Please select the eligibility criteria that correspond to the clinical trial below.
Title: Divalproex Sodium vs. Placebo in Childhood/Adolescent Autism
Brief Summary: The study is designed to assess the efficacy of treatment with divalproex sodium (DS) vs. placebo in childhood/adolescent autism fulfilling DSM-IV and Autism Diagnostic Interview (ADI) criteria. Currently, there are no FDA-approved treatments for this disorder, although behavioral and educational therapies and a variety of medications may play a role in the management of some autistic symptoms.


Options:
A: 1. Meets DSM-IV, ADI-R and ADOS-G criteria for autistic disorder
2. Age 5-17 years
3. Outpatients
4. Parent or legal guardian willing to sign informed consent.
5. Male or female patients
6. Patient scores at least a "4" (moderately ill) on the Clinical Global Impression Scale for Autistic Disorder (CGI AD).
7. Children who are minimally or non- verbal as indicated by a score of 50% of an 18 month old on the MacArthur Communicative Development Inventory

Exclusion Criteria:

1. Subjects with any of the following past or present mental disorders: psychotic disorders, mood disorders, including bipolar disorders.
2. Subjects who have displayed significant self-injurious behavior (children who have caused visible harm to themselves).
3. Subjects with active seizure disorder (seizures within the past six months).
4. Subjects with clinically significant or unstable medical illness, including patients with current evidence of clinically significant hematopoietic, or cardiovascular disease.
5. Subjects with present or history of the following:

   * gastrointestinal, liver, kidney, or other known conditions which will presently interfere with the absorption, distribution, metabolism, or excretion of drugs,
   * seizure disorders (active), cerebrovascular disease or brain trauma as etiology of autistic behavior,
   * clinically significant unstable endocrine disorder, such as hypo- or hyperthyroidism or diabetes,
   * recent history or presence of any form of malignancy.
6. Subjects who report significant improvement of autism symptoms and behaviors to current medications or have only global autism ratings on the CGI of absent, minimal or mild severity, or who are more than minimally verbal.
7. Subjects whose global autism ratings are assessed as being absent, minimal or mild.
8. Treatment within the previous 30 days with any drug known to have a well-defined potential for toxicity to a major organ.
9. Subjects with clinically significant abnormalities in laboratory tests or physical exam.
10. Subjects likely to require any other psychotropic medication during the study, with the exception of clonidine for insomnia (started at least one month prior to entrance into the study), as well as anticonvulsants at a constant dose for stable seizure disorder or, unless otherwise permitted.
11. Subjects unable to tolerate taper from psychoactive medication, if specified.
12. Subjects with a history of hypersensitivity or severe side effects associated with the use of galantamine, or other acetylcholinesterase inhibitors.
13. Subjects with a history of prior treatment with galantamine of 4mg/day for 6 weeks.
14. Subjects who have received any of the following interventions within the prescribed period before starting treatment:

    * investigational drugs within the previous 30 days.
    * monoamine oxidase inhibitors within the previous fourteen days.
    * long-acting phenothiazines within the previous six weeks.
    * other psychotropic drugs within the previous seven days, unless otherwise permitted.
15. Subjects with any organic or systemic disease or patients who require a therapeutic intervention, not otherwise specified, which would confound the evaluation of the safety of the study medication.
16. Subjects who reside in a remote geographical area or who do not have regular access to transportation to the clinical facility.

Gender
B: Inclusion Criteria:

* Clinical diagnosis of Autism Spectrum Disorder, Asperger Syndrome or Autism
* Male
* Age between 18 and 40 years old

Exclusion Criteria:

* Associated neuro(psycho)logical disorder (i.e. epilepsy, concussion, stroke)
* Eye sight worse than + or - 7
* Genetic syndrome
* Color blindness
* Any contraindication to neuroimaging research as assessed with the MRI screening list:

MRI contraindications:

pacemaker, implanted defibrillator, ear implant / a cochlear implant, insulin or implanted pump, a neurostimulator or VP shunt, any metallic object in the eyes (metallic fragments)
C: 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).
D: Meets DSM-IV, ADI, and ADOS criteria for autistic disorder

Age 5-17.

Outpatients

Parent/legal guardian signing informed consent, and assent documented for patient with demonstrated capacity to provide it.

Sexually active females of childbearing potential must use an acceptable method of birth control (oral contraceptive medications \[the administration of which must be supervised by a parent or guardian\], IUD, depot medication or tubal ligation) and have a negative serum pregnancy test prior to entry into the study.

Subject scores at least "4" (moderately ill) on the Clinical Global Impression-Severity Scale for Autistic Disorder (CGI-AD).

Subject meets the following criteria at pre-study diagnostic assessment and baseline assessment: OAS-M 13 or ABC-Irritability Subscale 18 (raw scores).

Subjects with history of seizures, who have been seizure-free for 6 months on a stable dose of anticonvulsant medication other than divalproex sodium or related formulations (e.g., depakene). Non-medicated subjects with a history of seizures who have been seizure-free for 6 months. Subjects with abnormal EEG but no clinical seizures.

State exclusion criteria for enrollment in study:

Subjects who are pregnant or nursing mothers. Sexually active women of childbearing potential who are not using adequate birth control measures (detailed above in inclusion criteria).

Subjects with overall adaptive behavior scores below the age of two years on the Vineland Adaptive Behavior Rating Scale.

Subjects with active or unstable epilepsy.

Subjects with any of the following past or present mental disorders: schizophrenia, schizoaffective disorder or organic mental disorders.

Subjects who are a serious suicidal risk.

Subjects with clinically significant or unstable medical illness that would contraindicate participation in the study, including hematopoietic or cardiovascular disease, pancreatitis, liver toxicity, and polycystic ovary syndrome.

Subjects reporting history of encephalitis, phenylketonuria, tuberous sclerosis, fragile X syndrome, anoxia during birth, pica, neurofibromatosis, hypomelanosis of Ito, hypothyroidism, Duchenne muscular dystrophy, and maternal rubella.

Patients with history of the following:

gastrointestinal, liver, or kidney, or other known conditions which will presently interfere presently with the absorption, distribution, metabolism, or excretion of drugs; cerebrovascular disease or brain trauma; clinically significant unstable endocrine disorder, such as hypo- or hyperthyroidism; recent history or presence of any form of malignancy

Treatment within the previous 30 days with any drug known to a well-defined potential for toxicity to a major organ

Subjects with clinically significant abnormalities in laboratory tests or physical exam.

Subjects likely to require ECT or any other psychotropic medication during the study, unless otherwise permitted.

Subjects unable to tolerate taper from psychoactive medication if necessary.

Subjects with a history of hypersensitivity or severe side effects associated with the use of divalproex sodium, or other an ineffective prior therapeutic trial of divalproex sodium (serum levels within range of 50-100 ug/ml for 6 weeks).

Subjects who have received any of the following interventions within the prescribed period before starting treatment:

investigational drugs within the previous 30 days; depot neuroleptic medication; psychotropic drugs not permitted for concurrent use in the study within the previous seven days; fluoxetine within the previous five weeks.

Subjects who have begun any new alternative non-medication treatments, such as diet, vitamins, and psychosocial therapy, within the previous three months.

Subjects with any organic or systemic disease or patients who require a therapeutic intervention, not otherwise specified, which would confound the evaluation of the safety of the study medication.

Subjects who reside in a remote geographical area who do not have regular access to transportation to the clinical facility.

Answer: D