Dataset Information

Pediatric Prolonged-Release Melatonin for Sleep in Children with Autism Spectrum Disorder: Impact on Child Behavior and Caregiver's Quality of Life.

ABSTRACT: A randomized, 13-weeks, placebo-controlled double-blind study in 125 subjects aged 2-17.5 years with Autism Spectrum Disorder or Smith-Magenis syndrome and insomnia demonstrated efficacy and safety of easily-swallowed prolonged-release melatonin mini-tablets (PedPRM; 2-5 mg) in improving sleep duration and onset. Treatment effects on child behavior and caregiver's quality of life were evaluated. PedPRM treatment resulted in significant improvement in externalizing but not internalizing behavior (Strengths and Difficulties questionnaire; SDQ) compared to placebo (p?=?0.021) with clinically-relevant improvements in 53.7% of PedPRM-treated versus 27.6% of placebo-treated subjects (p?=?0.008). Caregivers' quality of life also improved with PedPRM versus placebo (p?=?0.010) and correlated with the change in total SDQ (p?=?0.0005). PedPRM alleviates insomnia-related difficulties, particularly externalizing behavior in the children, subsequently improving caregivers' quality of life.

SUBMITTER: Schroder CM

PROVIDER: S-EPMC6647439 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Pediatric Prolonged-Release Melatonin for Sleep in Children with Autism Spectrum Disorder: Impact on Child Behavior and Caregiver's Quality of Life.

Schroder Carmen M CM Malow Beth A BA Maras Athanasios A Melmed Raun D RD Findling Robert L RL Breddy John J Nir Tali T Shahmoon Shiri S Zisapel Nava N Gringras Paul P

Journal of autism and developmental disorders 20190801 8

A randomized, 13-weeks, placebo-controlled double-blind study in 125 subjects aged 2-17.5 years with Autism Spectrum Disorder or Smith-Magenis syndrome and insomnia demonstrated efficacy and safety of easily-swallowed prolonged-release melatonin mini-tablets (PedPRM; 2-5 mg) in improving sleep duration and onset. Treatment effects on child behavior and caregiver's quality of life were evaluated. PedPRM treatment resulted in significant improvement in externalizing but not internalizing behavior ...[more]

PMID: 31079275

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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:INTRODUCTION:Melatonin, secreted by the pineal gland during the night phase, is a regulator of the biological clock and sleep tendency. Totally blind subjects frequently report severe, periodic sleep problems, with 50%-75% of cases displaying non-24-hour sleep-wake disorder (N24HSWD) due to inability to synchronize with the environmental day-night cycle. Melatonin immediate-release preparations are reportedly effective in N24HSWD. Here, we studied the efficacy and safety of prolonged-release melatonin (PRM), a registered drug for insomnia, for sleep disorders in totally blind subjects living in normal social environments. The primary endpoint was demonstration of clinically meaningful effects on sleep duration (upper confidence interval [CI] limit >20 minutes whether significant or not) to allow early decision-making on further drug development in this indication. TRIAL REGISTRATION:ClinicalTrials.gov registry - NCT00972075. METHODS:In a randomized, double-blind, placebo-controlled proof-of-principle study, 13 totally blind subjects had 2 weeks' placebo run-in, 6 weeks' randomized (1:1) PRM (Circadin(®)) or placebo nightly, and 2 weeks' placebo run-out. Outcome measures included daily voice recorded sleep diary, Clinical Global Impression of Change (CGIC), WHO-Five Well-being Index (WHO-5), and safety. RESULTS:Mean nightly sleep duration improved by 43 minutes in the PRM and 16 minutes in the placebo group (mean difference: 27 minutes, 95% CI: -14.4 to 69 minutes; P=0.18; effect size: 0.82) meeting the primary endpoint. Mean sleep latency decreased by 29 minutes with PRM over placebo (P=0.13; effect size: 0.92) and nap duration decreased in the PRM but not placebo group. The variability in sleep onset/offset and latency tended to decrease during PRM but not placebo treatment. The potentially beneficial effects of PRM persisted during the 2 weeks of discontinuation period, consistent with clock stabilizing effects. PRM was well-tolerated, adverse events were of mild or moderate severity and similar between PRM and placebo. CONCLUSION:Nightly use of PRM may potentially improve patient-reported sleep difficulties in totally blind individuals trying to adhere to normal social lifestyle. A larger study powered to demonstrate a statistically significant effect is warranted.

Dataset Information

Pediatric Prolonged-Release Melatonin for Sleep in Children with Autism Spectrum Disorder: Impact on Child Behavior and Caregiver's Quality of Life.

Publications

Pediatric Prolonged-Release Melatonin for Sleep in Children with Autism Spectrum Disorder: Impact on Child Behavior and Caregiver's Quality of Life.

Similar Datasets

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