Please select the eligibility criteria that correspond to the clinical trial below.
Title: Double-blind , Randomized, Placebo Controlled Study of N-Acetyl Cysteine in Autism.
Brief Summary: The purpose of the study is to test the tolerability and efficacy of N-Acetyl Cysteine (NAC) in children with Autism. NAC is a compound that increases the levels of Glutathione, the body's main antioxidant. Glutathione is a compound in the blood that is part of a natural defense system (the antioxidant system). Anti-oxidants protect the body from damage caused by internal toxins called "free radicals." It is possible that children with Autism tend to have lower levels of glutathione, an important compound in our bodies that helps combat the effects of toxic free radicals.

We hope that by studying the antioxidant system in more detail, we will increase our understanding of the reasons why people develop Autism so that we can design better ways to treat individuals with this condition. This study is meant to test the safety tolerability of NAC and its effectiveness in the treatment of behavioral difficulties in children with autism. It will also examine the possible benefit of this agent in improving the core deficits in autism such as social deficits.


Options:
A: Inclusion Criteria:

1. Outpatients between 3.0 and 12.11 years of age inclusive
2. Males and females who are physically healthy
3. diagnosis of autism based Diagnostic and Statistical Manual (DSM-IV-TR) criteria, the Autism Diagnostic Interview-Revised, and expert clinical evaluation
4. Clinical Global Impression Severity rating of 4
5. Care provider who can reliably bring subject to clinic visits, can provide trustworthy ratings, and interacts with subject on a regular basis
6. Ability of subject to swallow the compound
7. Stable concomitant medications for at least 2 weeks
8. No planned changes in psychosocial interventions during the open-label N-Acetyl Cysteine trial

Exclusion Criteria:

1. DSM-IV-TR diagnosis of schizophrenia, schizoaffective disorder, or psychotic disorder not otherwise specified
2. Prior adequate trial of N-Acetyl Cysteine
3. Active medical problems: unstable seizures, significant physical illness (e.g., serious liver or renal pathology)
4. Pregnancy or sexually active females
5. Subjects taking antioxidant agents and glutathione prodrugs will be excluded from the study except if they have been off these compounds for at least 4 weeks
B: 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.
C: Inclusion Criteria:

* Autistic Disorder, Asperger's Disorder, or Pervasive Developmental Disorder not otherwise specified
* Weight \> 30 lbs
* IQ \>= 35 or mental age of at least 18 months

Exclusion Criteria:

* Psychotic Disorder
* History of intolerance or nonresponse to risperidone
* Pregnancy
* History of neuroleptic malignant syndrome
D: Inclusion Criteria:

Autism/ADHD Group:

* DSM-IV diagnosis of autistic disorder, as per the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS)
* Child manifests current symptoms of ADHD

Autism/non-ADHD Group:

* Meets the diagnostic criteria for autism, as above, but does not meet the diagnostic criteria for ADHD

Exclusion Criteria:

In both groups, exclusion criteria will include:

* Sensory or motor deficits sufficient to interfere with testing (e.g., blindness, severe cerebral palsy)
* Serious neurological disorders (e.g., epilepsy, stroke)
* Down syndrome, fragile X syndrome, Tourette syndrome, or fetal alcohol syndrome
* Bipolar disorder or a family history of bipolar disorder in a first-degree relative
* Other serious psychopathology that resulted in psychiatric hospitalization (e.g., for psychotic episode). The investigators will screen for this using the Diagnostic Interview for Children and Adolescents (DICA)-IV, and getting a complete developmental/medical history
* Serious physical handicaps that would interfere with performance on laboratory tasks
* IQ less than 50 and greater than 130
* Verbal mental age (VMA) less than 36 months (to exclude participants unable to understand simple task instructions)

In the autism/ADHD group, further exclusion criteria apply to the MPH trial:

* History of intolerance to MPH
* Weight less than 20 kg or greater than 59 kg (less than 44 pounds or greater than 130 pounds)
* Concomitant use of dextroamphetamine preparations (Dexedrine, Dextrostat), mixed amphetamine salts (Adderall XR), other MPH preparations (e.g., Concerta, Metadate); venlafaxine, bupropion, atomoxetine, guanfacine, modafinil.
* Concomitant use of any herbal preparations
* Medical condition for which stimulants are contraindicated (e.g., high blood pressure)
* Past treatment failure on a methylphenidate trial

Answer: A