Autism Spectrum DisordersPhase 2NCT01887132
A Trial of the Drug Donepezil for Sleep Enhancement and Behavioral Change in Children With Autism
A Phase 2 study testing Donepezil in people with Autism Spectrum Disorders, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 24 to 50 months
- Conditions the study is for
- Autism Spectrum Disorders
- What is being tested?
- Donepezil
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2013to Dec 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 24 to 50 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: A Randomized Controlled Trial of Donepezil for REM Enhancement and Behavioral Change in Autism
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.
Read more
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
- 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.
- Conditions
- Autism Spectrum Disorders
- Being tested
- Donepezil, Placebo
- Keywords
- Sleep Architecture, Autism, Language Development
- Medical subject headings
- Autism Spectrum Disorder, Autistic Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DonepezilDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Open-Label Donepezil | Experimental | Not described Receives: Drug: Donepezil |
| Donepezil - Blinded | Experimental | Not described Receives: Drug: Donepezil |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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
Measured: Baseline, 6, 12 and 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2013 (estimated)
- Study startJun 2013
- Primary completionDec 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Autism Spectrum DisordersStudies of the same condition, open and under way.
- More trials run by National Institute of Mental Health (NIMH)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Ashura W Buckley, M.D., Principal investigator, National Institute of Mental Health (NIMH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01887132
- Sponsor's protocol ID
- 130164
- Other IDs
- 13-M-0164
- Status last verified
- Sep 2017
- First submitted
- 22 Jun 2013
- Last updated
- 25 Sep 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Individual data sharing
- Yes: IPD shared via NIMH repository protocol.
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 17663613Anderson 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 19521762Bliwise 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 8272449Ure A, Cox GR, Haslam R, Williams K. Acetylcholinesterase inhibitors for autistic spectrum disorders. Cochrane Database Syst Rev. 2023 Jun 1;6(6):CD013851. doi: 10.1002/14651858.CD013851.pub2.
PubMed 37267443
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Trial of Donepezil for REM Enhancement and Behavioral Change in Autism
- ClinicalTrials.gov ID
- NCT01887132
- Acronym / sponsor ID
- 130164
- Conditions
- Autism Spectrum Disorders
- Keywords
- Sleep Architecture, Autism, Language Development
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 5 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- Jun 2013
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 26 Jun 2013 (estimated)
- Results
- Posted 25 Sep 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Open-Label Donepezil | Experimental | Drug: Donepezil |
| Donepezil - Blinded | Experimental | Drug: Donepezil |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 24 to 50 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Donepezil | Drug | Donepezil - Blinded, Open-Label Donepezil |
| Placebo | Drug | Placebo |
Primary outcome
Nonverbal Developmental Quotient (NVDQ)
Time frame: 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).
1 secondary outcome
REM Percentage at Baseline, 6, 12 and 18 Months
Time frame: Baseline, 6, 12 and 18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 17663613Anderson 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.
- Background: PubMed 19521762Anderson 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.
- Background: PubMed 8272449Bliwise 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.
- Derived from this study: PubMed 37267443Ure A, Cox GR, Haslam R, Williams K. Acetylcholinesterase inhibitors for autistic spectrum disorders. Cochrane Database Syst Rev. 2023 Jun 1;6(6):CD013851. doi: 10.1002/14651858.CD013851.pub2.
- Individual participant dataSharing planned: Yes. IPD shared via NIMH repository protocol.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ashura W Buckley, M.D. principal investigator
National Institute of Mental Health (NIMH)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Donepezil in people with Autism Spectrum Disorders, run by National Institute of Mental Health (NIMH) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Sep 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Nonverbal Developmental Quotient (NVDQ) (time frame: Baseline and 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01887132, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2017.