Trial of Diphenhydramine for Sleep in Children With Autism

Sponsor

Stanford University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05501678

Collaborator

National Institutes of Health (NIH) (NIH)

Enrollment

Arms

56.9

Anticipated Duration (Months)

Study Details

Study Description

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, 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.

Condition or Disease	Intervention/Treatment	Phase
Autism Autism Spectrum Disorder	Drug: Diphenhydramine Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

26 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Randomized Placebo-controlled Crossover Trial of Diphenhydramine for Sleep in Children With Autism

Anticipated Study Start Date :

Oct 1, 2022

Anticipated Primary Completion Date :

Jun 30, 2027

Anticipated Study Completion Date :

Jun 30, 2027

Arms and Interventions

Arm	Intervention/Treatment
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.	Drug: Diphenhydramine 25mg (and up to 50mg) Diphenhydramine given orally Other Names: Benadryl Drug: Placebo Matching Placebo given orally
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.	Drug: Diphenhydramine 25mg (and up to 50mg) Diphenhydramine given orally Other Names: Benadryl Drug: Placebo Matching Placebo given orally

Arm

Intervention/Treatment

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.

Drug: Diphenhydramine

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

Other Names:

Benadryl

Drug: Placebo

Matching Placebo given orally

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.

Drug: Diphenhydramine

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

Other Names:

Benadryl

Drug: Placebo

Matching Placebo given orally

Outcome Measures

Primary Outcome Measures

Change from baseline in sleep latency as measured by polysomnography (PSG) [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 Outcome Measures

Change from baseline in sleep efficiency as measured by polysomnography (PSG) and actigraphy [Baseline, Week 3, Week 4, Week 7 and Week 8]

Other Outcome Measures

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]
Change from baseline on Clinical Global Impression Scale (CGI) scores [Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, and Week 8]
Change from baseline on Child Behavior Checklist (CBCL) scores [Baseline, Week 4, Week 8]
Change from baseline on Social Responsiveness Scale, Second Edition (SRS-2) scores [Baseline, Week 4, Week 8]
Change from baseline on Repetitive Behavior Scale - Revised (RBS-R) scores [Baseline, Week 4, Week 8]
Change from baseline on Sensory Profile Questionnaire (SPQ) scores [Baseline, Week 4, Week 8]
Change from baseline on Stanford Social Dimension Scale (SSDS) scores [Baseline, Week 4, Week 8]
Change from baseline on Dimensional Assessment of Repetitive Behaviors (DARB) scores [Baseline, Week 4, Week 8]
Change from baseline on NEuroPSYchological Assessment, 2nd Edition (NEPSY-2) Affect Recognition scores [Baseline, Week 4, Week 8]

Eligibility Criteria

Criteria

Ages Eligible for Study:

8 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).