Oxytocin-based Pharmacotherapy for Autism Spectrum Disorders: Investigating the Neural and Behavioral Effects of a Promising Intervention Approach
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- KU Leuven
- 入组人数
- 40
- 主要终点
- Change From Baseline in Brain Connectivity During Rest (Resting-state fMRI) After a Single Dose of Nasal Spray
研究概览
简要总结
The current trial aims to explore the neural and behavioral effects of oxytocin in autism spectrum disorders (ASD). Oxytocin is a nonapeptide produced by the paraventricular and supraoptic nuclei of the hypothalamus and is known to play a pivotal role in a variety of complex social behaviors. Initial studies showed that intranasal administration of oxytocin can have a positive effect on social functioning in ASD.
However, future studies are necessary to explore whether and how oxytocin effects neural processes in the brain underlying these behavioral improvements. This trial will not only measure behavioral enhancements, but will specifically focus on elucidating the associated neurophysiological changes by guiding the administration of oxytocin with regular neurophysiological assessments.
详细描述
The present study is a monocentric, between-subjects, randomized, placebo-controlled trial. The investigators will recruit approximately 40 young-adult, male individuals with a clinical diagnosis of Autism Spectrum Disorder (ASD). Participants will be randomly allocated to an experimental group (Oxytocin (OT)) and a control group (Placebo (PL)). All participants will receive the same frequency and duration of intervention. Behavioral and neural outcome measures will be assessed at multiple time points in a period of a year. Participants will be tested at 5 occasions: before and after a single dose of nasal spray, after multiple doses of nasal spray (1 daily dose of nasal spray during 4 weeks), after a 4-week retention period and after a 1-year retention period. At each time point participants will be tested at both the behavioral and neural level. Test performance of both participant groups (OT vs PL) will be compared by measuring reaction times and accuracy rates in a computerized task assessing a person's ability to recognize bodily emotional states from point light displays. In addition, attachment, social functioning, restricted behaviour, general quality of life and mood will be assessed via self-reported questionnaires.
Functional MRI measurements will be performed in a 3T MR Philips Intera scanner. Before scanning, subjects will undergo a training session to familiarize them with the task instructions. In addition to the fMRI measurements, resting state fMRI and Diffusion Tensor Imaging (DTI) will also be performed to reveal alterations of the functional and structural connectivity between critical regions.
Statistical analysis of the behavioral data will have a between-subject factor of group (OT vs PL) and within-subject factors of time (change-from-baseline). Image analysis will be performed with Statistical Parametric Mapping (SPM) software. The investigators will contrast for either decreased or increased activation, as different regions may show divergent changes due to the received nasal spray (either OT or PL).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Clinical diagnosis of Autism Spectrum Disorder, Asperger Syndrome or Autism
- •Age between 18 and 40 years old
排除标准
- •Associated neuro(psycho)logical disorder (i.e. epilepsy, concussion, stroke)
- •Eye sight worse than + or - 7
- •Genetic syndrome
- •Color blindness
- •Any contraindication to neuroimaging research as assessed with the MRI screening list:
- •MRI contraindications:
- •pacemaker, implanted defibrillator, ear implant / a cochlear implant, insulin or implanted pump, a neurostimulator or VP shunt, any metallic object in the eyes (metallic fragments)
研究组 & 干预措施
Syntocinon (Oxytocin, product code RVG 03716)
Administration via nasal spray
干预措施: Syntocinon (Oxytocin) (Drug)
Placebo (Physiological water(sodium chloride (NaCl) solution))
Administration via nasal spray
干预措施: Placebo (Physiological water (solution of sodium chloride (NaCl) in water)) (Other)
结局指标
主要结局
Change From Baseline in Brain Connectivity During Rest (Resting-state fMRI) After a Single Dose of Nasal Spray
时间窗: Value at 30 minutes minus value at baseline
Change From Baseline in Brain Connectivity During Rest (Resting-state fMRI) After a Single Dose of Nasal Spray Amygdala connectivity (Change-from-baseline z-transformed r-value) Higher z-transformed r-value indicates higher connectivity (higher correlated brain activity)
Change From Baseline in Brain Connectivity During Rest (Resting-state fMRI) After 8 Weeks, Including 4 Weeks Without Nasal Spray
时间窗: Value at 8 weeks minus value at baseline
Change from baseline in brain connectivity during rest (resting-state fMRI) after 8 weeks, including 4 weeks without nasal spray Amygdala connectivity (Change-from-baseline z-transformed r-value) Higher z-transformed r-value indicates higher connectivity (higher correlated brain activity)
Change From Baseline in Brain Activity During Task (Task-based fMRI) After a Single Dose of Nasal Spray
时间窗: Value at 30 minutes minus value at baseline
Change From Baseline in Task-related Brain Activity During Biological Motion Recognition Task (Task-based fMRI) After a Single Dose of Nasal Spray BOLD response (Blood-oxygen-level-dependent response)
Change From Baseline in Brain Activity During Task (Task-based fMRI) After 52 Weeks, Including 48 Weeks Without Nasal Spray
时间窗: Value at 52 weeks minus value at baseline
Change From Baseline in Task-related Brain Activity During Biological Motion Recognition Task (Task-based fMRI) after 52 weeks, including 48 weeks without nasal spray BOLD response (Blood-oxygen-level-dependent response)
Change From Baseline in Brain Activity During Task (Task-based fMRI) After 8 Weeks, Including 4 Weeks Without Nasal Spray
时间窗: Value at 8 weeks minus value at baseline
Change From Baseline in Task-related Brain Activity During Biological Motion Recognition Task (Task-based fMRI) after 8 weeks, including 4 weeks without nasal spray BOLD response (Blood-oxygen-level-dependent response)
Change From Baseline in Brain Activity During Task (Task-based fMRI) After 4 Weeks of Nasal Spray
时间窗: Value at 4 weeks minus value at baseline
Change From Baseline in Task-related Brain Activity During Biological Motion Recognition Task (Task-based fMRI) after 4 weeks of nasal spray BOLD response (Blood-oxygen-level-dependent response)
Change From Baseline in Brain Connectivity During Rest (Resting-state fMRI) After 52 Weeks, Including 48 Weeks Without Nasal Spray
时间窗: Value at 52 weeks minus value at baseline
Change from baseline in brain connectivity during rest (resting-state fMRI) after 52 weeks, including 48 weeks without nasal spray Amygdala connectivity (Change-from-baseline z-transformed r-value) Higher z-transformed r-value indicates higher connectivity (higher correlated brain activity)
Change From Baseline in Brain Connectivity During Rest (Resting-state fMRI) After 4 Weeks of Nasal Spray
时间窗: Value at 4 weeks minus value at baseline
Change from baseline in brain connectivity during rest (resting-state fMRI) after 4 weeks of nasal spray Amygdala connectivity (Change-from-baseline z-transformed r-value) Higher z-transformed r-value indicates higher connectivity (higher correlated brain activity)
次要结局
- Change From Baseline in Performance on the Emotion Recognition Task (Accuracy/ Reaction Time) After 4 Weeks of Nasal Spray(Value at 4 weeks minus value at baseline)
- Change From Baseline in Scores on Questionnaire Assessing Mood After a Single Dose of Nasal Spray(Value at 30 minutes minus value at baseline)
- Change From Baseline in Performance on the Emotion Recognition Task (Accuracy/ Reaction Time) After 52 Weeks (Including 48 Weeks Without Nasal Spray)(Value at 52 weeks minus value at baseline)
- Change From Baseline in Performance on the Emotion Recognition Task (Accuracy/Reaction Time) After a Single Dose of Nasal Spray(Value at 30 minutes minus value at baseline)
- Change From Baseline in Performance on the Emotion Recognition Task (Accuracy/ Reaction Time) After 8 Weeks (Including 4 Weeks Without Nasal Spray)(Value at 8 weeks minus value at baseline)
- Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 4 Weeks of Nasal Spray(Value at 4 weeks minus value at baseline)
- Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 8 Weeks, Including 4 Weeks Without Nasal Spray(Value at 8 weeks minus value at baseline)
- Change From Baseline in Informant-based/ Self-report Scores on Questionnaires Assessing Attachment, Social Functioning, Quality of Life and Mood After 52 Weeks, Including 48 Weeks Without Nasal Spray(Value at 52 weeks minus value at baseline)