Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Controlled Trial of Intranasal Oxytocin as an Adjunct to Behavioral Therapy for Autism Spectrum Disorder
Brief Summary: This 3-year study is a trial of cognitive behavioral therapy (CBT), with or without oxytocin (OT) augmentation, in young adults with autism spectrum disorders. Participants will be randomly assigned to receive either a social skills-focused CBT intervention or a stress management/relaxation training CBT intervention. Participants will also be randomized to receive either a) intranasal oxytocin or b) a placebo drug, prior to the psychotherapy. The design of the study will enable examination of the efficacy of CBT for young adults with autism spectrum disorders. The design of the study will also allow examination of whether oxytocin enhances the efficacy of CBT.

The investigators will perform functional (fMRI) and structural (MRI) imaging with all participants prior to treatment. This will enable examination of the relations between measures of brain function and structure, and improvements in target symptoms over the course of treatment. The aim is to discover whether there are neural characteristics that can identify which participants with autism spectrum disorders are most likely to respond to CBT interventions and/or oxytocin treatment.


Options:
A: Inclusion Criteria

* Aged 6 to 17 years and weight of at least 15 kg
* Meet DSM-IV criteria for of AD, established by chart review, clinical judgment and the Autism Diagnostic Interview- Revised (ADI-R) criteria
* Clinical Global Impressions Severity (CGI-S) score of \>4 (moderately ill)
* ABC Irritability subscale score of \>18
* Mental age of at least 18 months
* If female and sexually active, must agree to an acceptable method of birth control during the trial
* Medication free or adequate washout period (2-4 weeks prior to enrollment) of psychoactive drugs (anticonvulsants permitted for seizure management if dosage is stable for 4 weeks)
* Parent/guardian able to read and provide informed consent.

Exclusion Criteria

* Psychiatric disorder that is effectively managed by psychoactive medication (e.g. ADHD, MDD)
* Prior diagnosis or evidence of genetic or other disorder that may interfere with assessments (e.g. Fragile X syndrome, Fetal alcohol syndrome, history of very low birth weight) assessed by personal and family history, dysmorphology, and clinical judgment.
* Prior use of risperidone or aripiprazole for more than 2 weeks
* Seizure during the past 6 months
* History or evidence of a medical condition that would expose them to an undue risk of a significant adverse event or interfere with assessments during the trial including but not limited to hepatic, renal, respiratory, cardiovascular, endocrine, hematologic or immunologic disease as determined by the clinical judgment of the investigator
* Current suicidal or homicidal risk
* Positive urine pregnancy test at baseline
* Dependent on other substances, with the exception of nicotine or caffeine
B: Inclusion Criteria:

* Children 5 yrs to 14 years 11 mos with clinical diagnosis of Autism, Asperger's Disorder, or PDDNOS based upon the ADI-R and clinical evaluation by DSM-IV criteria,
* Mental age equal to or greater than 24 months,
* ADHD symptoms based upon the CASI and clinical confirmed diagnosis,
* CGIS-S rating of 4 or grater for ADHD symptoms,
* A mean item score of \>1.5 on both the Parent and Teacher (non-parent caregiver) SNAP-IV 18 ADHD symptoms or the 9-symptom hyperactive-impulsive subscale (symptoms must be cross-situational),
* Reliable care provider available to bring subject to clinic visits and weekly sessions.

Exclusion Criteria:

* DSM-IV diagnosis of schizophrenia, schizoaffective disorder psychotic disorder NOS,bipolar disorder, or major depression (if accompanied by a family history of bipolar disorder) based upon evidence of suicidality, CASI, and clinical interview/history,
* Prior failed adequate trial of atomoxetine,
* Use of other psychotropic medications that produce CNS effects,
* Diagnosis of bipolar disorder, major depression, hypertension, cardiovascular disease, narrow angle glaucoma, other significant physical illness,
* Pregnancy or sexually active females (intercourse in the past 6 months, reported by either the subject or caregiver),
* Currently on effective medication treatment for ADHD,
* Prior involvement in Parent Management Training or other similar program,
* Currently on albuterol or taking beta blockers,
* Taking supplements or other complementary medical treatments where dose cannot be held at current level for duration of study
C: Inclusion Criteria:

* Age 18-40
* Able to attend in person therapy sessions in Boston
* Male
* English-speaking
* Normal or corrected vision
* No history of known genetic disorder, significant motor developmental difficulties, prematurity or brain injury
* IQ \> 90, as determined by the WASI
* Score above the cutoff on the Reciprocal Social Interactions and the Restricted, Repetitive, and Stereotyped Behaviors Domains on the ADI-R, meet criteria for PDD or autism on the ADOS, and/or meet DSM-IV criteria for Autism Spectrum Disorder according to clinician interview.

Exclusion Criteria:

* Current use of certain endocrinologically relevant medications
* Current dependence on substances other than tobacco or caffeine
* History of serious medical illness, including neurological, endocrine, cardiac, respiratory, and metabolic diseases that are counter-indications to oxytocin
* Severe, current psychiatric disorder (ie, current mania, severe depression, psychosis, suicidality, severe aggression)
* Long QT, as determined by baseline EKG
* Current participation in other psychotherapy

Additional exclusion criteria for MRI scan only:

Participants who are MRI-ineligible will be enrolled in the clinical trial portion of the study, but will not undergo the MRI scan at MIT. Exclusion criteria for MRI are:

* Presence of metal implants or other metal in the body
* History of claustrophobia or inability to tolerate MRI
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: C