Trial of Diphenhydramine for Sleep in Children With Autism

NCT ID: NCT05501678

Last Updated: 2025-11-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-08-09
• Study Completion Date: 2027-12-31

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

Keywords

Diphenhdramine; Sleep; clinical trial; autism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Diphenhydramine

Intervention Type: DRUG

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

Placebo

Intervention Type: DRUG

Matching Placebo given orally

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.

Group Type: EXPERIMENTAL

Diphenhydramine

Intervention Type: DRUG

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

Placebo

Intervention Type: DRUG

Matching Placebo given orally

Interventions

Diphenhydramine

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

Intervention Type: DRUG

Placebo

Matching Placebo given orally

Intervention Type: DRUG

Other Intervention Names

Benadryl

Eligibility Criteria

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)
• 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 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).

• Minimum Eligible Age: 8 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Antonio Hardan

Professor of Psychiatry and Behavioral Sciences

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Antonio Y. Hardan, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University

Stanford, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Ryan Villacrucis

Role: CONTACT

Phone: (650)736-1235

Email: acesleepstudy@stanford.edu

Robin Libove

Role: CONTACT

Phone: (650)736-1235

Email: rlibove@stanford.edu

Facility Contacts

Ryan Villacrucis

Role: primary

Robin Libove

Role: backup

Other Identifiers

1P50HD109861

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB-66941

Identifier Type: -

Identifier Source: org_study_id