Pilot Study of Sleep Therapy and Biomarkers in Children With Autism Spectrum Disorders

Autism Spectrum Disorder Clinical Trial

Official title:

Pilot Study of Sleep Therapy and Biomarkers in Children With Autism Spectrum Disorders

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02487082
• Other study ID #: 65708
• Status: Terminated
• Phase: Phase 2
• Start date: June 2015
• Est. completion date: January 29, 2021

Study information

• Verified date: May 2024
• Source: Stony Brook University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to test the combined effect of melatonin and donepezil on improving sleep and behavior in children with Autism Spectrum Disorders. Melatonin is a natural neurohormone that helps regulate sleep and wake cycles. Donepezil is used to improve mental function for people with Alzheimer's disease. Children with Autism Spectrum Disorders are more likely to have problems sleeping than other children. This difficulty has been linked to daytime behavioral problems and family stress.

Description:

The goal of the present exploratory investigation is to see if there is a suggestion of a large additive or synergistic effect of melatonin and donepezil given together. Individually both medications improve sleep, but appear do so in different ways, with melatonin altering circadian rhythm and donepezil altering the characteristics of REM sleep. In this pilot investigation we will examine whether their combined effects on sleep lead to a large improvement in the behavior of children with ASD. Combined pharmacotherapy is very common in clinical practice, but is rarely studied in research (Comer et al. 2010). These two medications are both well tolerated and there is no negative drug interaction between the two. This investigation will use an RCT as well as a set of exploratory analyses to assess the combined effects of these two medications compared to placebo in terms of behavioral and sleep measures. In addition we will collect exploratory biomarkers (e.g., digit ratio, the ratio of the lengths different fingers as a measure of the balance of sex hormones during embryonic development) to relate to the various sleep and behavioral measures. A positive signal from this study may be used to guide a follow-up study with greater numbers of study subjects and statistical power.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: January 29, 2021
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 17 Years

Eligibility

Inclusion Criteria:

• Both male and female children

• Ages 4 to 17 1/2 years

• Diagnosis with Autism Spectrum Disorder on the basis of the clinical judgment of an autism specialist, preferably using the Autism Diagnostic Observation Schedule or the Autism Diagnostic Interview-Revised.

Exclusion Criteria:

• Abnormal electroencephalogram in the past month

• Cardiovascular problems

• Asthma

• Respiratory disease

• Peptic ulcer disease

• Renal or hepatic dysfunction (abnormal blood urea nitrogen/creatinine or 2 times elevated liver transaminases)

• Urinary tract obstruction

• Underweight (body mass index < 5th percentile compared to age and sex matched population)

• Other serious illness

• Use of any of the following drugs that might interact with study medications (anticholinergics, systemic corticosteroids, phenobarbital, peginterferon, beta-blockers or any drug that may cause arrhythmias). Drugs that induce or inhibit cytochrome P450 2D6 and cytochrome P450 3A4 (enzymes important for drug metabolism) will be allowed because any effects of such medications are likely to be lost in individual variability due to genetic polymorphisms.

• Use of medications affecting sleep with a half-life of 7 days or more. [Children on medications affecting sleep with a half-life of less than 7 days (including melatonin and donepezil) are eligible if they agree to discontinue use for the duration of the trial.]

• Pregnancy and lactation

Related Conditions & MeSH terms

• Autism Spectrum Disorder
• Autistic Disorder
• Child Development Disorders, Pervasive

Intervention

Drug:
• Melatonin and Donepezil
10 weeks of active study medication in Group A during Phase 1 & Phase 2. 5 weeks of active study medication in Group B during Phase 2.

Other:
• Placebo
For both groups: 5 weeks of Placebo in the Run-In Phase. For Group B: an addition 5 weeks of Placebo in Phase 1.

Locations

Country	Name	City	State
United States	Stony Brook University	Stony Brook	New York

Sponsors (1)

Lead Sponsor	Collaborator
Stony Brook University

Country where clinical trial is conducted

United States, 

References & Publications (6)

Buckley AW, Sassower K, Rodriguez AJ, Jennison K, Wingert K, Buckley J, Thurm A, Sato S, Swedo S. An open label trial of donepezil for enhancement of rapid eye movement sleep in young children with autism spectrum disorders. J Child Adolesc Psychopharmacol. 2011 Aug;21(4):353-7. doi: 10.1089/cap.2010.0121. — View Citation

Cidav Z, Marcus SC, Mandell DS. Implications of childhood autism for parental employment and earnings. Pediatrics. 2012 Apr;129(4):617-23. doi: 10.1542/peds.2011-2700. Epub 2012 Mar 19. — View Citation

Malow BA, Marzec ML, McGrew SG, Wang L, Henderson LM, Stone WL. Characterizing sleep in children with autism spectrum disorders: a multidimensional approach. Sleep. 2006 Dec;29(12):1563-71. doi: 10.1093/sleep/29.12.1563. — View Citation

Richdale AL, Schreck KA. Sleep problems in autism spectrum disorders: prevalence, nature, & possible biopsychosocial aetiologies. Sleep Med Rev. 2009 Dec;13(6):403-11. doi: 10.1016/j.smrv.2009.02.003. Epub 2009 Apr 24. — View Citation

Taylor MA, Schreck KA, Mulick JA. Sleep disruption as a correlate to cognitive and adaptive behavior problems in autism spectrum disorders. Res Dev Disabil. 2012 Sep-Oct;33(5):1408-17. doi: 10.1016/j.ridd.2012.03.013. Epub 2012 Apr 21. — View Citation

Wasdell MB, Jan JE, Bomben MM, Freeman RD, Rietveld WJ, Tai J, Hamilton D, Weiss MD. A randomized, placebo-controlled trial of controlled release melatonin treatment of delayed sleep phase syndrome and impaired sleep maintenance in children with neurodevelopmental disabilities. J Pineal Res. 2008 Jan;44(1):57-64. doi: 10.1111/j.1600-079X.2007.00528.x. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Aberrant Behavior Checklist (ABC) Lethargy/Social Withdrawal Subscale	Subscale of the Aberrant Behavior Checklist (ABC). Subscales were derived by factor analysis (n=927).; The checklist was first developed for use with severely mentally retarded individuals. More recently it has become widely used in research with children with autism. The ABC checklist is considered sensitive to drug effects.; The Lethargy/Social Withdrawal subscale contains items such as: "Listless, sluggish, inactive" ; "Withdrawn, prefers solitary activities"; "Does not try to communicate by words or gestures"; "Shows few social reactions to others".; The subscale consists of 16 items, each rated on a 4 point scale (0 = not at all, 3 = severe). Possible scores range from 0 to 48. Higher scores mean more lethargy and/or more social withdrawal.	Subscale rating was made by parent/caregiver every 5 weeks for a total of 5 times. Due to small N, only the endpoint of the study is reported here. Study endpoint (Visit 5) was after at least 18 wks, including 2 wks of washout, up to a maximum of 27 wks.
Secondary	Aberrant Behavior Checklist (ABC) Stereotypic Behavior Subscale.	Subscale of the Aberrant Behavior Checklist (ABC). Subscales were derived by factor analysis (n=927).; The checklist was first developed for use with severely mentally retarded individuals. More recently it has become widely used in research with children with autism. The ABC Checklist is considered sensitive to drug effects.; The Stereotypic Behavior subscale contains items such as: "Meaningless, recurring body movements" ; "Odd, bizarre in behavior"; "Waves, shakes the extremities repeatedly"; "Rocks body back and forth".; The subscale consists of 7 items, each rated on a 4 point scale (0 = not at all, 3 = severe). Possible scores range from 0 to 21. Higher scores mean more stereotyped behavior.	Subscale rating was made by parent/caregiver every 5 weeks for a total of 5 times. Due to small N, only the endpoint of the study is reported here. Study endpoint (Visit 5) was after at least 18 wks, including 2 wks of washout, up to a maximum of 27 wks.
Secondary	Sleep Duration (Hours)	A brief seven item questionnaire adapted from the Children's Sleep Habits Questionnaire (CSHQ). This parental questionnaire assesses sleep behaviors in children. It has been validated in children with ASD, correlates with polysomnographic recordings, and has been used successfully in previous studies of melatonin with such children. The CSHQ items chosen for this study come from the subscales found to be most often disturbed in children with autism.	Rating was made by parent/caregiver every 5 weeks for a total of 5 times. Due to small N, only the endpoint of the study is reported here. Study endpoint (Visit 5) was after at least 18 wks, including 2 wks of washout, up to a maximum of 27 wks.
Secondary	Clinical Global Impressions Scale, Clinician Impression of Global Improvement	Measured by the Clinical Global Impressions Scale. The Clinician Impression of Global Improvement is a single item rated as follows: 1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; 7 = very much worse. Thus, higher scores indicate a change for the worse. Note: This measure was not evaluated at Baseline.	Rating was made by clinician every 5 weeks for a total of 5 times. Due to small N, only the endpoint of the study is reported here. Study endpoint (Visit 5) was after at least 18 wks, including 2 wks of washout, up to a maximum of 27 wks.
Secondary	Clinical Global Impressions Scale, Parent Reported Global Improvement	Parent Impression of Global Improvement is a single item rated as follows: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse. Thus, higher scores indicate a change for the worse. Note: This measure was not evaluated at Baseline.	Rating was made by parent every 5 weeks for a total of 5 times. Due to small N, only the endpoint of the study is reported here. Study endpoint (Visit 5) was after at least 18 wks, including 2 wks of washout, up to a maximum of 27 wks.