Target Engagement for Intranasal Oxytocin in Autism Spectrum Disorders, an fMRI Dose Response Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 51
- 试验地点
- 1
- 主要终点
- Resting State Functional Connectivity (rsFC) Salience Network (Anterior Cingulate Cortex (ACC) and Insula Versus Visual Cortex)
研究概览
简要总结
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.
详细描述
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:
- 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
- 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)
- 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Autism Spectrum Disorder (ASD)
Male participants diagnosed with ASD will receive 12 puffs (6 in each nostril) of intranasal oxytocin (syntocinon) and placebo (assigned randomly) during 4 study visits.
干预措施: 8 International Units (IU) of Oxytocin (Drug)
Autism Spectrum Disorder (ASD)
Male participants diagnosed with ASD will receive 12 puffs (6 in each nostril) of intranasal oxytocin (syntocinon) and placebo (assigned randomly) during 4 study visits.
干预措施: 24IU of Oxytocin (Drug)
Autism Spectrum Disorder (ASD)
Male participants diagnosed with ASD will receive 12 puffs (6 in each nostril) of intranasal oxytocin (syntocinon) and placebo (assigned randomly) during 4 study visits.
干预措施: 48IU of Oxytocin (Drug)
Autism Spectrum Disorder (ASD)
Male participants diagnosed with ASD will receive 12 puffs (6 in each nostril) of intranasal oxytocin (syntocinon) and placebo (assigned randomly) during 4 study visits.
干预措施: Placebo (Drug)
Healthy Control
Age matched healthy controls will receive placebo intranasal spray (12 puffs, 6 per nostril) during one study visit.
干预措施: Placebo (Drug)
结局指标
主要结局
Resting State Functional Connectivity (rsFC) Salience Network (Anterior Cingulate Cortex (ACC) and Insula Versus Visual Cortex)
时间窗: Post Intervention (Up to 40 minutes after receiving spray) at Study Visits 1, 2, 3 and 4
Investigators will study the effects of intranasal oxytocin (IN-OT) on the resting state functional connectivity between key socio-emotional and social salience brain regions using functional magnetic resonance imaging (fMRI). Resting state functional connectivity is a task-independent metric of brain activity that is based on correlations between low-frequency fluctuations of the blood oxygen level-dependent signal between several brain regions. It reflects the strength of a functional connection that is in good agreement with the underlying neuroanatomy and provides a system-level understanding of brain function. Z-scores represent the number of standard deviations from the mean of 0 and range from -3 to +3, and z-scores greater than 0 indicate greater than average resting state functional connectivity.
Percent Change in Blood Oxygen Level Dependent (BOLD) Activity During Ball-Game Task
时间窗: Post Intervention (up to 70 minutes) at Study Visits 1, 2, 3, and 4
BOLD activity in social-emotional brain regions during the perception of emotional facial videos were measured during the ball-game task. Mean percent change in contrast of parameter estimates in anatomical regions of interest are presented here. A positive value indicates increased BOLD activity while a negative value indicates decreased BOLD activity.
Oxytocin Plasma Concentration
时间窗: Visits 1, 2, 3 and 4 (before spray and 5 minutes after spray)
Plasma concentration of oxytocin prior to administration of study intervention and after administration of study intervention will be compared between the different dose levels and placebo. Plasma concentration of oxytocin is expected to increase following administration of intranasal oxytocin.
Blood Oxygen Level Dependent (BOLD) Activity in Response to Social Cues
时间窗: Post Intervention (Up to 70 minutes) at Study Visits 1, 2, 3, and 4
BOLD activity level was assessed via fMRI during completion of the face perception task (FPT) of emotional and neutral faces. BOLD scores are reported on a z-scale, with the mean, standard deviation and the minimum and the maximum. This refers to the non-thresholded z-scores that are obtained for each dose before conducting small volume correction analysis.
次要结局
- Social Learning Test (SLT) Reaction Time(Post Intervention (Up to 130 minutes) at Study Visits 1, 2, 3 and 4)
- Rate of Smiling During Global Clinical Interview(Post Intervention (Up to 180 minutes after receiving spray) at Study Visits 1, 2, 3 and 4)
- Milliseconds of Visual Fixation(Post Intervention (Up to 50 minutes) at Study Visits 1, 2, 3 and 4)
研究者
Elissar Andari
Adjunct Assistant Professor
Emory University