Trial of Zolpidem for Sleep in Children With Autism

Study Overview
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Brief Summary
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The purpose of this study is to examine the effect of zolpidem on sleep in children and adolescents with Autism Spectrum Disorder (ASD). Zolpidem is a nonbenzodiazepine GABAa receptor agonist drug that acts as a hypnotic. To accomplish this, the investigators will use a randomized double-blind placebo-controlled crossover 8-week study design to examine the effect of zolpidem on sleep physiology as assessed by polysomnography (PSG), actigraphy, circadian rhythm, and clinical measures.

Official Title
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Randomized Placebo-Controlled Crossover Trial of Zolpidem for Sleep in Children With Autism

Conditions
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Autism, Autism Spectrum Disorder

Intervention / Treatment
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* Drug: Zolpidem
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Participants will meet the following Outpatients between 8 and 17 years of age with only 12 to 17 years of age during year 1 Diagnostic and Statistical Manual, 5th edition (DSM-5) criteria for Autism Spectrum Disorder (ASD) on the basis of clinical evaluation, confirmed with the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule, 2nd Ed (ADOS-2) Males and females Availability of polysomnography (PSG) and actigraphy data 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 care provider who can reliably bring participant to clinic visits, provide trustworthy ratings, and interacts with participant on a regular basis stable medications for at least 4 weeks no planned changes in psychosocial and biomedical interventions during the trial willingness to provide additional saliva samples and participate in key study procedures (i.e., safety measurements every visit, PSG at weeks 4 and 8, and wear the actigraphy watch for 2 weeks before the beginning of trial as well as during the 8 weeks of the trial) requirement of dual protection contraception use in females who are sexually active and are of childbearing potential. Dual use contraceptive methods involve the use of both a hormonal method (oral contraceptives, long-acting reversible contraceptives, etc.) and a barrier method (condoms). Exclusion criteria: Participants will be excluded if one or more of the following is met active suicidal ideation or DSM-5 diagnosis of schizophrenia, schizoaffective disorder, or psychotic disorder active medical problems: migraine, asthma, seizure disorder, significant physical illness (e.g., anaphylaxis, serious liver, renal, or cardiac pathology), and hepatic insufficiency evidence of a genetic mutation known to cause autism or intellectual disability (e.g., Fragile X Syndrome), metabolic, or infectious etiology for the participant's autism on the basis of medical history, neurologic history, and available tests for inborn errors of metabolism and chromosomal analysis pregnant or sexually active females not using a reliable method of contraception (urinary tests for pregnancy will be employed in this study) individuals taking beta-blockers (local or systemic), benzodiazepines, antiepileptic medications, serotonin selective re-uptake inhibitors, melatonin, antihistamines and antidepressants history of hypersensitivity to zolpidem history of severe side effects from zolpidem history of adequate trial of zolpidem current use of any medications known to interact with zolpidem such as medications inhibiting CYP3A4 and CYP1A2 history of complex sleep-related behaviors individuals using alcohol, marijuana and other substances.

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zolpidem, then Placebo<br>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. | Drug: Zolpidem<br>* 5mg (and up to10mg) Diphenhydramine given orally<br>* Other names: Ambien;Drug: Placebo<br>* Matching Placebo given orally<br>|
| Experimental: Placebo, then Zolpidem<br>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. | Drug: Zolpidem<br>* 5mg (and up to10mg) Diphenhydramine given orally<br>* Other names: Ambien;Drug: Placebo<br>* Matching Placebo given orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in sleep architecture as measured by polysomnography (PSG), examples include sleep latency and non-rapid eye movement (NREM) |  | Baseline, Week 4 and Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in sleep efficiency as measured by actigraphy |  | Baseline, Week 4 and Week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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zolpidem, sleep, clinical trial, autism