Clinical trial NCT03033784: Autism Oxytocin Brain Project
Official title: Target Engagement for Intranasal Oxytocin in Autism Spectrum Disorders, an fMRI Dose Response Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Autism
Autism Spectrum Disorder
Keywords: Neuroscience
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2017-01-27
Enrollment: 51
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The main goal of the study is to look at the effects of intranasal oxytocin on the brain in Autism Spectrum Disorder (ASD). Oxytocin is a hormone that exists naturally in the body and the brain, affecting a wide range of social behaviors and emotions. The investigators will study the effects of different treatments (3 doses of oxytocin and one dose of placebo) on brain functional connectivity at rest in patients with ASD, using functional magnetic resonance imaging (fMRI). Investigators also seek to study how the effects of oxytocin treatment can be affected by genetic, immune and environmental factors.

Detailed description: This study consists of investigating the effects of several doses of acute administration of intranasal oxytocin on brain activity in adults with Autism Spectrum Disorder (ASD). There is increasing evidence for the role of intranasal oxytocin (IN-OT) in enhancing social skills in ASD. Nevertheless, there is still a need of determining target engagement for oxytocin's action on brain and behavior. Here, investigators are studying the effects of different doses of IN-OT on the modulation of behavioral outcomes and neural responses in a double blind crossover study in individuals with ASD.

The aims of the research are to:

1. Study the effects of IN-OT doses on the modulation of brain functional connectivity between key socio-emotional brain regions during resting state in ASD
2. Study the effects of IN-OT doses on the blood-oxygen-level dependent (BOLD) activity of key emotional and perceptual brain networks in response to social cues (such as faces)
3. Study the effects of IN-OT on the BOLD activity of brain regions during an interactive social environment (ball game) in ASD

Investigators will compare the neuroimaging and behavioral results of individuals with ASD to control healthy males who will receive intranasal placebo. Investigators are also investigating the role of genetic factors, behavioral or clinical sub-groups of ASD, immune and environmental factors in modulating the effect of IN-OT on brain and behavior.

Participants with ASD will undergo 4 clinical visits during which they receive various randomly assigned doses of intranasal oxytocin and placebo. Both participants and the experimenter will be blind to the type of the treatment administered.

There will be only one visit for healthy controls who will all receive placebo spray. The visit for healthy controls will be conducted in a single-blind design. The experimenter will be aware that the subject is receiving placebo. However, the participant will be told that he might receive oxytocin or placebo.

Eligibility criteria: Inclusion Criteria for ASD Participants:

* Have an ASD diagnosis based on the Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview (ADI) criteria, gold standards of research-based autism diagnosis
* Intelligence quotient (IQ) \> 70
* Normal or corrected-to-normal vision

Exclusion Criteria for ASD Participants:

* Recent occurrence of seizures (past 5 years)
* Brain damage or head trauma (can be included at discretion of PI and sponsor)
* Color blind
* Cardiovascular disease
* Presence of a severe medical problem
* Severe mental retardation
* Alcoholism or substance abuse
* Asthma (can be included at the discretion of study physician/nurse practitioner if episodes are infrequent and no active problems at time of the study)
* Migraine headaches (at the discretion of the nurse practitioner or the study physician)
* Claustrophobia (at discretion of study physician/designee/PI)
* Pacemakers, cochlear implants, surgical clips or metal fragments

Inclusion Criteria for Healthy Age-Matched Controls:

* IQ \> 70
* Normal or corrected-to-normal vision

Exclusion Criteria for Healthy Age-Matched Controls:

* History of seizures
* Neurological disorder
* Current psychiatric disorder
* Previous psychiatric disorder (can be included at discretion of PI)
* Current use of psychoactive drugs
* Previous use of psychoactive drugs (can be included at discretion of PI)
* Head trauma (can be included at discretion of PI)
* Alcoholism or substance abuse
* Cardiovascular disease
* Color blind
* Asthma (can be included at the discretion of study physician/nurse practitioner if episodes are infrequent and no active problems at time of the study)
* Migraine headaches (at the discretion of the nurse practitioner or the study physician)
* Claustrophobia (at discretion of study physician/designee/PI)
* Presence of a severe medical problem
* Severe mental retardation
* Pacemakers, cochlear implants, surgical clips or metal fragments

Primary outcomes:
measure: Resting State Functional Connectivity (rsFC) Salience Network (Anterior Cingulate Cortex (ACC) and Insula Versus Visual Cortex)
timeFrame: Post Intervention (Up to 40 minutes after receiving spray) at Study Visits 1, 2, 3 and 4
measure: Blood Oxygen Level Dependent (BOLD) Activity in Response to Social Cues
timeFrame: Post Intervention (Up to 70 minutes) at Study Visits 1, 2, 3, and 4
measure: Percent Change in Blood Oxygen Level Dependent (BOLD) Activity During Ball-Game Task
timeFrame: Post Intervention (up to 70 minutes) at Study Visits 1, 2, 3, and 4
measure: Oxytocin Plasma Concentration
timeFrame: Visits 1, 2, 3 and 4 (before spray and 5 minutes after spray)
Secondary outcomes:
measure: Rate of Smiling During Global Clinical Interview
timeFrame: Post Intervention (Up to 180 minutes after receiving spray) at Study Visits 1, 2, 3 and 4
measure: Milliseconds of Visual Fixation
timeFrame: Post Intervention (Up to 50 minutes) at Study Visits 1, 2, 3 and 4
measure: Social Learning Test (SLT) Reaction Time
timeFrame: Post Intervention (Up to 130 minutes) at Study Visits 1, 2, 3 and 4
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University
state: Georgia
Study officials:
affiliation: Emory University
name: Elissar Andari, PhD
role: PRINCIPAL_INVESTIGATOR
References: