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

Phase 2

Terminated

Conditions: Autism Spectrum Disorders

Interventions: Drug: Placebo
Drug: Donepezil

Registration Number: NCT01887132

Lead Sponsor: National Institute of Mental Health (NIMH)

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.

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:

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

Secondary outcome measures will be:

2. We will also measure the change in REM sleep parameters after 6, 12 and 18 months in relation to improvements in behavioral indices.

Exploratory Outcome Measures will be:

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

4. An improvement on the severity scale of the Autism Diagnostic Observation Schedule (ADOS) at 6, 12 and 18 months.

5. An improvement on the Vineland at 3, 6, 12 and 18 months

6. An exploratory analysis will investigate whether normalization of REM parameters also improves other measurements of sleep quality in children with autism.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 5

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Donepezil - Blinded	Donepezil	-
Open-Label Donepezil	Donepezil	-

Primary Outcome Measures

Name	Time	Method
Nonverbal Developmental Quotient (NVDQ)	Baseline and 12 months	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).

Secondary Outcome Measures