Zolpidem for Sleep Disturbances in Children with Autism

Overseen by Antonio Hardan, MD

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Stanford University

Must not be taking: Beta-blockers, Benzodiazepines, Antidepressants, others

Disqualifiers: Schizophrenia, Seizure disorder, Liver pathology, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing zolpidem, a medication that helps people fall asleep, in children and adolescents with Autism Spectrum Disorder (ASD). These children often have trouble sleeping, and typical treatments may not work for them. Zolpidem works by calming the brain, making it easier to fall asleep. Zolpidem is a medication commonly used to treat sleep problems by helping people fall asleep, and it has been studied in various populations including healthy adults and those with insomnia.

Will I have to stop taking my current medications?

The trial requires that participants do not take certain medications, including beta-blockers, benzodiazepines, antiepileptic medications, melatonin, antihistamines, and antidepressants. If you are on any of these, you would need to stop taking them to participate.

How does the drug Zolpidem differ from other treatments for sleep disturbances in children with autism?

Zolpidem, commonly known as Ambien, is a medication typically used for short-term treatment of insomnia in adults, and its use in children with autism is less common compared to melatonin, which has shown effectiveness in improving sleep latency and duration in this population. Unlike melatonin, which is a natural hormone, Zolpidem is a sedative that works by affecting chemicals in the brain to promote sleep, but it has not been widely studied or proven effective for sleep issues in children with autism. ^{1 2 3 4 5}

Research Team

Antonio Hardan, MD

Principal Investigator

Stanford University

Eligibility Criteria

This trial is for children and adolescents aged 8-17 with Autism Spectrum Disorder who have sleep disturbances. They must not be on certain medications, have stable medication use for the past 4 weeks, and meet specific autism diagnostic criteria. Sexually active females must use dual contraception.

Inclusion Criteria

Meet DSM-5 criteria for Autism Spectrum Disorder (ASD) confirmed with ADI-R and ADOS-2

Sleep disturbances as assessed using Children's Sleep Habits Questionnaire (CSHQ) with a score of 41 or higher and sleep efficiency of 80% or less

Willingness to provide additional saliva samples and participate in key study procedures

Exclusion Criteria

I am taking medications that interact with zolpidem.

History of hypersensitivity to zolpidem

I do not have active thoughts of suicide or a diagnosis of schizophrenia, schizoaffective, or psychotic disorder.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Zolpidem or Placebo in a crossover design for 8 weeks, with each treatment lasting 4 weeks

8 weeks

Weekly visits for monitoring and dose adjustments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo (Behavioural Intervention)
• Zolpidem (GABAa Receptor Agonist)

Trial Overview The study tests Zolpidem's effect on sleep in kids with ASD using a double-blind method where neither doctors nor participants know who gets Zolpidem or placebo. It involves sleep studies, wearing an activity watch, and no changes in treatments during the trial.

Participant Groups

Group I: Zolpidem, then Placebo Experimental Treatment 2 Interventions

Participants will first receive Zolpidem for a 4-week period. A 5 mg dose of Zolpidem will be given at bedtime for one week and then will increase to 10 mg if needed and if well tolerated. Participants will then receive Placebo (fake tablet) for a 4-week period. A 5 mg dose of matching Placebo will be given at bedtime for one week and then will increase to 10 mg if needed and if well tolerated.

Group II: Placebo, then Zolpidem Experimental Treatment 2 Interventions

Participants will first receive Placebo (fake tablet) for a 4-week period. A 5 mg dose of matching Placebo will be given at bedtime for one week and then will increase to 10 mg if needed and if well tolerated. Participants will then receive Zolpidem for a 4-week period. A 5 mg dose of Zolpidem will be given at bedtime for one week and then will increase to 10 mg if needed and if well tolerated.

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Dr. Richard A. Miller

Stanford University

Chief Executive Officer since 2023

Stanford University, MD

Dr. Robert Schott

Stanford University

Chief Medical Officer since 2021

University of Michigan, MD

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Dr. Jeanne Marrazzo

National Institutes of Health (NIH)

Chief Medical Officer

MD from University of California, Los Angeles

Dr. Jay Bhattacharya

National Institutes of Health (NIH)

Chief Executive Officer

MD, PhD from Stanford University

Findings from Research

About two-thirds of children with autism spectrum disorder (ASD) experience chronic insomnia, highlighting a significant issue in this population.

Effective strategies for improving sleep in children with ASD include sleep education, environmental modifications, behavioral interventions, and the use of melatonin, as outlined in a practice pathway developed by the Autism Treatment Network.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleep in Children with Autism Spectrum Disorder. Souders, MC., Zavodny, S., Eriksen, W., et al.[2022]

In a 14-week study involving 24 children with autism spectrum disorders, supplemental melatonin significantly improved sleep onset latency, showing effectiveness as early as the first week and maintaining benefits over several months.

The treatment was well tolerated and safe, leading to improvements not only in sleep but also in behavior and parenting stress, supporting the potential for larger randomized trials in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melatonin for sleep in children with autism: a controlled trial examining dose, tolerability, and outcomes. Malow, B., Adkins, KW., McGrew, SG., et al.[2022]

A pilot study involving 17 children with autism and insomnia showed that an 8-session cognitive behavioral treatment for childhood insomnia (CBT-CI) significantly improved both child and parent sleep, as well as reduced challenging behaviors like irritability and hyperactivity.

Parents reported that CBT-CI was helpful and suitable for their children, indicating that this treatment is feasible and promising for addressing insomnia in school-aged children with autism, warranting further research through randomized controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive behavioral treatment of insomnia in school-aged children with autism spectrum disorder: A pilot feasibility study. McCrae, CS., Chan, WS., Curtis, AF., et al.[2020]

Melatonin was found to significantly improve sleep latency and duration in children, especially those with autism or other neurodevelopmental disorders, based on a review of 22 randomized controlled trials involving 1758 children.

Pharmacologic treatments like zolpidem and eszopiclone showed limited efficacy for sleep improvement in children with ADHD, with some adverse events reported, indicating that melatonin may be a safer and more effective option for managing sleep disorders in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacologic Treatments for Sleep Disorders in Children: A Systematic Review. McDonagh, MS., Holmes, R., Hsu, F.[2020]

In a study of 107 children with autism spectrum disorders, melatonin was found to be a safe and well-tolerated treatment for insomnia, with 25% of parents reporting that sleep was no longer a concern after treatment.

The majority of parents (60%) noted improved sleep with melatonin, and there were minimal side effects, such as mild morning sleepiness, with no increase in seizure activity among children with epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melatonin for insomnia in children with autism spectrum disorders. Andersen, IM., Kaczmarska, J., McGrew, SG., et al.[2013]

References

1. United States pubmed.ncbi.nlm.nih.gov

Sleep in Children with Autism Spectrum Disorder. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Melatonin for sleep in children with autism: a controlled trial examining dose, tolerability, and outcomes. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Cognitive behavioral treatment of insomnia in school-aged children with autism spectrum disorder: A pilot feasibility study. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Pharmacologic Treatments for Sleep Disorders in Children: A Systematic Review. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Melatonin for insomnia in children with autism spectrum disorders. [2013]