Clinical trial NCT05501678: Trial of Diphenhydramine for Sleep in Children With Autism
Official title: Randomized Placebo-controlled Crossover Trial of Diphenhydramine for Sleep in Children With Autism
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Autism
Autism Spectrum Disorder
Keywords: Diphenhdramine
Sleep
clinical trial
autism
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
First posted: 2022-08-15
Enrollment: 26
Sex: ALL
Minimum age (years): 8
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


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 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, 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).

Primary outcomes:
measure: Change from baseline in sleep latency as measured by polysomnography (PSG)
timeFrame: Baseline, Week 4 and Week 8
measure: Change from baseline in duration of non-rapid eye movement (NREM) sleep as measured by polysomnography (PSG)
timeFrame: Baseline, Week 4 and Week 8
Secondary outcomes:
measure: Change from baseline in sleep efficiency as measured by polysomnography (PSG) and actigraphy
timeFrame: Baseline, Week 4 and Week 8
Other outcomes:
measure: Change from baseline on Children's Sleep Habits Questionnaire (CSHQ) subscale scores
timeFrame: Baseline, Week 4, Week 8
measure: Change from baseline on Aberrant Behavior Checklist, Second Edition (ABC-2) subscale scores
timeFrame: Baseline, Week 4, Week 8
measure: Change from baseline on Parent Sleep Habits Questionnaire Parent (PSHQ) scores
timeFrame: Baseline, Week 4, Week 8
measure: Change from baseline on Clinical Global Impression Scale (CGI) scores
timeFrame: Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, and Week 8
measure: Change from baseline on Child Behavior Checklist (CBCL) scores
timeFrame: Baseline, Week 4, Week 8
measure: Change from baseline on Social Responsiveness Scale, Second Edition (SRS-2) scores
timeFrame: Baseline, Week 4, Week 8
measure: Change from baseline on Repetitive Behavior Scale - Revised (RBS-R) scores
timeFrame: Baseline, Week 4, Week 8
measure: Change from baseline on Sensory Profile Questionnaire (SPQ) scores
timeFrame: Baseline, Week 4, Week 8
measure: Change from baseline on Stanford Social Dimension Scale (SSDS) scores
timeFrame: Baseline, Week 4, Week 8
measure: Change from baseline on Dimensional Assessment of Repetitive Behaviors (DARB) scores
timeFrame: Baseline, Week 4, Week 8
measure: Change from baseline on NEuroPSYchological Assessment, 2nd Edition (NEPSY-2) Affect Recognition scores
timeFrame: Baseline, Week 4, Week 8
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
Study officials:
affiliation: Stanford University
name: Antonio Y. Hardan, MD
role: PRINCIPAL_INVESTIGATOR
References: