Trial of Diphenhydramine for Sleep in Children With Autism

• Status: Not yet recruiting
• Trial end date: 2027-06-30
• Target enrollment: 0
• Participant gender: All

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, we 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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Stanford University
• Collaborator: National Institutes of Health (NIH)
• Treatments: Diphenhydramine; Promethazine

Criteria

Inclusion criteria:

Participants will meet the following

• Outpatients between 8 and 17 years of age

• 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), actigraphy data, and saliva samples

• 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 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., PSG and actigraphy at week 4 and 8, and safety measurements every visit).

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 genetic mutation known to cause autism or intellectual disability (e.g., Fragile X Syndrome), 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 beta-blockers (local or systemic), benzodiazepines, antiepileptic medications, serotonin selective re-uptake inhibitors, 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).