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TerminatedNCT01887132Updated Sep 25, 2017Results posted

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

A Phase 2 interventional study of Donepezil and Placebo in Autism Spectrum Disorders, sponsored by National Institute of Mental Health (NIMH). Terminated at 1 site in United States. Open to participants aged 24 Months to 50 Months. Per ClinicalTrials.gov, last updated 2017-09-25.

Sponsored by National Institute of Mental Health (NIMH) · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
5
Allocation
Randomized
Ages
24 Months to 50 Months
Sex
All
01

Study 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.
Read the 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.
02

Conditions studied

  • Autism Spectrum Disorders

Keywords

  • Sleep Architecture
  • Autism
  • Language Development
03

In context

Autistic Disorder

1,344 studies on the registry are indexed under Autistic Disorder; 334 are open to participants now.

This study's enrollment of 5 is below the median of 45 across 1,044 interventional studies indexed under Autistic Disorder.

Browse Autistic Disorder studies →

Lead sponsor

National Institute of Mental Health (NIMH) is the lead sponsor of 359 studies on the registry; 46 are open to participants now.

Of its 25 completed or terminated interventional studies of FDA-regulated products, 24 (96%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
24 Months to 50 Months
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Diagnosis of an Autism Spectrum Disorder (DSM-IV diagnoses of autistic disorder or Pervasive Developmental Disorder, Not Otherwise Specified).

    1. Male or Female subjects between the ages of 24 and 50 months.
    2. Language scores (from the Mullen Scales of Early Learning) that are at least 1.5 SD lower than the mean.
    1. 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.
    1. 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.
    1. Demonstrated REM% two standard deviations or more below the normative values for age for the randomized controlled trial part.
    1. English language is primarily spoken at home.

Exclusion criteria

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.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double
Enrollment
5 participants (actual)

Study arms

  • Experimental
    Open-Label Donepezil

    Drug: Donepezil

  • Experimental
    Donepezil - Blinded

    Drug: Donepezil

  • Placebo comparator
    Placebo

    Drug: Placebo

Interventions

  • DrugDonepezil
  • DrugPlacebo
06

What researchers measure

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).

    Time frame: Baseline and 12 months

Secondary outcomes

  1. REM Percentage at Baseline, 6, 12 and 18 Months

    REM percentage is the percentage of sleep spent in REM

    Time frame: Baseline, 6, 12 and 18 months

Other outcomes

  1. 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

  2. Mullen Scales at 18 Months

    Time frame: 18 months

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

    Time frame: 6, 12 and 18 months

  4. Vineland Parent Questionnaire at 3, 6, 12 and 18 Months

    Time frame: 3, 6, 12 and 18 months

07

Results

Posted Sep 25, 2017
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.

Participant flow

Participant flow — Overall Study
MilestoneOpen-Label Donepezil
Started4
Completed4
Not completed0

Outcome measures

PrimaryNonverbal 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).

Time frame:
Baseline and 12 months
Reported as:
Number · units on a scale
Nonverbal Developmental Quotient (NVDQ)
units on a scaleOpen-Label Donepezil
NVDQ for participant 1 at Baseline51.61
NVDQ for participant 2 at Baseline48.89
NVDQ for participant 3 at Baseline58.97
NVDQ for participant 4 at Baseline54.88
NVDQ for participant 1 at 12 mos52.38
NVDQ for participant 2 at 12 mos44.74
NVDQ for participant 3 at 12 mos54.00
NVDQ for participant 4 at 12 mos45.45
SecondaryREM Percentage at Baseline, 6, 12 and 18 Months

REM percentage is the percentage of sleep spent in REM

Time frame:
Baseline, 6, 12 and 18 months
Reported as:
Number · percentage of sleep
REM Percentage at Baseline, 6, 12 and 18 Months
percentage of sleepOpen-Label Donepezil
REM percentage, participant 1, Baseline17.2
REM percentage, participant 2, Baseline18.6
REM percentage, participant 3, Baseline19.9
REM percentage, participant 4, Baseline12.1
REM percentage, participant 1, 6 mos27.5
REM percentage, participant 2, 6 mos18.8
REM percentage, participant 3, 6 mos9.7
REM percentage, participant 4, 6 mos18.9
REM percentage, participant 1, 12 mos18.2
REM percentage, participant 2, 12 mos10.1
REM percentage, participant 3, 12 mos27.5
REM percentage, participant 4, 12 mos8.5
REM percentage, participant 1, 18 mos27.8
REM percentage, participant 2, 18 mos6
REM percentage, participant 3, 18 mos19.8
REM percentage, participant 4, 18 mos11.6
Other pre-specifiedAn Exploratory Analysis Will Investigate Whether Normalization of REM Parameters Also Improves Other Measurements of Sleep Quality in Children With Autism.
Time frame:
12 months

Results for this outcome have not been posted.

Other pre-specifiedMullen Scales at 18 Months
Time frame:
18 months

Results for this outcome have not been posted.

Other pre-specifiedAutism Diagnostic Observation Schedule (ADOS) at 6, 12 and 18 Months
Time frame:
6, 12 and 18 months

Results for this outcome have not been posted.

Other pre-specifiedVineland Parent Questionnaire at 3, 6, 12 and 18 Months
Time frame:
3, 6, 12 and 18 months

Results for this outcome have not been posted.

Adverse events

Collected over Baseline to 18 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Open-Label Donepezil0/4 (0%)0/4 (0%)0/4 (0%)

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Open-Label Donepezil
<=18 years4
Between 18 and 65 years0
>=65 years0
Age, Continuous
Age, Continuous(years)Open-Label Donepezil
Mean3.2 (2.1 to 3.9)
Sex: Female, Male
Sex: Female, Male(Participants)Open-Label Donepezil
Female0
Male4
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Open-Label Donepezil
Hispanic or Latino0
Not Hispanic or Latino4
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Open-Label Donepezil
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American1
White3
More than one race0
Unknown or Not Reported0
Region of Enrollment
Region of Enrollment(participants)Open-Label Donepezil
United States4
08

Study locations

1 site
  • National Institutes of Health Clinical Center, 9000 Rockville Pike
    Bethesda, Maryland 20892, United States
09

References and documents

Publications

  • 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. PubMed 17663613 ↗
  • 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. PubMed 19521762 ↗
  • 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. PubMed 8272449 ↗

Individual participant data

Plan to share: Yes — IPD shared via NIMH repository protocol.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 25, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01887132
Lead sponsor
National Institute of Mental Health (NIMH)
Responsible party
Sponsor
First posted
Jun 26, 2013
Start date
Jun 2013
Primary completion
Dec 2015
Completion
Dec 2015
Results posted
Sep 25, 2017
Last update
Sep 25, 2017

Study contacts

Ashura W Buckley, M.D.
principal investigator · National Institute of Mental Health (NIMH)
View the source record on ClinicalTrials.gov ↗

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