Clinical trial NCT02611921: Study of Intranasal Ketamine for Social Impairment in Autism Spectrum Disorder
Official title: Intranasal Ketamine Use in Autism Spectrum Disorder: A Placebo-Controlled Crossover Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Autism Spectrum Disorder
Keywords: Ketamine
Social Impairment
Autism
Autistic Disorder
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
Collaborators: name: Roivant Sciences, Inc.
name: Cures Within Reach
First posted: 2015-11-23
Enrollment: 21
Sex: ALL
Minimum age (years): 12
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to determine if intranasal ketamine shows initial evidence of safety, tolerability and efficacy for the treatment of social impairment in individuals with Autism Spectrum Disorder.

Detailed description: To address the significant need for effective treatment of core symptoms of Autism Spectrum Disorder (ASD), this trial is designed as a double-blind, placebo-controlled crossover pilot study of intranasal ketamine in 24 individuals with ASD ages 12- 30 years using a novel quantitative eye-tracking outcome measure to assess impact of the drug on social impairment. Additionally, to develop a ketamine-focused personalized medicine approach in ASD, the investigators will include pharmacokinetic, molecular pharmacodynamic, and electrophysiological assessments into initial systematic study.

Eligibility criteria: Inclusion Criteria:

* Ages 12 to 30 years old.
* Weight equal to or greater than 50 kg.
* General good health as determined by physical exam, medical history, laboratory work up, and EKG.
* Diagnostic and Statistical Manual of Mental Disorders 5th Edition diagnosis of autism spectrum disorder (not associated with Fragile X Syndrome or other known genetic syndrome) as confirmed by the Autism Diagnostic Observation Schedule at screen or previous (within last 5 years) if available.
* Valid Intelligence Quotient (IQ) score greater than or equal to 50 as confirmed via testing (Leiter-3) at screen or previous (within last 5 years, any valid testing acceptable).
* Clinical Global Impressions-Severity score of 4 (Moderately Ill).
* Score of 10 on the Social Withdrawal subscale of the Aberrant Behavior Checklist.
* Stable dosing of all concomitant psychotropic medications for five half-lives prior to screening visit and during the study.
* Presence of parent/guardian or significant other or caregiver willing to serve as informant for behavioral outcome measures.

Exclusion Criteria:

* Presence of co-morbid schizophrenia, schizoaffective disorder, bipolar disorder with psychosis, bipolar disorder or psychosis not otherwise specified. Comorbid diagnoses determined by psychiatrist clinical interview and use of Diagnostic and Statistical Manual of Mental Disorders 5th Edition diagnostic criteria.
* History of drug or alcohol abuse.
* Presence of cardiac disease including coronary artery disease, congestive heart failure, or uncontrolled hypertension per medical history (individuals with ≥ 2 blood pressure readings of ≥140/90 during screen/baseline will be excluded).
* Airway instability, tracheal surgery, or tracheal stenosis per medical history.
* Central nervous system masses or hydrocephalus per medical history.
* Porphyria, thyroid disorder, or thyroid medication use per medical history.
* Glaucoma or other cause of increased intraocular pressure per medical history.
* Allergy to ketamine.
* Current use of drugs with concomitant modification of non-competitive N-methyl-D-aspartate glutamate activity (acamprosate, amantadine, memantine, d-cycloserine etc.)
* For female subjects of child bearing potential, a positive pregnancy test.
* Any major chronic medical or chronic respiratory illness considered to be uncontrolled by the Principal Investigator.
* Inability to tolerate study procedures or study drug per the discretion of the Principal Investigator.

Primary outcomes:
measure: Change in Social Withdrawal subscale score of the Aberrant Behavior Checklist (ABC)
timeFrame: Social withdrawal subscale change from baseline to final visit on day 35 ± 2 days
Secondary outcomes:
measure: Change in the Clinician-rated CGI Improvement scale (CGI-I)
timeFrame: CGI-I change from baseline to final visit on day 35 ± 2 days
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Cincinnati Childrens Hospital Medical Center
state: Ohio
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Logan K Wink, MD
role: PRINCIPAL_INVESTIGATOR
References: