NCT05501678 · Stanford University
Trial of Diphenhydramine for Sleep in Children With Autism
What this study is about
The purpose of this study is to examine the effect of diphenhydramine on sleep in children and adolescents with Autism Spectrum Disorder (ASD). Diphenhydramine is an anti-histaminergic agent with strong hypnotic properties.
View original scientific description
The purpose of this study is to examine the effect of diphenhydramine on sleep in children and adolescents with Autism Spectrum Disorder (ASD). Diphenhydramine is an anti-histaminergic agent with strong hypnotic properties. To accomplish this, the investigators will use a randomized double-blind placebo-controlled crossover 8-week study design to examine the effect of diphenhydramine on sleep physiology as assessed by polysomnography (PSG), actigraphy, circadian rhythm, and clinical measures.
Interventions
DRUG
Diphenhydramine
25mg (and up to 50mg) Diphenhydramine given orally
DRUG
Placebo
Matching Placebo given orally
Primary outcome measures
Change from baseline in sleep latency as measured by polysomnography (PSG) and/or actigraphy
Time frame: Baseline, Week 4 and Week 8
Change from baseline in duration of non-rapid eye movement (NREM) sleep as measured by polysomnography (PSG)
Time frame: Baseline, Week 4 and Week 8
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- Participants will meet the following
- Outpatients between 8 and 17 years of age at the time of consent
- 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) or the Childhood Autism Rating Scale, Second Edition (CARS-2).
- Males and females
- Availability of polysomnography (PSG) or actigraphy data
- Sleep disturbances as assessed using Children's Sleep Habits Questionnaire (CSHQ) with a score of 41 or higher
- 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 2 weeks, with the exception of Prozac which is required to be stable 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).
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)
- evidence of a 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 benzodiazepines, antiepileptic medications when prescribed for seizure disorder/epilepsy, melatonin and centrally-acting antihistamines
- history of hypersensitivity to diphenhydramine
- history of severe side effects from diphenhydramine
- history of adequate trial of diphenhydramine
- current use of any medications known to interact with diphenhydramine such as medications inhibiting CYP2D6
- taking anticholinergic agents (e.g., trihexyphenidyl, thioridazine).
Where
- Stanford, California
Collaborators
National Institutes of Health (NIH)
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Mar 27, 2026 · Source of record for eligibility and locations