (b) two infusions of 1g rituximab (the first infusion starting between days 28-35, and the second infusion 14 days later), each with 100mg methylprednisolone. Receives: Drug: Intravenous immunoglobulin; Drug: Rituximab |
| Placebo | Placebo comparator | One cycle of 0.9% saline solution over 2-5 days (days 1-5) followed by (b) two infusions of placebo solution alongside placebo pill - in equal volumes to steroid pre-medication and rituximab. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to start of symptomatic recovery (symptomatic remission sustained for at least 6 months)
remission defined as Positive and Negative Syndrome Scale (PANSS) score 3 or less on PANSS items P1, P2, P3, N1, N4, N6, G5 and G9 sustained for 6 months
Measured: up to 18 months
Secondary outcomes (11)
Time to first treatment response (whether sustained or not)
Treatment response defined as score of 3 or less on each of the following PANSS items: P1, P2, P3, N1, N4, N6, G5, and G9.
Measured: up to 18 months
Relapse rate
Relapse rate is defined as a score 4 or more on PANSS items P1, P2, P3, N1, N4, N6, G5, and G9.
Measured: 18 months
Number of adverse effects
total number of patient reported adverse effects
Measured: 18 months
Proportion of patients reaching 20% reduction in PANSS total score
20% reduction in the PANSS total score (all PANNS items included)
Measured: 12 months
Proportion of patients reaching 30% reduction in PANSS total score
30% reduction in the PANSS total score (all PANNS items included)
Measured: 12 months
Proportion of patients reaching 40% reduction in PANSS total score
40% reduction in the PANSS total score (all PANNS items included)
Measured: 12 months
Changes in the Clinical Global Impression Scale in Schizophrenia (CGI-Schizophrenia)
Change in CGI-Schizophrenia scores from baseline to month 12
Measured: 12 months
Changes in the Young Mania Rating Scale (YMRS)
Change in YMRS total score from baseline to month 12
Measured: 12 months
Changes in the Antipsychotic Non-Neurological Side-Effects Rating Scale (ANNSERS)
Change in ANNSERS total score from baseline to month 12
Measured: 12 months
Changes in the Brief Assessment of Cognition in Schizophrenia (BACS)
Change in BACS scores from baseline to month 12
Measured: 12 months
Changes in the Global Assessment of Functioning scale (GAF)
Change in the GAF score from baseline to month 12
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2017
- Study start1 Nov 2017
- Primary completion30 Apr 2027 (estimated)
- Study completion30 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PsychosisStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Cambridge
- Sponsor type
- University, hospital or other
- Collaborators
- University of Oxford
- Responsible party
- Principal investigator, Alasdair Coles, University of Cambridge
- Investigators
- Alasdair Coles, PhD FRCP, Principal investigator, University of Cambridge, UK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03194815
- Sponsor's protocol ID
- SINAPPS 2
- Acronym
- SINAPPS2
- Status last verified
- May 2026
- First submitted
- 2 Feb 2017
- Last updated
- 22 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Lennox B, Yeeles K, Jones PB, Zandi M, Joyce E, Yu LM, Tomei G, Pollard R, Vincent SA, Shimazaki M, Cairns I, Dowling F, Kabir T, Barnes TRE, Lingford Hughes A, Hosseini AA, Harrower T, Buckley C, Coles A. Intravenous immunoglobulin and rituximab versus placebo treatment of antibody-associated psychosis: study protocol of a randomised phase IIa double-blinded placebo-controlled trial (SINAPPS2). Trials. 2019 Jun 7;20(1):331. doi: 10.1186/s13063-019-3336-1.
PubMed 31174586
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Phase II Double-blinded Placebo-controlled Trial of Intravenous Immunoglobulins and Rituximab in Patients With Antibody-associated Psychosis (SINAPPS2)
- ClinicalTrials.gov ID
- NCT03194815
- Acronym / sponsor ID
- SINAPPS2 / SINAPPS 2
- Conditions
- Psychosis, Autoimmune Encephalitis
- Keywords
- Psychosis, Immunotherapy, Autoantibodies
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- University of CambridgeUniversity, hospital or other
- Collaborators
- University of Oxford
- Study start
- 1 Nov 2017 (actual)
- Primary completion
- 30 Apr 2027 (estimated)
- Study completion
- 30 Apr 2027 (estimated)
- First posted
- 21 Jun 2017 (actual)
- 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.
A randomised phase II double-blinded placebo-controlled trial designed to explore the utility of immunotherapy for patients with acute psychosis associated with anti-neuronal membranes (NMDA-receptor or Voltage Gated Potassium Channel).
Primary objective: To test the efficacy of immunotherapy (IVIG and rituximab) for patients with acute psychosis associated with anti-neuronal membranes.
Secondary objective: To test safety of immunotherapy (IVIG and rituximab) for patients with acute psychosis associated with anti-neuronal membranes.
Detailed description
Investigators propose a randomised double-blinded placebo-controlled trial to test the hypothesis that immunotherapy is an effective treatment of antibody-associated psychosis, either first episode of psychosis or relapse following previous remission. Immunotherapy for the trial consists of one cycle of intravenous immunoglobulin (IVIG: 2g/kg over days 1-4) followed by two infusions of 1g rituximab (at day 28-35, and then 14 days after the first infusion). The rationale for this regime is that it combines a rapid-action treatment (IVIG) to induce remission with a longer-action therapy (rituximab) to maintain remission. It is based on a protocol where elimination of circulating antibodies is the treatment goal, namely "desensitisation" of potential transplant patients who have multiple anti-HLA antibodies capable of inducing hyperacute rejection and also being tested in various trials on clinicaltrials.gov (NCT00642655, NCT01178216, and NCT01502267). Blinding is required to minimise placebo responses in a trial based on symptomatology.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intravenous immunoglobulin and Rituximab | Active comparator | Drug: Intravenous immunoglobulin, Drug: RituximabOne cycle of intravenous immunoglobulin (IVIG) 2g/kg over 2-5 days (days 1-5) followed by (b) two infusions of 1g rituximab (the first infusion starting between days 28-35, and the second infusion 14 days later), each with 100mg methylprednisolone. |
| Placebo | Placebo comparator | Drug: PlaceboOne cycle of 0.9% saline solution over 2-5 days (days 1-5) followed by (b) two infusions of placebo solution alongside placebo pill - in equal volumes to steroid pre-medication and rituximab. |
Who may qualify
- Ages
- 16 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Acute psychosis >2 weeks. This may either be first episode or relapse after remission (remission defined as having mild or absent symptoms of psychosis for at least 6 months)
- Serum or CSF neuronal membrane autoantibodies at pathological levels (including NMDAR, LGI1 and other)
- Psychosis symptoms as defined by PANSS ≥4 on at least one of the following items: P1, P2, P3, N1, N4, N6, G5 and G9.
Key exclusion criteria (6 listed)
- Current episode of psychosis greater than 24 months duration
- Co-existing severe neurological disease
- Evidence of current acute encephalopathy
- Hepatitis or HIV infection, pregnancy
- Contraindications to any trial drug
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 |
|---|---|---|
| Intravenous immunoglobulinAlso: IVIG, IntratectThis is a blood product containing antibodies from thousands of healthy donors. | Drug | Intravenous immunoglobulin and Rituximab |
| PlaceboAlso: Saline solutionThis is the control, or sham, treatment | Drug | Placebo |
| RituximabAlso: MabTheraRituximab is a type of biological therapy. It removes B-cells and helps to reduce the inflammation | Drug | Intravenous immunoglobulin and Rituximab |
Primary outcome
Time to start of symptomatic recovery (symptomatic remission sustained for at least 6 months)
Time frame: up to 18 months
remission defined as Positive and Negative Syndrome Scale (PANSS) score 3 or less on PANSS items P1, P2, P3, N1, N4, N6, G5 and G9 sustained for 6 months
11 secondary outcomes
Time to first treatment response (whether sustained or not)
Time frame: up to 18 months
Relapse rate
Time frame: 18 months
Number of adverse effects
Time frame: 18 months
Proportion of patients reaching 20% reduction in PANSS total score
Time frame: 12 months
Proportion of patients reaching 30% reduction in PANSS total score
Time frame: 12 months
Proportion of patients reaching 40% reduction in PANSS total score
Time frame: 12 months
Changes in the Clinical Global Impression Scale in Schizophrenia (CGI-Schizophrenia)
Time frame: 12 months
Changes in the Young Mania Rating Scale (YMRS)
Time frame: 12 months
Changes in the Antipsychotic Non-Neurological Side-Effects Rating Scale (ANNSERS)
Time frame: 12 months
Changes in the Brief Assessment of Cognition in Schizophrenia (BACS)
Time frame: 12 months
Changes in the Global Assessment of Functioning scale (GAF)
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2026.
- Derived from this study: PubMed 31174586Lennox B, Yeeles K, Jones PB, Zandi M, Joyce E, Yu LM, Tomei G, Pollard R, Vincent SA, Shimazaki M, Cairns I, Dowling F, Kabir T, Barnes TRE, Lingford Hughes A, Hosseini AA, Harrower T, Buckley C, Coles A. Intravenous immunoglobulin and rituximab versus placebo treatment of antibody-associated psychosis: study protocol of a randomised phase IIa double-blinded placebo-controlled trial (SINAPPS2). Trials. 2019 Jun 7;20(1):331. doi: 10.1186/s13063-019-3336-1.
- SINAPPS Group websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
Related trials for Psychosis
RecruitingPhase 3
A Study to Evaluate the Long-term Safety and Tolerability of Xanomeline and Trospium Chloride for the Treatment of Psychiatric Disorders in Children and Adolescents
Schizophrenia, Autism-Related Irritability
Not yet recruitingObservational study
Sleep Monitoring for Early Detection of Relapse in People With Schizophrenia or Bipolar Disorder Receiving Usual Treatment
Bipolar Disorder (BD), SCHIZOPHRENIA 1 (Disorder)
Not yet recruitingPhase 1
Pharmacokinetics and Relative Bioavailability of Intranasal vs Intramuscular Olanzapine in Healthy Adult Participants
Healthy Adult Participants
Active, not recruiting
Designing and Evaluating a Classroom-Based Mental Health Programme for Adolescents.
Mental Health Promotion
RecruitingPhase 2/3
ACP-204 in Adults With Alzheimer's Disease Psychosis
Alzheimer's Disease Psychosis
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, PhD FRCP principal investigator
University of Cambridge, UK
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Intravenous immunoglobulin and Rituximab in people with Psychosis and Autoimmune Encephalitis, run by University of Cambridge at 10 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 6 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: under way, not looking for participants, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Time to start of symptomatic recovery (symptomatic remission sustained for at least 6 months) (time frame: up to 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03194815, which also lists 1 linked publication.
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 22 May 2026.