A Trial of the Drug Donepezil for Sleep Enhancement and Behavioral Change in Children With Autism

NCT01887132 | Terminated Phase 2 Results

• 2 other identifiers: 13016413-M-0164
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Some children with autism spectrum disorders (ASD) do not have normal sleep cycles. Some of these children spend very little time in the rapid eye movement (REM) stage of sleep. Some studies suggest that less time in REM sleep can be associated with learning and behavior problems. Donepezil is a medication used to treat Alzheimer s disease. Donepezil can increase REM sleep in some adults with different disorders. A small study showed that Donepezil can also increase REM sleep in children with ASD. Researchers now want to see if Donepezil can improve communication skills and social interaction in children with ASD. They also want to see if any change in symptoms seems to come from changes in REM sleep. Objectives: \- To see if a medication, Donepezil, can improve the way communication skills and social interaction develop in young children with autism spectrum disorders. Eligibility: \- Children 22 to 44 months of age with ASD. Design:

• Participants will be screened with a blood test, heart tests, and a sleep study. During the sleep study, children will sleep in a darkened room for 2 nights with electrodes on their body and a tube under their nose. Parents can sleep in the room with their child. A technician will monitor the room all night.
• Participants will take the study medication once a day.
• Treatment will be monitored at visits every 3 months. At each visit the participant will take blood tests, heart tests, or behavior tests. Participants will have 2 more sleep studies.
• Participation will end after 18 months.

Conditions

Autism Spectrum Disorders

Keywords

Sleep Architecture; Autism; Language Development

Outcome Measures

Primary Outcomes (1)

• Nonverbal Developmental Quotient (NVDQ)

  The Nonverbal Developmental Quotient (NVDQ) was calculated from the Mullen Scales of Early Learning scores by dividing the nonverbal mental age (average of the age equivalent value for the Visual Reception and Fine Motor scores) by the chronological age in months. The NVDQ is normalized to a mean score of 100, which indicates an average normal IQ. Less than 100 is a lower than average IQ. 2 standard deviations below average is considered "impaired" IQ (approximately lower than 70).

  Baseline and 12 months

Secondary Outcomes (1)

• REM Percentage at Baseline, 6, 12 and 18 Months

  Baseline, 6, 12 and 18 months

Other Outcomes (4)

• An Exploratory Analysis Will Investigate Whether Normalization of REM Parameters Also Improves Other Measurements of Sleep Quality in Children With Autism.

  12 months

• Mullen Scales at 18 Months

  18 months

• Autism Diagnostic Observation Schedule (ADOS) at 6, 12 and 18 Months

  6, 12 and 18 months

Study Arms (3)

Open-Label Donepezil

EXPERIMENTAL

Drug: Donepezil

Donepezil - Blinded

EXPERIMENTAL

Drug: Donepezil

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Donepezil DRUG

Donepezil - Blinded; Open-Label Donepezil

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 24 Months - 50 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Diagnosis of an Autism Spectrum Disorder (DSM-IV diagnoses of autistic disorder or Pervasive Developmental Disorder, Not Otherwise Specified).
• Male or Female subjects between the ages of 24 and 50 months.
• Language scores (from the Mullen Scales of Early Learning) that are at least 1.5 SD lower than the mean.
• \. Each legal guardian must have a level of understanding sufficient to agree to all required tests and examinations. Each legal guardian must understand the nature of the study.
• \. Each subject must be stable for at least 6 weeks on any medication or therapy regimen prior to entry into study and must have no newly (within 6 weeks) recognized or intolerable adverse effects from that medicine or therapy. No subjects will be asked to discontinue any medication in order to qualify for enrollment but subjects taking contraindicated drugs will not qualify for enrollment.
• \. Demonstrated REM% two standard deviations or more below the normative values for age for the randomized controlled trial part.
• \. English language is primarily spoken at home.

You may not qualify if:

• Serious, unstable illnesses including gastroenterologic, respiratory, cardiovascular endocrinologic, immunologic, or hematologic disease.
• Renal or hepatic dysfunction that would interfere with excretion or metabolism of donepezil as evidenced by increase above upper limits of normal for BUN/creatinine, or two-fold elevation of serum transaminases (ALT/SGPT, AST/SGOT) or gamma glutamate (GGT).
• Documented history of hypersensitivity or intolerance to donepezil or other piperidine derivative.
• Subjects must not be taking any medication known to affect REM sleep (or sleep
• architecture in general) or that is contraindicated for co-administration with donepezil.
• Presence or history of other unstable neurological disorders such as seizure disorders,
• metabolic disorders, narcolepsy or movement disorders.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Anderson DK, Lord C, Risi S, DiLavore PS, Shulman C, Thurm A, Welch K, Pickles A. Patterns of growth in verbal abilities among children with autism spectrum disorder. J Consult Clin Psychol. 2007 Aug;75(4):594-604. doi: 10.1037/0022-006X.75.4.594.

  PMID: 17663613 BACKGROUND

• Anderson DK, Oti RS, Lord C, Welch K. Patterns of growth in adaptive social abilities among children with autism spectrum disorders. J Abnorm Child Psychol. 2009 Oct;37(7):1019-34. doi: 10.1007/s10802-009-9326-0.

  PMID: 19521762 BACKGROUND

• Bliwise DL, Carroll JS, Lee KA, Nekich JC, Dement WC. Sleep and "sundowning" in nursing home patients with dementia. Psychiatry Res. 1993 Sep;48(3):277-92. doi: 10.1016/0165-1781(93)90078-u.

  PMID: 8272449 BACKGROUND

• Ure A, Cox GR, Haslam R, Williams K. Acetylcholinesterase inhibitors for autistic spectrum disorders. Cochrane Database Syst Rev. 2023 Jun 1;6(6):CD013851. doi: 10.1002/14651858.CD013851.pub2.

  PMID: 37267443 DERIVED

MeSH Terms

Conditions

Autism Spectrum Disorder; Autistic Disorder

Interventions

Donepezil

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds

Limitations and Caveats

Study terminated due to lack of recruitment. No conclusions regarding the use of donepezil can be drawn from small sample size data collection.

Results Point of Contact

• Title: Ashura W Buckley
• Organization: National Institute of Mental Health (NIMH)

shu.buckley@nih.gov

(301) 496-5190

Study Officials

• Ashura W Buckley, M.D.

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2013
• First Posted: June 26, 2013
• Study Start: June 1, 2013
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: September 25, 2017
• Results First Posted: September 25, 2017

Record last verified: 2017-09

Data Sharing

• IPD Sharing: Will share

Locations

US (1)