Fluoxetine : Clinical and Anatomy-functional Therapeutic Effects in Children With Autism
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Subscores of Autism Diagnostic Interview (ADI-R)at each visit of the protocol (LECOUTER et RUTTER, 1989)
研究概览
简要总结
This study is a comparative, double blind, placebo controlled trial of 6-months duration designed to evaluate 1) the effects of fluoxetine in 5 to 12 years old autistic children, 2) the effects of fluoxetine on serotoninergic parameters, 3) cerebral metabolic changes (rCBF measurements with PET) induced by the treatment.
详细描述
Autism is a severe neurodevelopmental disorder characterized by impaired social interaction and communication, and by a markedly restricted repertoire of activities and interests. The population prevalence of autism is approximately 1 in 1000 (GILLBERG and WING, 1999) and the ratio of affected males to females is 4:1 (FOMBONNE, 1999). Although typically considered a childhood disorder, most persons with autism experience marked functional impairment throughout their lives. Follow-up studies of children with autism show that only 5%-10% become independent as adults, 25% progress but still require supervision, and the remaining continue to be severely impaired and in need of institutionalized care (WING, 1989). Thus, the syndrome represents a substantial public health problem with tragic cost to the individual, the family, and the community.
It is a randomized, double blind flexible dose study with parallel groups, controlled, fluoxetine versus placebo.
The final efficacy evaluation will be done after 6 months of treatment; Nine obligatory visits are planned Patients will be assessed at the following visits: base-line inclusion (D-15), and 2, 4, ,12, ,20, 22, 24 25, 26 weeks. At the 24 W visit, the final efficacy will be performed and medication will be tapered over a maximum period of 2 weeks. The final safety assessment will be performed at 26W.
BRAIN IMAGING PROTOCOL :
We will assess the resting state regional cerebral blood flow (rCBF) in autistic children using labeled water and PET, as it is still the most reliable and least invasive method. In addition, an anatomical and functional MRI will be performed in all children, the same day. Brain imaging studies will be performed at the Service HOSPITALIER Frederic JOLIOT (ORSAY, France) under Dr Monica ZILBOVICIUS responsibility.
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
- 5 Years 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female subjects with diagnosis of Pervasive developmental disorder (PDD) meeting all criteria listed bellow will be included in the study:
- •age 5 to 12 years, outpatients.
- •presenting with a primary diagnosis of autism according to DSM- IV-R.
- •Autism will be diagnosed with Autism Diagnostic Interview (ADI)
- •with a score of 30 or above on the Children Autistic Rating Scale (CARS, SCHOPLER et al., 1980).
- •Written informed consent obtained from each patient's parents or legal guardian.
排除标准
- •Subjects presenting with any of the following will not be included in the study:
- •Participation in any other studies involving investigational or marketed products within 6 months prior to entry in the study.
- •Treatment given for autism within the previous 1 month
- •Organic mental disorder or organic brain syndrome (including epilepsy)
- •Severe mental retardation (IQ < 45).
- •Specific systemic diseases, including history of significant hematological, endocrine, cardiovascular, renal, gastrointestinal or neurological disease (including more than one episode of childhood febrile convulsion).
- •Medical contra-indication to treatment with any antidepressant and specially sertraline
- •Previous history of intolerance or hypersensitivity to fluoxetine or to drugs with similar chemical structures
- •Currant use of concomitant anticoagulant therapy
- •Previous participation in any other clinical trial with the study drug
- •Require concomitant therapy with any psychotropic drug or with any drug with a psychotropic component
研究组 & 干预措施
Fluoxetine arm
Treatment with fluoxetine in an oral solution will be given at 0.25mg/kg day during 2 weeks and at 0.4mg/kg day during 16 weeks.
A progressive decreased of dosage on a period of 4 weeks to 0.25mg/kg/day (2 weeks) and 0.10mg/kg/day(2 weeks) will be realized
干预措施: fluoxetine (Drug)
placebo arm
Placebo comparator. The packaging of study drug and placebo will be performed according to applicable regulatory requirements in the same packaging. An oral solution will be administrated.
干预措施: placebo (Drug)
结局指标
主要结局
Subscores of Autism Diagnostic Interview (ADI-R)at each visit of the protocol (LECOUTER et RUTTER, 1989)
时间窗: 6 months
次要结局
- Sides effect scale (FSEC)(6 months)
- Aberrant Behavior Checklist (Aman et al., 1985)(6 months)
- Clinical Global Impressions (CGI) severity and improvement (NIMH.1985)(6 months)