Dataset Information

Sleep, Growth, and Puberty After 2 Years of Prolonged-Release Melatonin in Children With Autism Spectrum Disorder.

ABSTRACT:

Objective

A recent 3-month double-blind, placebo-controlled study demonstrated efficacy and safety of pediatric prolonged-release melatonin (PedPRM) for insomnia in children with autism spectrum disorder. This study examined the long-term effects of PedPRM treatment on sleep, growth, body mass index, and pubertal development.

Method

Eighty children and adolescents (2-17.5 years of age; 96% with autism spectrum disorder) who completed the double-blind, placebo-controlled trial were given 2 mg, 5 mg, or 10 mg PedPRM nightly up to 104 weeks, followed by a 2-week placebo period to assess withdrawal effects.

Results

Improvements in child sleep disturbance and caregiver satisfaction with child sleep patterns, quality of sleep, and quality of life were maintained throughout the 104-week treatment period (p < .001 versus baseline for all). During the 2-week withdrawal placebo period, measures declined compared with the treatment period but were still improved compared with baseline. PedPRM was generally safe; the most frequent treatment-related adverse events were fatigue (6.3%), somnolence (6.3%), and mood swings (4.2%). Changes in mean weight, height, body mass index, and pubertal status (Tanner staging done by a physician) were within normal ranges for age with no evidence of delay in body mass index or pubertal development.

Conclusion

Nightly PedPRM at optimal dose (2, 5, or 10 mg nightly) is safe and effective for long-term treatment in children and adolescents with autism spectrum disorder and insomnia. There were no observed detrimental effects on children's growth and pubertal development and no withdrawal or safety issues related to the use or discontinuation of the drug.

Clinical trial registration information

Efficacy and Safety of Circadin in the Treatment of Sleep Disturbances in Children With Neurodevelopment Disabilities; https://clinicaltrials.gov/; NCT01906866.

SUBMITTER: Malow BA

PROVIDER: S-EPMC8084705 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Objective: A recent double-blind randomized placebo-controlled study demonstrated 3-month efficacy and safety of a novel pediatric-appropriate prolonged-release melatonin (PedPRM) for insomnia in children and adolescents with autism spectrum disorder (ASD) and neurogenetic disorders (NGD) with/without attention-deficit/hyperactivity disorder comorbidity. Long-term efficacy and safety of PedPRM treatment was studied. Methods: A prospective, open-label efficacy and safety follow-up of nightly 2, 5, or 10?mg PedPRM in subjects who completed the 13-week double-blind trial (51 PedPRM; 44 placebo). Measures included caregiver-reported Sleep and Nap Diary, Composite Sleep Disturbance Index (CSDI), caregiver's Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale, and quality of life (WHO-5 Well-Being Index). Results: Ninety-five subjects (74.7% males; mean [standard deviation] age, 9 [4.24]; range, 2-17.5 years) received PedPRM (2/5?mg) according to the double-blind phase dose, for 39 weeks with optional dose adjustment (2, 5, or 10?mg/day) after the first 13 weeks. After 52 weeks of continuous treatment (PedPRM-randomized group) subjects slept (mean [SE]) 62.08 (21.5) minutes longer (p?=?0.007); fell asleep 48.6 (10.2) minutes faster (p?<?0.001); had 89.1 (25.5) minutes longer uninterrupted sleep episodes (p?=?0.001); 0.41 (0.12) less nightly awakenings (>50% decrease; p?=?0.001); and better sleep quality (p?<?0.001) compared with baseline. The placebo-randomized group also improved with PedPRM. Altogether, by the end of 39-week follow-up, regardless of randomization assignment, 55/72 (76%) of completers achieved overall improvement of ?1 hour in total sleep time (TST), sleep latency or both, over baseline, with no evidence of decreased efficacy. In parallel, CSDI child sleep disturbance and caregivers' satisfaction of their child's sleep patterns (p?<?0.001 for both), PSQI global (p?<?0.001), and WHO-5 (p?=?0.001) improved in statistically significant and clinically relevant manner (n?=?72) compared with baseline. PedPRM was generally safe; most frequent treatment-related adverse events were fatigue (5.3%) and mood swings (3.2% of patients). Conclusion: PedPRM, an easily swallowed formulation shown to be efficacious versus placebo, is an efficacious and safe option for long-term treatment (up to 52 weeks reported here) of children with ASD and NGD who suffer from insomnia and subsequently improves caregivers' quality of life.

Project description:BackgroundHigh prevalence of sleep problems have been reported in children with Autism Spectrum Disorder (ASD). This study aims to investigate the sleep conditions of ASD children in China, and explore the relationship between the common sleep problems and core symptoms and developmental levels.MethodsUsing a cross-sectional design, we included 2 to 7-year-old children from 13 cities in China: 1310 with ASD and 1158 with typically-developing (TD) children. The neurodevelopmental level was evaluated with the revised Children Neuropsychological and Behavior Scale (CNBS-R2016). ASD were diagnosed with DSM-5 and Child Autism Rating Scale (CARS). the Social Responsiveness Scale (SRS), the Autism Behavior Checklist (ABC) and the communication warning behavior sub-scale in CNBS-R2016 valued autism behaviors. The children' s sleep habits questionnaire (CSHQ) assessed sleep conditions.ResultsThe prevalence of sleep disorders in ASD children was significantly higher than that in TD (67.4% vs. 51%, p < 0.01), and among them the four dimensions with the highest prevalence of sleep problems were bedtime resistance (25.6%), sleep anxiety (22.7%), sleep onset delay (17.9%) and daytime sleepiness (14.7%). ASD children with sleep onset delay or sleep anxiety had higher ABC, SRS scores and higher scores on communication warning behavior with sleep anxiety, with daytime sleepiness had higher ABC, SRS and CARS scores, and with bedtime resistance had higher SRS total scores. Differences in the neurodevelopmental level were not significant.ConclusionChildren with ASD have a higher prevalence of sleep problems. Bedtime resistance, anxiety, sleep onset delay and daytime sleepiness may be related to the core symptoms, but not be related to the developmental level in ASD children. In the clinic, sleep assessment should be included in the routine of ASD visits, and during the intervention, sleep hygiene education is as important as the treatment of biological factors.Trial registrationThe study was approved by the ethics committee of the Children's Hospital of Chongqing Medical University, Approval Number: (2018) IRB (STUDY) NO. 121, and registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2000031194 ).