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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )
ClinicalTrials.gov Identifier:
NCT01887132
First received: June 22, 2013
Last updated: March 14, 2014
Last verified: December 2013
  Purpose

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.

Condition Intervention Phase
Autism Spectrum Disorders
Drug: Donepezil
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Randomized Controlled Trial of Donepezil for REM Enhancement and Behavioral Change in Autism

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • 12Either an improvement in the Expressive Language and the Receptive Language subscales of the Mullen Scales of Early Learning (MSEL)OR an improvement on the severity scale of the Autism Diagnostic Observation Schedule (ADOS). [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • An exploratory analysis will investigate whether normalization of REM parameters also improves other measurements of sleep quality in children with autism. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • The change in REM sleep parameters after 12 months in relation to improvements in behavioral indices. [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 90
Study Start Date: June 2013
Estimated Study Completion Date: September 2017
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Open-Label Donepezil Drug: Donepezil
N/A
Experimental: Donepezil - Blinded Drug: Donepezil
N/A
Placebo Comparator: Placebo Drug: Placebo
N/A

Detailed Description:

i. Objective

The objective of this study is to investigate the efficacy of donepezil to improve the developmental trajectory for core behavioral domains specific to autism, namely reciprocal social interaction and communication.

ii. Study population

90 children with an autism spectrum disorder between the ages of 24 to 50 months will be screened via polysomnogram to find 45 with a relative REM deficiency. This group will then be divided into two arms of drug versus placebo. Allowing for a 22 % drop out rate we expect 17 in each group to complete the study. Additionally, we will enroll 16 children with an ASD who do not meet criteria for relative REM deficiency in an open label arm to ascertain whether or not donepezil is beneficial to behavior in this group.

iii. Design

The proposal is for a 6 month treatment trial of 2.5 mg donepezil/placebo/day followed by 12 months of longitudinal follow-up. The primary study endpoint will be an examination of autism core symptoms and sleep architecture after 12 months.

iv. Outcome measures

The primary outcome measure will be:

An improvement in the Expressive Language and the Receptive Language subscales of the Mullen Scales of Early Learning (MSEL) at 12 months.

  1. Secondary outcome measures will be:

    An improvement in the Expressive Language and the Receptive Language subscales of the Mullen Scales at 18 months.

  2. An improvement on the severity scale of the Autism Diagnostic Observation Schedule (ADOS) at 6, 12 and 18 months.
  3. An improvement on the Vineland at 3, 6, 12 and 18 months
  4. We will also measure the change in REM sleep parameters after 6, 12 and 18 months in relation to improvements in behavioral indices.
  5. An exploratory analysis will investigate whether normalization of REM parameters also improves other measurements of sleep quality in children with autism.
  Eligibility

Ages Eligible for Study:   24 Months to 50 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

    1. Diagnosis of an Autism Spectrum Disorder (DSM-IV diagnoses of autistic disorder or Pervasive Developmental Disorder, Not Otherwise Specified).
    2. Male or Female subjects between the ages of 24 and 50 months.
    3. Language scores (from the Mullen Scales of Early Learning) that are at least 1.5 SD lower than the mean.

    5. 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.

    6. 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.

    7. Demonstrated REM% two standard deviations or more below the normative values for age for the randomized controlled trial part.

    8. English language is primarily spoken at home.

EXCLUSION CRITERIA:

  1. Serious, unstable illnesses including gastroenterologic, respiratory, cardiovascular endocrinologic, immunologic, or hematologic disease.
  2. 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).
  3. Documented history of hypersensitivity or intolerance to donepezil or other piperidine derivative.
  4. 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.

  5. Presence or history of other unstable neurological disorders such as seizure disorders,

metabolic disorders, narcolepsy or movement disorders.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01887132

Contacts
Contact: Margaret J Pekar (301) 402-1084 pekarm@mail.nih.gov
Contact: Ashura W Buckley, M.D. (301) 496-5190 shu.buckley@nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Ashura W Buckley, M.D. National Institute of Mental Health (NIMH)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )
ClinicalTrials.gov Identifier: NCT01887132     History of Changes
Other Study ID Numbers: 130164, 13-M-0164
Study First Received: June 22, 2013
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Sleep Architecture
Autism
Language Development

Additional relevant MeSH terms:
Autistic Disorder
Child Development Disorders, Pervasive
Mental Disorders Diagnosed in Childhood
Mental Disorders
Donepezil
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Nootropic Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 24, 2014