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Trial of Diphenhydramine for Sleep in Children With Autism

Primary Purpose

Autism, Autism Spectrum Disorder

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Diphenhydramine
Placebo
Sponsored by
Stanford University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Autism focused on measuring Diphenhdramine, Sleep, clinical trial, autism

Eligibility Criteria

8 Years - 17 Years (Child)All SexesDoes not accept 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) and 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 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).

Sites / Locations

  • Stanford UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Diphenhydramine, then Placebo

Placebo, then Diphenhydramine

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
August 12, 2022
Last Updated
September 5, 2023
Sponsor
Stanford University
Collaborators
National Institutes of Health (NIH)
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1. Study Identification

Unique Protocol Identification Number
NCT05501678
Brief Title
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

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 9, 2023 (Actual)
Primary Completion Date
December 31, 2026 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Stanford University
Collaborators
National Institutes of Health (NIH)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. 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, 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autism, Autism Spectrum Disorder
Keywords
Diphenhdramine, Sleep, clinical trial, autism

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
26 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Diphenhydramine, then Placebo
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo, then Diphenhydramine
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Diphenhydramine
Other Intervention Name(s)
Benadryl
Intervention Description
25mg (and up to 50mg) Diphenhydramine given orally
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching Placebo given orally
Primary Outcome Measure Information:
Title
Change from baseline in sleep latency as measured by polysomnography (PSG)
Time Frame
Baseline, Week 4 and Week 8
Title
Change from baseline in duration of non-rapid eye movement (NREM) sleep as measured by polysomnography (PSG)
Time Frame
Baseline, Week 4 and Week 8
Secondary Outcome Measure Information:
Title
Change from baseline in sleep efficiency as measured by polysomnography (PSG) and actigraphy
Time Frame
Baseline, Week 4 and Week 8
Other Pre-specified Outcome Measures:
Title
Change from baseline on Children's Sleep Habits Questionnaire (CSHQ) subscale scores
Time Frame
Baseline, Week 4, Week 8
Title
Change from baseline on Aberrant Behavior Checklist, Second Edition (ABC-2) subscale scores
Time Frame
Baseline, Week 4, Week 8
Title
Change from baseline on Parent Sleep Habits Questionnaire Parent (PSHQ) scores
Time Frame
Baseline, Week 4, Week 8
Title
Change from baseline on Clinical Global Impression Scale (CGI) scores
Time Frame
Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, and Week 8
Title
Change from baseline on Child Behavior Checklist (CBCL) scores
Time Frame
Baseline, Week 4, Week 8
Title
Change from baseline on Social Responsiveness Scale, Second Edition (SRS-2) scores
Time Frame
Baseline, Week 4, Week 8
Title
Change from baseline on Repetitive Behavior Scale - Revised (RBS-R) scores
Time Frame
Baseline, Week 4, Week 8
Title
Change from baseline on Sensory Profile Questionnaire (SPQ) scores
Time Frame
Baseline, Week 4, Week 8
Title
Change from baseline on Stanford Social Dimension Scale (SSDS) scores
Time Frame
Baseline, Week 4, Week 8
Title
Change from baseline on Dimensional Assessment of Repetitive Behaviors (DARB) scores
Time Frame
Baseline, Week 4, Week 8
Title
Change from baseline on NEuroPSYchological Assessment, 2nd Edition (NEPSY-2) Affect Recognition scores
Time Frame
Baseline, Week 4, Week 8

10. Eligibility

Sex
All
Minimum Age & Unit of Time
8 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility 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) and 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 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, 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).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Joe McGrath
Phone
(650)736-1235
Email
roscoe37@stanford.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Richard Ellks
Phone
(650)736-1235
Email
ACESleepTrials@stanford.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Antonio Y. Hardan, MD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University
City
Stanford
State/Province
California
ZIP/Postal Code
94305-5719
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joe McGrath
Phone
650-736-1235
Email
roscoe37@stanford.edu
First Name & Middle Initial & Last Name & Degree
Richard Ellks
Phone
(650) 736-1235
Email
ACESleepTrials@stanford.edu
First Name & Middle Initial & Last Name & Degree
Antonio Y. Hardan, MD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
We will submit de-identified clinical data to the NIMH Data Archive (NDA) data repository.
IPD Sharing URL
https://nda.nih.gov/nda/data-contribution.html

Learn more about this trial

Trial of Diphenhydramine for Sleep in Children With Autism

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