The Effect of Donepezil (Aricept(Registered Trademark)) on REM Sleep in Children With Autism

NCT00695136 | Completed Phase 1 Results

• 2 other identifiers: 08015408-M-0154
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This study will test whether donepezil (Aricept(Registered Trademark)), a drug that is approved by the Food and Drug Administration to treat Alzheimer's disease, can increase rapid eye movement (REM) sleep in children with autism and autism spectrum disorder (ASD). Some children with autism and ASD spend very little time in REM sleep. In some studies, decreased REM sleep has been associated with learning and behavior problems. Donepezil can increase REM sleep in some adults with different disorders. If it can increase REM sleep in children in this study, it might be able to be used in future studies to see if it can help learning and behavior problems in children with autism and ASD. Children between 2 and 10 years of age with autism or an ASD whose percentage of REM sleep time is well below the average for children of the same age may be eligible for this study. Candidates are screened with a medical history, physical and neurological examinations, blood tests, electroencephalogram (EEG) and a sleep study. The sleep study requires an overnight stay at the NIH Clinical Center in which the child is monitored with electrodes for EEG and heartbeat recording, a tube taped below the nose to measure airflow, a probe on a finger to record oxygen levels and a small watch-like machine on the wrist to record movements. Participating children may be required to have up to six overnight stays for sleep studies at the Clinical Center. The children start by taking 1.25 mg of donepezil for 2 to 4 weeks. Then they are admitted to the NIH Clinical Center for a sleep study, blood tests and EKG. Those whose REM sleep increases to normal levels stay on 1.25 mg of donepezil for 8 more weeks, after which they are admitted to the Clinical Center for a final physical examination, blood draw and sleep study. That ends their participation in the study. Children whose REM sleep does not increase to normal on 1.25 mg of donepezil are given a higher dose (2.5 mg) for 2 to 4 weeks, and the above procedure is repeated. Those whose REM sleep does not increase to normal on 2.5 mg of donepezil take 5 mg of the drug for 2 to 4 weeks, and the above procedure is repeated once more. Children whose REM sleep does not increase to normal on 5 mg of donepezil stop the medication and end their participation in the study. At each study visit, study researchers talk to the parents and examine the children to determine if donepezil is affecting the child's behavior and if the child is hav...

Conditions

Autism; Cognition Disorder

Keywords

Autism; Cognitive Disorder; Sleep; Autism Spectrum Disorder; ASD

Outcome Measures

Primary Outcomes (1)

• Change in Percentage of Time That Subjects With Autism Spend in REM Sleep.

  1 month (from baseline to 1.25 mg dose)

Study Arms (1)

Open label single arm

EXPERIMENTAL

Single group study of Donepezil

Drug: Donepezil hydrochloride; Behavioral: Increase REM sleep percentage

Interventions

Donepezil hydrochloride DRUG

Open label single arm

Increase REM sleep percentage BEHAVIORAL

Open label single arm

Eligibility Criteria

• Age: 2 Years - 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Diagnosis of autism spectrum disorder
• Male or female subjects, ages 2 through 10 years.
• 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.
• 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.

You may not qualify if:

• 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 that is contraindicated for co-administration with donepezil.
• Presence or history of neurological disorders, including seizure disorders.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• McGrath MJ, Cohen DB. REM sleep facilitation of adaptive waking behavior: a review of the literature. Psychol Bull. 1978 Jan;85(1):24-57. No abstract available.

  PMID: 203966 BACKGROUND

• Mirmiran M, van den Dungen H, Uylings HB. Sleep patterns during rearing under different environmental conditions in juvenile rats. Brain Res. 1982 Feb 11;233(2):287-98. doi: 10.1016/0006-8993(82)91203-3.

  PMID: 7059812 BACKGROUND

• Guzman-Marin R, Ying Z, Suntsova N, Methippara M, Bashir T, Szymusiak R, Gomez-Pinilla F, McGinty D. Suppression of hippocampal plasticity-related gene expression by sleep deprivation in rats. J Physiol. 2006 Sep 15;575(Pt 3):807-19. doi: 10.1113/jphysiol.2006.115287. Epub 2006 Jul 6.

  PMID: 16825295 BACKGROUND

MeSH Terms

Conditions

Autistic Disorder; Cognition Disorders; Cognitive Dysfunction; Autism Spectrum Disorder

Interventions

Donepezil

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; Neurocognitive Disorders

Intervention Hierarchy (Ancestors)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds

Limitations and Caveats

No controls and small number of patients.

Results Point of Contact

• Title: Susan E. Swedo, MD
• Organization: Pediatrics & Developmental Neuroscience Branch, NIMH

swedos@mail.nih.gov

301-496-5323

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief, Pediatrics & Developmental Neuroscience Branch, NIMH

Study Record Dates

• First Submitted: June 10, 2008
• First Posted: June 11, 2008
• Study Start: June 1, 2008
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: April 24, 2013
• Results First Posted: April 24, 2013

Record last verified: 2013-04

Locations

US (1)