Please select the eligibility criteria that correspond to the clinical trial below.
Title: Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism
Brief Summary: We propose a study which will combine multiple modalities in evaluating the treatment response of children with autism spectrum disorders (ASD) to acetyl-choline esterase (AChE) inhibitors and choline supplements. The primary objective of the study is to examine the efficacy of this treatment in improving core autistic symptoms. The Secondary objective of the study is to evaluate the safety and tolerability of the treatment protocol in ASD children. Exploratory objectives include evaluation of the influence of the treatment on linguistic performance, comorbid behaviors, adaptive functioning and executive functions.


Options:
A: Inclusion Criteria:

1. Outpatients 5-17 years of age inclusive.
2. Meet Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). DSM-5 criteria will be established by a clinician with expertise with individuals with ASD. Diagnosis will be supported by the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2).
3. Complex language to qualify for ADOS-2 modules 3 or 4.
4. If already receiving stable concomitant medications affecting behaviour, have stable regimens with no changes during the preceding 6 weeks prior to Screening, and will not electively initiate new or modify ongoing medications for the duration of the study.
5. If already receiving stable non-pharmacological educational and behavioural interventions, have continuous participation during the preceding 3 months prior to Screening, and will not electively initiate new or modify ongoing interventions for the duration of the study.
6. Have normal physical examination and laboratory test results at Screening. If abnormal, the finding(s) must be deemed clinically insignificant by the Investigator.
7. Ability to obtain written informed consent from the participant, if developmentally appropriate. If a participant does not have the capacity to consent, ability to obtain assent (if developmentally appropriate), as well as written informed consent from their parent(s)/legal guardian(s).

Exclusion Criteria:

1. Pregnant females; sexually active females on inadequate birth control.
2. Have a serious medical condition that, based on Investigator judgment, might interfere with the conduct of the study, confound interpretation of the study results, or endanger their own well-being. Have evidence of any significant hematological, endocrine, cardiovascular (including uncorrected symptomatic congenital heart disease), respiratory, renal, hepatic, or gastrointestinal disease, not including mild common pediatric diseases in these areas that are stable (e.g. mild asthma, constipation, etc.).
3. Have unstable epilepsy (i.e. seizures occurring within the last 6 months), or have epilepsy and not on stable doses of antiepileptic medications (i.e. dose changes within the last 3 months).
4. Have a history of drug abuse.
5. Have hypersensitivity to arbaclofen or any components of its formulation.
6. Unable to tolerate venipuncture procedures for blood sampling.
7. Actively enrolled in another intervention study.
8. Taking racemic bacblofen, vigabatrin, tiagapine, riluzole, clobazam or regular benzodiazepine use (prn and hs use is allowed).
9. Unable to take oral medications.
10. Known hypersensitivity to racemic baclofen.
11. Inability to speak and understand English sufficiently enough to allow for the completion of all study assessments (parent/legal guardian; participant).
B: Inclusion criteria:

* A formal diagnosis of Autism or Pervasive Developmental Disorder not otherwise specified (PDD-NOS), given by a child neurologist.
* Age: 10-18 years.
* A signed parental consent form.

Exclusion criteria:

* Evidence for one of the following conditions:

  * an underlying infectious disease
  * chromosomal abnormality
  * metabolic disorder
  * specific brain related disorder (such as tuberous sclerosis)
  * history of fetal cytomegalovirus infection
  * birth asphyxia
  * a history of major head injury
  * a chronic use of non-steroidal anti-inflammatory drugs, (NSAID)
  * known brain damage
* Epilepsy
* Abnormal Electro-cardiogram (ECG)
* Epileptiform EEG
* Use of psychostimulants, anti-depressants, neuroleptics or anti-convulsive agents within the past month.
* Lack of cooperation in the screening phase
C: Inclusion Criteria:

* Meet DSM-5 criteria for Autism Spectrum Disorder confirmed by the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule- Generic (ADOS-G)
* Children between the ages of 5-12 years of age
* Language delay (lack of fluent phrase speech) reflected by use of ADOS Module 1 or 2
* Must be on stable medication regimens for at least three months prior to enrollment, assuming the concomitant medication is safe for use with IGF-1

Exclusion Criteria:

* Closed epiphyses
* Active or suspected neoplasia
* Intracranial hypertension
* Hepatic insufficiency
* Renal insufficiency
* Cardiomegaly/valvulopathy
* History of allergy to IGF-1
* Patients with comorbid conditions deemed too medically compromised to tolerate the risk of experimental treatment with IGF-1
D: 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

Answer: B