Novel Pharmacological Strategies in Autism
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 81
- 试验地点
- 1
- 主要终点
- Mean Post-baseline Aberrant Behavior Checklist Irritability Score, Parent Report, Double-blind Phase
研究概览
简要总结
This study will determine the effectiveness of aripiprazole and D-Cycloserine in treating symptoms associated with autism in children.
详细描述
Autism is a developmental disorder that affects every child differently. A wide range of symptoms accompany autism, including self-injurious behavior, aggression, and severe tantrums. Despite an improved ability to reduce these symptoms, existing drug treatments continue to be associated with adverse side effects. Also, there is no existing drug treatment that reliably improves social behavior, a core deficit in autism. Studies on drug treatment combinations that are designed to reduce self-injurious behavior, aggression, and severe tantrums and improve social behavior in children with autism have yet to be conducted. This study will address the above-mentioned limitations by evaluating aripiprazole in reducing self-injurious behavior, aggression, and severe tantrums and by evaluating the addition of D-Cycloserine in improving social behavior among children with autism.
This study will include three phases and an add-on component for some children. Participants will be randomly assigned to receive either aripiprazole or a placebo treatment for 8 weeks. Assessments measuring irritability, behavior, and social skills will be conducted at the end of this first phase. Those patients who respond well to aripiprazole will continue to receive aripiprazole treatment for another 16 weeks. This second phase will determine whether aripiprazole is associated with long-term maintenance of symptomatic improvement in patients who respond well to short-term treatment. Assessments will again be conducted at the end of this 16-week period. Those patients whose symptoms have stabilized and continue to improve while on aripiprazole will be asked to participate in the final phase of this study. During the this pilot phase, D-Cycloserine will be added to ongoing treatment with aripiprazole. Patients will take both aripiprazole and D-Cycloserine for an additional 8 weeks to determine if this combination of drug treatments results in improved social behavior once patients' aggression and self-injurious behavior have been stabilized with aripiprazole. At the end of this 8-week period, participants will be assessed for any changes in behavior, irritability, or social skills. Results from this study may aid in developing safer and more effective drug treatments for children and adolescents with autism.
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 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Weight of at least 15 kg (33.75 lbs)
- •Meets DSM-IV criteria for autistic disorder
- •Outpatient
- •Medication-free for at least 2 weeks prior to baseline for all psychotropic medications. More information about this criterion, including exceptions, can be found in the protocol.
- •Clinical Global Impression Scale Severity score (CGI-S) of at least 4
- •Irritability subscale of the Aberrant Behavior Checklist (ABC) score of at least 18
- •An IQ of at least 35 or a mental age of at least 18 months
- •In good physical health
排除标准
- •Meets DSM-IV criteria for Asperger's disorder, Rett's disorder, childhood disintegrative disorder, any other pervasive developmental disorder (PDD), schizophrenia, psychotic disorder, or bipolar disorder
- •Current or past history of alcohol or other substance abuse within 6 months of study entry
- •Comorbid neurodevelopmental disorder with possible association to autism (e.g., fragile-X syndrome, tuberous sclerosis)
- •A significant medical condition such as heart, liver, kidney, or lung disease, or a seizure disorder
- •Prior adequate use of aripiprazole. More information about this criterion can be found in the protocol.
- •Evidence of hypersensitivity to aripiprazole
- •History of neuroleptic malignant syndrome
研究组 & 干预措施
1 Placebo
Participants will take placebo
干预措施: Placebo (Drug)
2 Aripiprazole
Participants will take aripiprazole
干预措施: Aripiprazole (Drug)
3 Aripiprazole + D-cycloserine
Participants first will take aripiprazole then will also take D-cycloserine
干预措施: Aripiprazole (Drug)
3 Aripiprazole + D-cycloserine
Participants first will take aripiprazole then will also take D-cycloserine
干预措施: D-cycloserine (Drug)
结局指标
主要结局
Mean Post-baseline Aberrant Behavior Checklist Irritability Score, Parent Report, Double-blind Phase
时间窗: Weeks 1, 2, 3, 4, 6, and 8
The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its subscales is that higher scores, indicate greater severity. Fifteen item scores with values ranging from 0 (not a problem) to 3 (problem is severe) are summed to arrive at the total irritability scale store ranging from 0 to 45. Means were estimated using a repeated measures linear regression model with treatment group, baseline score, study week (in categories), and sex x Tanner stage stratum as covariates. A linear contrast estimated the average across study timepoints. Confidence intervals reflect a Bonferroni multiple testing correction accounting
Odds of Improvement as Measured by the Clinical Global Impression-Global Improvement Scale (Improvement Defined as CGI-I=1 or CGI-I=2)
时间窗: Weeks 1, 2, 3, 4, 6 and 8
Clinical Global Impressions (Guy, 1976) global improvement (CGI-I) is designed to take into account all factors to arrive at an assessment of response to treatment. The CGI-I scale ranges from 1 to 7, with lower scores indicating greater improvement (1=very much improved and 2=much improved). Participants with a CGI-I score of 1 or 2 were classified as improved. Odds were estimated using a repeated measures logistic regression model with treatment group, study week (in categories), and sex x Tanner stage stratum as covariates. A linear contrast estimated the average log odds across study timepoints. Confidence intervals reflect a Bonferroni multiple testing correction accounting for the selection of two primary outcomes.
次要结局
- Mean Post-baseline Aberrant Behavior Checklist Inappropriate Speech Score, Parent Report, Double-blind Phase(Weeks 1, 2, 3, 4, 6, and 8)
- Mean Post-baseline Score on a Modified Version of the Compulsion Subscale of the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS)(Weeks 2, 4, 6 and 8)
- Mean Post-baseline Aberrant Behavior Checklist Social Withdrawal Score, Parent Report, Double-blind Phase(Weeks 1, 2, 3, 4, 6, and 8)
- Mean Post-baseline Aberrant Behavior Checklist Stereotypy Score, Parent Report, Double-blind Phase(Weeks 1, 2, 3, 4, 6, and 8)
- Mean Autism Diagnostic Observation Schedule (ADOS) Social Affect and Restricted and Repetitive Behaviors Total Score, Week 8(Week 8)
- Mean Post-baseline Aberrant Behavior Checklist Hyperactivity Score, Parent Report, Double-blind Phase(Weeks 1, 2, 3, 4, 6 and 8)
- Mean Vineland Maladaptive Behavior Subscales Total Score, Week 8(Week 8)
- Mean Social Reciprocity Scale (SRS) Total Score, Week 8(Week 8)