Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized Controlled Trial of Donepezil for REM Enhancement and Behavioral Change in Autism
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.


Options:
A: Inclusion Criteria:

1. Males and females, Aged between 3 and 12 years.
2. Autistic disorder - DSM-IV criteria.
3. A score of at least moderately impaired on the CGI-Severity item.
4. Clinical judgment that medication treatment for autism is indicated.

Exclusion Criteria:

1. Rett's disorder, childhood disintegrative disorder, Asperger's disorder, and PDD, NOS.
2. Psychotic disorder (DSM-IV) (including schizophreniform disorder and schizophrenia).
3. Major depressive disorder (DSM-IV).
4. Bipolar disorder (DSM-IV).
5. History of psychoactive drug in the previous 2 weeks prior to phase 1.
6. A history of treatment with olanzapine for a cumulative period of greater than 2 weeks prior to entering phase 1.
7. Systemic diseases such as cardiac, renal, thyroid diseases, uncontrolled seizure disorder (seizure disorder that is not controlled by anti-epileptic medication - a child who is seizure free for a period of 6 months on a stable dose of antiepileptic drug would be considered controlled), or diabetes mellitus.
8. Children with a known medical cause for autistic disorder.
9. Abnormal fasting blood glucose or history of diabetes.
10. Baseline body mass index (BMI) greater than the 90th percentile for age and gender (CDC growth charts, Kuczmarski et al, 2000) (because of risk of weight gain).
11. Baseline QTc \>450 msec. Note: Historically, patients we evaluate do not have QTc values \>450.
12. Dyskinesias at baseline (per the criteria of Schooler and Kane, 1982).
B: Inclusion Criteria:

1. Completed at least 12 weeks of exposure to study drug in lead-in study MEM-MD-91 (NCT01592786)
2. Met responder criterion at two consecutive visits separated by at least two weeks in lead-in study MEM-MD-91
3. Provide written informed assent, when developmentally appropriate, to participate in the study before conduct of any study-specific procedures. The parent/guardian/LAR must provide written informed consent before the patient's participation in the study. A separate written informed consent for the caregiver must also be obtained before the conduct of any study specific procedures
4. Have a knowledgeable caregiver who is capable of providing reliable information about the patient's condition, attending all clinic visits with the patient, and overseeing the administration of study drug. Every effort should be made to maintain the same caregiver as used in the lead-in study throughout this study
5. Have normal results from the physical examination, laboratory tests, ECG, and vital signs at Visit 1 of this study (last visit of Study MEM-MD-91). Any abnormal findings must be deemed not clinically significant by the Investigator and documented
6. Be able to speak and understand English sufficiently (or their native language if this can be accommodated by the site), as well as have a caregiver and parent/guardian/LAR who is able to speak and understand English sufficiently (or their native language if this can be accommodated by the site), to comprehend the nature of the study and to allow for the completion of all study assessments
7. Have a family that is sufficiently organized and stable to guarantee adequate safety monitoring and continuous attendance to clinic visits for the duration of the study
8. Females who are 9 years and older or who have had onset of menses must have a negative urine pregnancy test at Visit 1
9. Age of 6 years to 12 years at the time of entry into lead in study MEM-MD-91

Exclusion Criteria:

1. Patients with a concurrent medical condition that might interfere with the conduct of the study, confound interpretation of the study results, or endanger the patient's well being
2. Significant risk of suicidality based on the Investigator's judgment, the Aberrant Behavior Checklist-Irritability subscale (ABC-I), or if appropriate, as indicated by a response of "yes" to questions 4 or 5 in the suicidal ideation section of the Children's C-SSRS (Columbia-Suicide Severity Rating Scale) or any suicidal behavior.
3. Patients with evidence or history of malignancy (other than excised basal cell carcinoma) or any significant hematologic, endocrine, cardiovascular (including any rhythm disorder), neurologic, respiratory, renal, hepatic, or gastrointestinal disease
4. Female patients of child-bearing potential who are not using or not willing to use a conventional method of contraception approved by the PI. Abstinence is an acceptable method of contraception
5. Patients requiring treatment with prohibited concomitant medications
6. Patients who, in the opinion of the Investigator, might not be suitable for the study
7. Employee or immediate relative of an employee of Forest Laboratories, Inc., any of its affiliates or partners, or the study center
C: * 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:

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.
D: Inclusion Criteria:

* Able to walk
* Diagnosis of Autistic Disorder, Asperger's Disorder, or PDD-NOS
* Have a score greater than or equal to (\>) 8 on the sum of items 1A, 2, 3 and 5 of the Compulsions Subscale of the Revised CYBOCS.
* Have a rating of at least moderate behavioral disturbance based on the modified Clinical Global Impression-Severity of Illness score (CGI-S) at the time of screening (See description below).
* Be free of psychotropic medication for at least one month for fluoxetine, two weeks for other SSRIs and neuroleptics, and for 5 days for stimulants prior to baseline ratings.
* Be judged reliable for medication compliance and agree to keep appointments for study contacts and tests as outlined in the protocol (both subject and guardian(s)).

Exclusion Criteria:

* Medical contraindications to therapy with SSRIs
* Prior exposure to citalopram (or escitalopram) of sufficient dose or duration to determine response status
* History of treatment failure to a clinically adequate trial of two select SSRIs
* Diagnosis of Rett's Disorder or Childhood Disintegrative Disorder
* Uncontrolled epilepsy, with a seizure within past 6 months
* Child weighs less than (\<) 15 kg at screening contact.
* Pregnancy
* Presence of chronic medical conditions that might interfere with study participation or where study participation would be contraindicated
* Clinically significant abnormal baseline laboratory testing
* History of bipolar disorder or manic episode induced by antidepressant exposure
* Documented need for ongoing psychotropic medications besides study medication (with the exception of stable dose (at least 3 month) anti-convulsants for seizures).
* Concomitant medication that would interfere with participation in the study.
* Recent (\< 2 months) initiation of behavior therapy (such as parent training, applied behavior analysis or behavior modification) in a clinic, with a private practitioner or in a school program. Participants who are in an established behavior therapy program (defined as greater than (\>) 2 months for clinic or private practitioner or greater than (\>) 1 month for school program) can be included in the study. Families will be asked not to initiate any new behavior therapy during the study.

Answer: C