Clinical trial NCT01945957: Brain Imaging of Intranasal Oxytocin Treatment in Autism
Official title: Brain Imaging and Eye-tracking in Response to Intranasal Oxytocin Treatment in Children and Adolescents With Autism
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Autism Spectrum Disorders
Keywords: autism
brain
functional magnetic resonance imaging
oxytocin
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Duke University
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2013-09-19
Enrollment: 33
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: This is a 4 part study:

Phase 1a. -functional magnetic resonance imaging (fMRI) ( with oxytocin 24 IU vs. placebo = oxytocin 0 IU) - funded by grant #U54 HD079124-01, Phase 1b-eye-tracking(oxytocin 24 IU vs. placebo = oxytocin 0 IU), Phase 2a. fMRI (oxytocin 8 IU vs. oxytocin 40IU), Phase 2b. -eye-tracking (oxytocin 8IU vs. oxytocin 40IU). Time course of effect will also be assessed within session.

Detailed description: We hypothesize that intranasal oxytocin treatment (OT) of individuals with an autism spectrum disorder (ASD) will:

Hypothesis 1a. will produce greater increases in Ventral Tegmental Area (VTA) and Nucleus Accumbens (NAc) activation during social reward anticipation compared to placebo, providing evidence that OT increases activation in brain regions critical for social motivation. (NICHD funding for this section/aim- Dr. Joe Piven -U54 HD079124-01)

Hypothesis 1b. will spend proportionally more time attending to the social image on a screen vs. the non-social image compared to placebo.

Hypothesis 2a. will produce differential effects in VTA and NAc activation during social reward anticipation compared with the oxytocin 8 IU vs. oxytocin 40 IU dose, providing evidence that OT dose-dependently increases activation in brain regions critical for social motivation.

Hypothesis 2b. will differentially attend to the social image on a screen vs. the non-social image compared in the oxytocin 8 IU vs. oxytocin 40 IU dose, providing evidence that OT dose-dependently changes the value of social stimuli.

Eligibility criteria: Inclusion Criteria:

* Between 6 and 18 years of age, inclusive
* Have a clinical diagnosis of an autism spectrum disorder confirmed according to the Autism Diagnostic Observation Scale (ADOS, Lord et al., 1989). Diagnosis may also be confirmed using the Autism Diagnostic Interview-Revised (ADI-R).
* Male or female of any race or ethnicity
* Ambulatory status (outpatient) at time of assent/consent
* Estimated IQ greater than or equal to 70 and capable of making an informed decision based on assessment of their understanding and judgment

Exclusion Criteria:

* History of neurological injury: head trauma, poorly-controlled seizure disorder (i.e. seizure within the preceding six month period), stroke, prior neurosurgery, or under the care of a neurologist or neurosurgeon as determined by interview
* History of claustrophobia
* Implanted medical devices, implanted metal debris, shrapnel, certain tattoos, or permanent makeup that is contraindicated for MRI. Participants fill out a detailed questionnaire on the day of scanning to identify potential MRI risks
* Subjects with a medical condition that might interfere with the conduct of the study, confound interpretation of the study results, or endanger their own well-being. This includes, but is not limited to: Rett Syndrome, impairment of renal function, evidence or history of malignancy or any significant hematological, endocrine, cardiovascular (including any rhythm disorder or uncontrolled hypertension), respiratory, hepatic, or gastrointestinal disease
* Marked sensory impairment such as deafness or blindness that would interfere with the conduct of the study
* Pregnant or nursing because of the unknown effects of oxytocin to unborn babies and/or nursing infants. All females of child-bearing potential will be administered a serum pregnancy test at screening and at any point during the study at physician discretion. Refusal to undergo a pregnancy test will result in exclusion from the study. We will share results of a pregnancy test with the subject's legal guardian.
* Refusal to do pregnancy testing with understanding that guardian will be informed of positive test results
* Inability or refusal of sexually active female subjects (who have begun menses) to utilize two medically accepted barrier forms of birth control
* Use of hormonal birth control
* Subjects who have a history of an anaphylactic reaction from prior treatment with oxytocin (nasal spray)
* Inability of caretakers to speak English
* Absence of a consistent caretaker to report on symptoms
* Subjects who, in the Investigator's opinion, might not be suitable for the study

Primary outcomes:
measure: Aim 1a. fMRI Activation Analysis/Connectivity
timeFrame: 30, 75 minutes post dose
measure: Aim 1b. Proportion of Time Attending to Social Stimuli (Eye Tracking)
timeFrame: pre dose and then 30, 60,120-240 minutes post dose
Secondary outcomes:
measure: Plasma Oxytocin (OT) levels in aim 1b. and 2b.
timeFrame: pre dose and then 30, 120, 240 and 360 minutes post dose
measure: Salivary Oxytocin (OT) levels for all aims.
timeFrame: pre dose and then 30, 60, 120-240 minutes post dose for aims 1b, 2b. predose, 25min and 95 min post dose for aims 1a, 2a.
measure: SRS-Social Responsiveness Scale
timeFrame: at the scanner visit and eye-tracking visit
measure: Pervasive Developmental Disorders Behavior Inventory-Screening Version (PDDBI-SV)
timeFrame: at the scanner visit and eye-tracking visit
measure: ABC-lethargy/social withdrawal subscale
timeFrame: at the scanner visit and eye-tracking visit
Other outcomes:
measure: Caregivers will complete the Hollingshead Two-Factor Index of Social Position (only if not done previously in trial), the Repetitive Behavior Scale (revised), and the other subscales of the Aberrant Behavior Checklist
timeFrame: at the scanner visit and eye-tracking visit
Locations:
city: Chapel Hill
country: United States
facility: The University of North Carolina at Chapel Hill
state: North Carolina
Study officials:
affiliation: The University of North Carolina at Chapel Hill, Duke University
name: Gabriel Dichter, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Allen Song, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Linmarie Sikich, MD
role: PRINCIPAL_INVESTIGATOR
References: