Recruiting
Phase 2

Diphenhydramine

Sponsor:

Stanford University

Code:

NCT05501678

Conditions

Autism

Autism Spectrum Disorder

Eligibility Criteria

Sex: All

Age: 8 - 17

Healthy Volunteers: Not accepted

Interventions

Diphenhydramine

Placebo

Study Details

Brief 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. 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

Study ID

NCT05501678

Start date

Aug 9, 2023

Status verified date

Mar, 2026

Completion date

Dec 31, 2027

Anticipated

Primary completion date

Dec 31, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 8 - 17

Healthy Volunteers: Not accepted

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).

Study Design

Enrollment

26 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

experimental: Diphenhydramine, then Placebo

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.

experimental: Placebo, then Diphenhydramine

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.

Interventions

Diphenhydramine

25mg (and up to 50mg) Diphenhydramine given orally

Placebo

Matching Placebo given orally

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 ]
  • 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 ]

Central Contacts and Locations

Central contacts

Ryan Villacrucis

(650)736-1235acesleepstudy@stanford.edu

Robin Libove

(650)736-1235rlibove@stanford.edu

Locations

Stanford University

Recruiting

Stanford, California, United States, 94305-5719

Contacts

Ryan Villacrucis

(650) 736-1235acesleepstudy@stanford.edu

Robin Libove

(650) 736-1235rlibove@stanford.edu

Principal Investigator:

Antonio Y. Hardan, MD

More Information

Sponsor

Stanford University

Last update posted

Mar 27, 2026

Last verified

Mar, 2026

Keywords

  • Diphenhdramine
  • Sleep
  • clinical trial
  • autism

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Stanford University on 2026-03-27.