AutismPhase 2NCT05501678
Trial of Diphenhydramine for Sleep in Children With Autism
A Phase 2 study testing Diphenhydramine in people with Autism and Autism Spectrum Disorder, run by Stanford University at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 8 to 17 years
- Conditions the study is for
- Autism, Autism Spectrum Disorder
- What is being tested?
- Diphenhydramine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Aug 2023to 31 Dec 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
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- 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).
Who cannot join
- 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
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- 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).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Stanford University
Stanford, California, 94305-5719
Ryan Villacrucis, (650) 736-1235, acesleepstudy@stanford.edu
Robin Libove, (650) 736-1235, rlibove@stanford.edu
About this study
Official title: Randomized Placebo-controlled Crossover Trial of Diphenhydramine for Sleep in Children With Autism
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.
- Conditions
- Autism, Autism Spectrum Disorder
- Being tested
- Diphenhydramine, Placebo
- Keywords
- Diphenhdramine, Sleep, clinical trial, autism
- Medical subject headings
- Autistic Disorder, Autism Spectrum Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DiphenhydramineDrug
Also called Benadryl
25mg (and up to 50mg) Diphenhydramine given orally
PlaceboDrug
Matching Placebo given orally
| Study group | Role | What they receive |
|---|---|---|
| Diphenhydramine, then Placebo | Experimental | Participants will first receive Diphenhydramine for a 4-week period. A 25 mg dose of Diphenhydramine will be given at bedtime for one week and then will increase to 50 mg if needed and if well tolerated.
Participants will then receive Placebo (fake tablet) for a 4-week period. A 25 mg dose of matching Placebo will be given at bedtime for one week and then will increase to 50 mg if needed and if well tolerated. Receives: Drug: Diphenhydramine; Drug: Placebo |
| Placebo, then Diphenhydramine | Experimental | Participants will first receive Placebo (fake tablet) for a 4-week period. A 25 mg dose of matching Placebo will be given at bedtime for one week and then will increase to 50 mg if needed and if well tolerated.
Participants will then receive Diphenhydramine for a 4-week period. A 25 mg dose of Diphenhydramine will be given at bedtime for one week and then will increase to 50 mg if needed and if well tolerated. Receives: Drug: Diphenhydramine; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in sleep latency as measured by polysomnography (PSG) and/or actigraphy
Measured: Baseline, Week 4 and Week 8
Change from baseline in duration of non-rapid eye movement (NREM) sleep as measured by polysomnography (PSG)
Measured: Baseline, Week 4 and Week 8
Secondary outcomes (1)
Change from baseline in sleep efficiency as measured by polysomnography (PSG) and actigraphy
Measured: Baseline, Week 4 and Week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2022
- Study start9 Aug 2023
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AutismStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 26 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Responsible party
- Principal investigator, Antonio Hardan, Stanford University
- Investigators
- Antonio Y. Hardan, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05501678
- Sponsor's protocol ID
- IRB-66941
- Other IDs
- 1P50HD109861
- Status last verified
- Mar 2026
- First submitted
- 12 Aug 2022
- Last updated
- 27 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: We will submit de-identified clinical data to the NIMH Data Archive (NDA) data repository.
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Placebo-controlled Crossover Trial of Diphenhydramine for Sleep in Children With Autism
- ClinicalTrials.gov ID
- NCT05501678
- Acronym / sponsor ID
- IRB-66941
- Conditions
- Autism, Autism Spectrum Disorder
- Keywords
- Diphenhdramine, Sleep, clinical trial, autism
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 26 participants (estimated)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- 9 Aug 2023 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 15 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Diphenhydramine, then Placebo | Experimental | Drug: Diphenhydramine, Drug: PlaceboParticipants will first receive Diphenhydramine for a 4-week period. A 25 mg dose of Diphenhydramine will be given at bedtime for one week and then will increase to 50 mg if needed and if well tolerated. Participants will then receive Placebo (fake tablet) for a 4-week period. A 25 mg dose of matching Placebo will be given at bedtime for one week and then will increase to 50 mg if needed and if well tolerated. |
| Placebo, then Diphenhydramine | Experimental | Drug: Diphenhydramine, Drug: PlaceboParticipants will first receive Placebo (fake tablet) for a 4-week period. A 25 mg dose of matching Placebo will be given at bedtime for one week and then will increase to 50 mg if needed and if well tolerated. Participants will then receive Diphenhydramine for a 4-week period. A 25 mg dose of Diphenhydramine will be given at bedtime for one week and then will increase to 50 mg if needed and if well tolerated. |
Who may qualify
- Ages
- 8 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (11 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DiphenhydramineAlso: Benadryl25mg (and up to 50mg) Diphenhydramine given orally | Drug | Diphenhydramine, then Placebo, Placebo, then Diphenhydramine |
| PlaceboMatching Placebo given orally | Drug | Diphenhydramine, then Placebo, Placebo, then Diphenhydramine |
Primary outcome
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
1 secondary outcome
Change from baseline in sleep efficiency as measured by polysomnography (PSG) and actigraphy
Time frame: Baseline, Week 4 and Week 8
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2026.
- Individual participant dataSharing planned: Yes. We will submit de-identified clinical data to the NIMH Data Archive (NDA) data repository.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Antonio Y. Hardan, MD principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Diphenhydramine in people with Autism and Autism Spectrum Disorder, run by Stanford University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ryan Villacrucis ((650)736-1235, acesleepstudy@stanford.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in sleep latency as measured by polysomnography (PSG) and/or actigraphy (time frame: Baseline, Week 4 and Week 8). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2026.