Study of Intranasal Ketamine for Social Impairment in Autism Spectrum Disorder

Intranasal Ketamine Use in Autism Spectrum Disorder: A Placebo-Controlled Crossover Pilot Study

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.

Study Overview

• Status: Completed
• Conditions: Autism Spectrum Disorder
• Intervention / Treatment: Drug: Ketamine; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Childrens Hospital Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 30 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Crossover Group: Ketamine verses Placebo; Phase 1: Two ascending doses of intranasal ketamine Two week washout Phase 2: Two doses of placebo	Drug: Ketamine; Ketamine will be compounded into a mucosal atomization device and self-administered or administered with assistance of a caregiver/study coordinator; Other Names: Ketalar; Drug: Placebo; Placebo will delivered as an atomized saline spray which will be self-administered or administered with assistance of a caregiver/study coordinator; Other Names: Saline
Experimental: Crossover Group: Placebo verses Ketamine; Phase 1: Two doses of placebo Two week washout Phase 2: Two ascending doses of intranasal ketamine	Drug: Ketamine; Ketamine will be compounded into a mucosal atomization device and self-administered or administered with assistance of a caregiver/study coordinator; Other Names: Ketalar; Drug: Placebo; Placebo will delivered as an atomized saline spray which will be self-administered or administered with assistance of a caregiver/study coordinator; Other Names: Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Social Withdrawal subscale score of the Aberrant Behavior Checklist (ABC)	The ABC is the gold standard parent/caregiver reported behavioral outcome measure for use in developmental disability clinical trials.	Social withdrawal subscale change from baseline to final visit on day 35 ± 2 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Clinician-rated CGI Improvement scale (CGI-I)	The CGI-I is a 7-point scale designed to measure symptomatic change at a specific time as compared to baseline. The CGI-I will be focused on the target symptoms of social impairment. CGI-I is a gold standard measure of potential change with treatment in placebo- controlled pharmacotherapy trials in ASD	CGI-I change from baseline to final visit on day 35 ± 2 days

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati
• Collaborators: Cures Within Reach; Roivant Sciences, Inc.
• Investigators: Principal Investigator: Logan K Wink, MD, Children's Hospital Medical Center, Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2015
• Primary Completion (Actual): May 7, 2018
• Study Completion (Actual): May 7, 2018

Study Registration Dates

• First Submitted: November 17, 2015
• First Submitted That Met QC Criteria: November 19, 2015
• First Posted (Estimate): November 23, 2015

Study Record Updates

• Last Update Posted (Actual): October 12, 2018
• Last Update Submitted That Met QC Criteria: October 10, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Ketamine; Autism; Autistic Disorder; Social Impairment
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Neurodevelopmental Disorders; Disease; Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: 2015-2494

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No