A Randomised Phase II Double-blinded Placebo-controlled Trial of Intravenous Immunoglobulins and Rituximab in Patients With Antibody-associated Psychosis (SINAPPS2)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 70
- 试验地点
- 20
- 主要终点
- Time to start of symptomatic recovery (symptomatic remission sustained for at least 6 months)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 16 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Placebo
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.
干预措施: Placebo (Drug)
Intravenous immunoglobulin and Rituximab
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.
干预措施: Intravenous immunoglobulin (Drug)
Intravenous immunoglobulin and Rituximab
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.
干预措施: Rituximab (Drug)
结局指标
主要结局
Time to start of symptomatic recovery (symptomatic remission sustained for at least 6 months)
时间窗: 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
次要结局
- Changes in the Clinical Global Impression Scale in Schizophrenia (CGI-Schizophrenia)(12 months)
- Time to first treatment response (whether sustained or not)(up to 18 months)
- Number of adverse effects(18 months)
- Changes in the Brief Assessment of Cognition in Schizophrenia (BACS)(12 months)
- Changes in the Global Assessment of Functioning scale (GAF)(12 months)
- Relapse rate(18 months)
- Proportion of patients reaching 20% reduction in PANSS total score(12 months)
- Proportion of patients reaching 30% reduction in PANSS total score(12 months)
- Changes in the Antipsychotic Non-Neurological Side-Effects Rating Scale (ANNSERS)(12 months)
- Proportion of patients reaching 40% reduction in PANSS total score(12 months)
- Changes in the Young Mania Rating Scale (YMRS)(12 months)
研究者
Alasdair Coles
Revd. Prof. Alasdair Coles, Chief Investigator
University of Cambridge