Melatonin Dose-effect Relation in Childhood Autism
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 34
- 试验地点
- 4
- 主要终点
- Severity of autistic disorder
研究概览
简要总结
Melatonin is a neurohormone produced from serotonin which promotes sleep. The alterations in central and peripheral serotonin neurobiology and in circadian sleep-wake rhythms observed in autistic disorder suggest abnormalities in melatonin secretion.
Several studies have reported a decrease in melatonin secretion in individuals with autism. Furthermore, nocturnal excretion of 6-Sulphatoxymelatonin (the predominant melatonin metabolite) was significantly negatively correlated with severity of autistic impairments in verbal communication and play. Melatonin could therefore have a therapeutic effect on sleep problems and may play a role in the pathophysiology of autistic disorder.
These data highlight the possible therapeutic interest of an oral administration of melatonin in patients with autistic disorder. Thus, the objective of this clinical trial is to study the relation between the melatonin dose administered and its effect on severity of autistic impairments especially in verbal communication and play.
详细描述
The hormone melatonin is of interest in autism due to theoretical considerations and reports of altered melatonin production in individuals with autism. Melatonin produced in the pineal gland helps regulate human circadian rhythms including sleep-wake, and is considered as the best measure of circadian rhythms.
Several studies revealed that plasmatic and urinary nocturnal levels of melatonin are significantly lower in individuals with autism (in particular, in prepubertal children) compared to typically developing individuals. In addition, this reduction in nocturnal melatonin was significantly associated with the severity of communication and social interaction impairments, especially in verbal communication and play. Finally, diurnal excretion of melatonin was also found to be decreased in individuals with autistic disorder.
Given these results, administration of melatonin could serve, at least in prepubertal children wih autism, to normalize physiological, developmental and behavioral processes that are influenced by this pineal hormone. A randomized clinical trial is therefore necessary to establish potential therapeutic efficacy of melatonin in autistic disorder and to specify its dose-effect relation. This is the first clinical trial studying the melatonin dose-effect in 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
- 6 Years 至 8 Years（Child）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Prepubertal males with autism from 6 to 8 years old, according to the diagnostic criteria of autistic disorder of the WHO (CIM-10), American (DSM-IV-TR) and French (CFTMEA) classifications.
- •Verbal language level required for the ADOS (Module 1) (i.e., no verbal language as defined by the ADI-R (autism diagnostic interview-revised) scale).
- •Written informed consent of the parents or the legal representative.
- •Non-inclusion Criteria:
- •Treatment by benzodiazepines.
- •Treatment by anticonvulsant drugs.
- •Treatment by serotoninergic products.
- •Hypersensitivity reaction to the active substance or one of the excipients of the product.
- •Patient with hereditary galactose intolerance, Lapp lactase deficiency or malabsorption syndrome of glucose and galactose.
- •Children who are not able to swallow tablets.
排除标准
- 未提供
研究组 & 干预措施
Placebo
5 tablets of placebo once a day, an hour before falling asleep, for 6 weeks.
干预措施: Placebo (Drug)
2 mg melatonin
1 tablet of 2mg melatonin and 4 tablets of its placebo once a day, an hour before falling asleep, for 6 weeks.
干预措施: melatonin (Drug)
2 mg melatonin
1 tablet of 2mg melatonin and 4 tablets of its placebo once a day, an hour before falling asleep, for 6 weeks.
干预措施: Placebo (Drug)
4 mg melatonin
2 tablets of 2mg melatonin and 3 tablets of its placebo once a day, an hour before falling asleep, for 6 weeks.
干预措施: melatonin (Drug)
4 mg melatonin
2 tablets of 2mg melatonin and 3 tablets of its placebo once a day, an hour before falling asleep, for 6 weeks.
干预措施: Placebo (Drug)
10 mg melatonin
5 tablets of 2mg melatonin once a day, an hour before falling asleep, for 6 weeks.
干预措施: melatonin (Drug)
结局指标
主要结局
Severity of autistic disorder
时间窗: 6 weeks after the beginning of the treatment.
次要结局
- Severity of autistic impairments(6 weeks after the beginning of the treatment)
- Excretion of the urinary metabolite of melatonin(6 weeks after the beginning of the treatment)
- Sleep problems(6 weeks after the beginning of the treatment)