A Trial of the Drug Donepezil for Sleep Enhancement and Behavioral Change in Children With Autism
Condition: Autism Spectrum Disorders
MeSH terms: Autistic Disorder; Autism Spectrum Disorder
Intervention: Donepezil; Placebo
Intervention MeSH terms: Donepezil
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 5.0
Sex: All
Minimum age: 24 Months
Maximum age: 50 Months
Healthy volunteers: No
Keywords: Sleep Architecture; Autism; Language Development

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.
    

Eligibility 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.