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

Primary Purpose

Autism Spectrum Disorders

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Donepezil

Placebo

About this trial

This is an interventional treatment trial for Autism Spectrum Disorders focused on measuring Sleep Architecture, Autism, Language Development

Eligibility Criteria

24 Months - 50 Months (Child)All SexesDoes not accept healthy volunteers

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:

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.

Sites / Locations

National Institutes of Health Clinical Center, 9000 Rockville Pike

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

Open-Label Donepezil

Donepezil - Blinded

Placebo

Arm Description

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

REM Percentage at Baseline, 6, 12 and 18 Months

REM percentage is the percentage of sleep spent in REM

Full Information

NCT ID

NCT01887132

First Posted

June 22, 2013

Last Updated

September 21, 2017

Sponsor

National Institute of Mental Health (NIMH)

1. Study Identification

Unique Protocol Identification Number

NCT01887132

Brief Title

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

Official Title

A Randomized Controlled Trial of Donepezil for REM Enhancement and Behavioral Change in Autism

Study Type

Interventional

2. Study Status

Record Verification Date

September 2017

Overall Recruitment Status

Terminated

Study Start Date

June 2013 (undefined)

Primary Completion Date

December 2015 (Actual)

Study Completion Date

December 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Institute of Mental Health (NIMH)

4. Oversight

5. Study Description

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: 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: 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: An improvement in the Expressive Language and the Receptive Language subscales of the Mullen Scales at 18 months. An improvement on the severity scale of the Autism Diagnostic Observation Schedule (ADOS) at 6, 12 and 18 months. An improvement on the Vineland at 3, 6, 12 and 18 months An exploratory analysis will investigate whether normalization of REM parameters also improves other measurements of sleep quality in children with autism.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Autism Spectrum Disorders

Keywords

Sleep Architecture, Autism, Language Development

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

Double

Allocation

Randomized

Enrollment

5 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Open-Label Donepezil

Arm Type

Experimental

Arm Title

Donepezil - Blinded

Arm Type

Experimental

Arm Title

Placebo

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

Donepezil

Intervention Type

Drug

Intervention Name(s)

Placebo

Primary Outcome Measure Information:

Title

Nonverbal Developmental Quotient (NVDQ)

Description

Time Frame

Baseline and 12 months

Secondary Outcome Measure Information:

Title

REM Percentage at Baseline, 6, 12 and 18 Months

Description

REM percentage is the percentage of sleep spent in REM

Time Frame

Baseline, 6, 12 and 18 months

Other Pre-specified Outcome Measures:

Title

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

Title

Mullen Scales at 18 Months

Time Frame

18 months

Title

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

Time Frame

6, 12 and 18 months

Title

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

Time Frame

3, 6, 12 and 18 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

24 Months

Maximum Age & Unit of Time

50 Months

Accepts Healthy Volunteers

Eligibility Criteria

INCLUSION CRITERIA: 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. 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: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ashura W Buckley, M.D.

Organizational Affiliation

National Institute of Mental Health (NIMH)

Official's Role

Principal Investigator

Facility Information:

Facility Name

National Institutes of Health Clinical Center, 9000 Rockville Pike

City

Bethesda

State/Province

Maryland

ZIP/Postal Code

20892

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

IPD shared via NIMH repository protocol.

Citations:

PubMed Identifier

17663613

Citation

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.

Results Reference

background

PubMed Identifier

19521762

Citation

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.

Results Reference

background

PubMed Identifier

8272449

Citation

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.

Results Reference

background

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

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