Brain Imaging of Intranasal Oxytocin Treatment in Autism

NCT01945957 | Completed Phase 1

• 2 other identifiers: 12-2622U54HD079124-01
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

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.

Conditions

Autism Spectrum Disorders

Keywords

autism; brain; functional magnetic resonance imaging; oxytocin

Outcome Measures

Primary Outcomes (2)

• Aim 1a. fMRI Activation Analysis/Connectivity

  Activation data will be analyzed using FEAT within FSL (Oxford University, U.K.). Onset times of events will be used to model BOLD signal responses containing a regressor for each response type convolved with a double-γ function. A priority region of interest will be the VTA and NAc which will be analyzed via anatomically defined ROI's. Connectivity Analysis:Time series will be extracted from ROIs using FSL Featquery for each participant and averaged separately for each Treatment (OT, placebo) and Trial Type (rewarded, unrewarded) condition (seed and target regions will be functionally defined on the basis of task response). Correlation coefficients will be transformed using a Fisher r-to z transformation. Mean z-transformed values will then be computed across participants and ROI pairs, and then converted back to correlation coefficients.

  30, 75 minutes post dose

• Aim 1b. Proportion of Time Attending to Social Stimuli (Eye Tracking)

  The eye tracking task involves the participant looking at a series of images in which a person's face occupies ½ the screen and a complex object occupies the other half of the screen that are presented for \~20 seconds each on a computer monitor. The participant is only told to look at the screen and sits approximately 18-24 inches in front of a computer monitor with built in cameras and lights to track eye movement. This is referred to as competitive attention task to social and nonsocial stimuli. Eye tracking will be assessed via a Tobii 1750 eye tracker or via mobile eye tracking, immediately after the fMRI scan, participants will participate in a 10 min lab-based eye tracking task in which a series of paired social and nonsocial stimuli are displayed for 10 seconds.

  pre dose and then 30, 60,120-240 minutes post dose

Secondary Outcomes (5)

• Plasma Oxytocin (OT) levels in aim 1b. and 2b.

  pre dose and then 30, 120, 240 and 360 minutes post dose

• Salivary Oxytocin (OT) levels for all aims.

  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.

• SRS-Social Responsiveness Scale

  at the scanner visit and eye-tracking visit

• Pervasive Developmental Disorders Behavior Inventory-Screening Version (PDDBI-SV)

  at the scanner visit and eye-tracking visit

• ABC-lethargy/social withdrawal subscale

  at the scanner visit and eye-tracking visit

Other Outcomes (1)

• 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

  at the scanner visit and eye-tracking visit

Study Arms (2)

OT (24 IU)

EXPERIMENTAL

Phase I Aim 1a. (fMRI) Will determine the effect of oxytocin dose (24 IU) on neural activation and connectivity compared to placebo. Aim 1 b (eye-tracking) will occur on a separate visit from fMRI scanning and will also assess response to oxytocin in an eye-tracking task (social vs. non-social image).

Drug: Oxytocin

OT (8 IU and 40IU)

EXPERIMENTAL

Each phase will require a separate subject consent. Phase II Aim 2a. (fMRI) Will determine the effect of oxytocin dose (8 or 40 IU) on neural activation and connectivity. Aim 1 b (eye-tracking) will occur on a separate visit from fMRI scanning and will also assess response to oxytocin (8 or 40 IU) in an eye-tracking task (social vs. non-social image).

Drug: Oxytocin

Interventions

Oxytocin DRUG

For Phase I, subjects will be randomized to receive either 24IU (6 sprays) of active oxytocin or 6 sprays of placebo (3 sprays per nostril) For Phase II, subjects will be randomized to receive either 8 IU or 40 IU of oxytocin.

Also known as: Syntocinon

OT (24 IU); OT (8 IU and 40IU)

Eligibility Criteria

• Age: 6 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Duke University: collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27517, United States

Location

MeSH Terms

Conditions

Autism Spectrum Disorder; Autistic Disorder

Interventions

Oxytocin

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Gabriel Dichter, PhD

  The University of North Carolina at Chapel Hill, Duke University

  PRINCIPAL INVESTIGATOR

• Allen Song, PhD

  Duke University

  PRINCIPAL INVESTIGATOR

• Linmarie Sikich, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2013
• First Posted: September 19, 2013
• Study Start: September 1, 2014
• Primary Completion: January 1, 2017
• Study Completion: January 1, 2017
• Last Updated: April 25, 2017

Record last verified: 2016-08

Locations

US (1)