Antibiotic Treatment and Intravenous Immunoglobulin Double-blind, Randomized, Placebo-controlled Trial for PANDAS
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- 主要终点
- The improvement of OC/tic symptoms will be superior in patients treated with SSRI+AB and in case with IVIG, compared with those treated with SSRI+placebo, as assessed by the YBOCS/YGTSS
研究概览
简要总结
An increasing body of evidence indicates that an immune basis might underline a number of pediatric neuropsychiatric disorders. Research studies found a subgroup of children who had Obsessive compulsive (OCD) and/or tic disorders following a Group A beta-hemolytic streptococcal (GAS) infection. The subgroup is identified by the acronym, PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. More recently, several PANDAS variants have been described, including adult-onset variant. There are many evidences that OCD/tic symptoms could be due to an immunologic reaction against brain tissues following a streptococcal infection.
The purpose of this study is to know if sertraline (one of the SSRI approved by FDA to improve OCD/tic symptoms in these patients) plus antibiotic (benzathine penicillin G or azithromycin in case of penicillin allergy) is more effective than SSRI only.
Patients who will not respond to antibiotic will be treated with intravenous immunoglobulin (IVIG) in order to inactivate the immune reaction versus brain tissues.(No treatment response is based on the lack of a Y-BOCS score improvement of at least 35%).
Objectives:
- To determine the safety and efficacy of SSRI+AB compared to SSRI only.
- To test the safety and additional beneficial effects of high dose of IVIG on antibiotic prophylaxis for the treatment of OCD symptoms in non-responders patients with PANDAS.
Study methodology:
- Participants will be screened to obtain medical history and other information at Neurologic and Psychiatric Sciences Department of Florence University Hospital and at Paris-est University.
- Participants will receive a treatment of either SSRI+AB or SSRI+placebo for 12 weeks (double-blind randomized trial)
- Patients who will not respond to AB will be admitted to the hospital to receive IVIG for 5 days, for 5 consecutive months.
- Follow-up visits will take place 3 and 6 months after the first evaluation, followed by 6 months follow-ups for 3 additional years.
Blood samples (including blood cytokine determination), ECG, Doppler and 2-dimensional echocardiogram EEG, imaging studies (2 tesla MRI), and other tests will be performed both before and after the treatment with SSRI+AB or SSRI+placebo and in case also after IVIG treatment.
详细描述
Inclusion criteria for PANDAS subjects are:
- Ages 4 -40 years
- Presence of DSM-IV-R obsessive compulsive disorder or tic disorder and at least two of the following:
- Anxieties e.g. new onset separation anxiety
- Sensory abnormalities (tactile/auditory/visual defensiveness or visual misperceptions)
- Behavioral Regression (e.g. new onset impulsivity, hyperactivity, meltdowns)
- Deterioration in school performance or in handwriting
- Emotional lability and/or depression
- Urinary symptoms (frequent urination or enuresis)
- Sleep disturbances
- Anorexia
- Sudden onset of symptoms or episodic course of symptom severity following infections.
- Symptoms are of moderate severity with Yale-Brown Obsessive Compulsive Scale (Y-BOCS) (or with the children's version for subjects below 16 years of age) of more or equal to 16 and/or Yale Global Tic Severity Scale (YGTSS) of more or equal to 21 and with significant impairment (CGI of moderate or worse).
- Laboratory documentation of infection as documented by at least two of these: positive throat culture, documented rise in one or more anti-GAS antibody titers such as anti-streptolysin O, anti-streptococcal DNAaseB.
Exclusion criteria for all subjects are: non-tic neurologic disorder, presence of immunologic disorder, presence of serious medical illness, IgA deficiency (< 20mg/dL), hyperviscosity syndromes, psychotropic therapy.
Interventions:
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
- 4 Years 至 40 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ages 4 -40 years
- •Presence of DSM-IV-R obsessive compulsive disorder or tic disorder and at least two of the following:
- •Anxieties e.g. new onset separation anxiety
- •Sensory abnormalities (tactile/auditory/visual defensiveness or visual misperceptions)
- •Behavioral Regression (e.g. new onset impulsivity, hyperactivity, meltdowns)
- •Deterioration in school performance or in handwriting
- •Emotional lability and/or depression
- •Urinary symptoms (frequent urination or enuresis)
- •Sleep disturbances
- •Sudden onset of symptoms or episodic course of symptom severity following infections
- •Laboratory documentation of infection
排除标准
- •Exclusion criteria for all subjects are: non-tic neurologic disorder, presence of immunologic disorder, presence of serious medical illness, IgA deficiency (< 20mg/dL), hyperviscosity syndromes, psychotropic therapy.
研究组 & 干预措施
SSRI+AB
Intervention: sertraline+antibiotic (penicillin/azithromycin) 12 weeks treatment with a combination of sertraline (to a maximum of 200 mg/day)and one antibiotic ( benzathine penicillin G 1.200.000 U every 3 weeks or, in case of allergy, azithromycin 500 mg/week ). Patients who will not respond to SSRI+antibiotic (penicillin/azithromycin) will be treated with IVIG (2g/kg over 5 days for 5 consecutive months)
干预措施: Sertraline+Antibiotic (penicillin/azithromycin) (Drug)
SSRI+AB
Intervention: sertraline+antibiotic (penicillin/azithromycin) 12 weeks treatment with a combination of sertraline (to a maximum of 200 mg/day)and one antibiotic ( benzathine penicillin G 1.200.000 U every 3 weeks or, in case of allergy, azithromycin 500 mg/week ). Patients who will not respond to SSRI+antibiotic (penicillin/azithromycin) will be treated with IVIG (2g/kg over 5 days for 5 consecutive months)
干预措施: IVIG (Biological)
SSRI+placebo
Intervention: Sertraline+placebo 12 weeks treatment with a combination of sertraline (to a maximum of 200 mg/day) and a placebo
干预措施: Sertraline+placebo (Drug)
结局指标
主要结局
The improvement of OC/tic symptoms will be superior in patients treated with SSRI+AB and in case with IVIG, compared with those treated with SSRI+placebo, as assessed by the YBOCS/YGTSS
时间窗: 6 months
次要结局
- The degree of treatment response is also expected to correlate with decreased inflammation in specific regions of the brain, as demonstrated by macroscopic changes and microstructural alterations on MRI and serum and CSF cytokines and chemokines(6 months)
- The degree of treatment response is expected to correlate with the percentage reduction in antibodies titers following IVIG administration(6 months)
研究者
Stefano Pallanti
Associate Professor
CNS Onlus