Trial of Diphenhydramine for Sleep in Children With Autism

NCT05501678 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: IRB-669411P50HD109861
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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 Spectrum Disorder; Autism

Keywords

Diphenhdramine; Sleep; clinical trial; autism

Outcome Measures

Primary Outcomes (2)

• Change from baseline in sleep latency as measured by polysomnography (PSG) and/or actigraphy

  Baseline, Week 4 and Week 8

• Change from baseline in duration of non-rapid eye movement (NREM) sleep as measured by polysomnography (PSG)

  Baseline, Week 4 and Week 8

Secondary Outcomes (1)

• Change from baseline in sleep efficiency as measured by polysomnography (PSG) and actigraphy

  Baseline, Week 4 and Week 8

Other Outcomes (11)

• Change from baseline on Children's Sleep Habits Questionnaire (CSHQ) subscale scores

  Baseline, Week 4, Week 8

• Change from baseline on Aberrant Behavior Checklist, Second Edition (ABC-2) subscale scores

  Baseline, Week 4, Week 8

• Change from baseline on Parent Sleep Habits Questionnaire Parent (PSHQ) scores

  Baseline, Week 4, Week 8

Study Arms (2)

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.

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.

Drug: Diphenhydramine; Drug: Placebo

Interventions

Diphenhydramine DRUG

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

Also known as: Benadryl

Diphenhydramine, then Placebo; Placebo, then Diphenhydramine

Placebo DRUG

Matching Placebo given orally

Diphenhydramine, then Placebo; Placebo, then Diphenhydramine

Eligibility Criteria

• Age: 8 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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).

You may not qualify if:

• 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).

Sponsors & Collaborators

• Stanford University: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Stanford University

Stanford, California, 94305-5719, United States

RECRUITING

MeSH Terms

Conditions

Autistic Disorder; Autism Spectrum Disorder

Interventions

Diphenhydramine

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Ethylamines; Amines; Organic Chemicals; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Antonio Y. Hardan, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ryan Villacrucis

CONTACT

(650)736-1235; acesleepstudy@stanford.edu

Robin Libove

CONTACT

(650)736-1235; rlibove@stanford.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry and Behavioral Sciences

Study Record Dates

• First Submitted: August 12, 2022
• First Posted: August 15, 2022
• Study Start: August 9, 2023
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (1)