Can Brain Activation and Connectivity Predict Treatment Response to Two Serotonergic Medications (Citalopram and Tianeptine) in Subjects With Autism Spectrum Disorders (ASD)?
试验速览
- 阶段
- 不适用
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Brain excitation and inhibition response to pharmacological stimulation as assessed by magnetic resonance spectroscopy
研究概览
简要总结
This study investigates brain response to single acute dose of citalopram, tianeptine, and placebo in males with and without autism spectrum disorder.
详细描述
There is increasing evidence that the serotonin (5-HT) system is implicated in autism spectrum disorder (ASD), with the standard treatment for depression and anxiety in both the general population and ASD includes targeting the 5-HT system with selective serotonin reuptake inhibitors (SSRIs) citalopram. Some individuals with ASD have a good treatment response but others do not. Tianeptine, which has a different mechanism of action to SSRIs, is also an effective antidepressant. As it is unlikely that all individuals with ASD will respond to the same treatment, the investigators aim to conduct a pharmacological magnetic resonance imaging (phMRI) investigation to elucidate the neural mechanisms underlying the response to citalopram and tianeptine in ASD. The investigators are inviting 50 male adults with ASD and 50 male adults without ASD. Each participant receives each drug once (20 mg citalopram, 12.5 mg tianeptine, or placebo) and MRI is used to obtain measures of brain biochemistry, activity, and connectivity. The investigators also acquire data from questionnaires, electroencephalography, neurocognitive tests and blood samples.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
盲法说明
Participants and investigators are blinded to the drug condition.
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Intelligence Quotient (IQ) above 70
- •Has capacity and is capable of giving written informed consent
- •Able to read, comprehend and record information written in English
- •Bodyweight of <120 kg and BMI within the range 18.5 - 33 kg/m2 (inclusive).
- •Not taking medication directly affecting gamma-aminobutyric acid (GABA) neurotransmission for at least the past 4 weeks
- •Not taking medication directly affecting the serotonergic system for at least the past 4 weeks
- •ASD only: Diagnosis of Autism Spectrum Disorder (ICD 10-R criteria, confirmed using the Autism Diagnostic Interview (ADI) and/or ADOS) including atypical autism
- •ASD only: Being recommended drug therapy for symptoms of depression and/or anxiety
- •Controls only: No diagnosis of Autism Spectrum Disorder (ICD 10-R criteria, confirmed using the ADI and/or ADOS)
- •Controls only: No diagnosis of major depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders (DSM) IV or ICD 10.
排除标准
- •Current risk of self-harm
- •Acute risk of suicidality (e.g., current suicidal ideations)
- •Age < 18 years or > 60 years old.
- •Taking medication directly affecting the serotonergic system (e.g. SSRIs, Tricyclic antidepressants)
- •Taking medication directly affecting GABA neurotransmission (e.g. antiepileptic drugs, and benzodiazepines)
- •Taking antipsychotic medication or medication for attention deficit hyperactivity disorder (ADHD) for the past 4 weeks
- •History of dependence to alcohol or substances of abuse (excluding nicotine)
- •Major mental illness (e.g. psychosis), or a learning disability (mental retardation)
- •Needle phobia
- •Medical/genetic disorder associated with ASD
- •Diagnosed and treated for hyperkinesis or Tourette's syndrome
- •Allergy to food colouring
研究组 & 干预措施
Citalopram, Placebo, Tianeptine
Dose order: Citalopram, Placebo, Tianeptine
干预措施: Citalopram (Drug)
Placebo, Citalopram, Tianeptine
Dose order: Placebo, Citalopram, Tianeptine
干预措施: Placebo (Drug)
Placebo, Citalopram, Tianeptine
Dose order: Placebo, Citalopram, Tianeptine
干预措施: Citalopram (Drug)
Placebo, Citalopram, Tianeptine
Dose order: Placebo, Citalopram, Tianeptine
干预措施: Tianeptine (Drug)
Placebo, Tianeptine, Citalopram
Dose order: Placebo, Tianeptine, Citalopram
干预措施: Placebo (Drug)
Placebo, Tianeptine, Citalopram
Dose order: Placebo, Tianeptine, Citalopram
干预措施: Citalopram (Drug)
Placebo, Tianeptine, Citalopram
Dose order: Placebo, Tianeptine, Citalopram
干预措施: Tianeptine (Drug)
Citalopram, Placebo, Tianeptine
Dose order: Citalopram, Placebo, Tianeptine
干预措施: Placebo (Drug)
Citalopram, Placebo, Tianeptine
Dose order: Citalopram, Placebo, Tianeptine
干预措施: Tianeptine (Drug)
Citalopram, Tianeptine, Placebo
Dose order: Citalopram, Tianeptine, Placebo
干预措施: Placebo (Drug)
Citalopram, Tianeptine, Placebo
Dose order: Citalopram, Tianeptine, Placebo
干预措施: Citalopram (Drug)
Citalopram, Tianeptine, Placebo
Dose order: Citalopram, Tianeptine, Placebo
干预措施: Tianeptine (Drug)
Tianeptine, Placebo, Citalopram
Dose order: Tianeptine, Placebo, Citalopram
干预措施: Placebo (Drug)
Tianeptine, Placebo, Citalopram
Dose order: Tianeptine, Placebo, Citalopram
干预措施: Citalopram (Drug)
Tianeptine, Placebo, Citalopram
Dose order: Tianeptine, Placebo, Citalopram
干预措施: Tianeptine (Drug)
Tianeptine, Citalopram, Placebo
Dose order: Tianeptine, Citalopram, Placebo
干预措施: Placebo (Drug)
Tianeptine, Citalopram, Placebo
Dose order: Tianeptine, Citalopram, Placebo
干预措施: Citalopram (Drug)
Tianeptine, Citalopram, Placebo
Dose order: Tianeptine, Citalopram, Placebo
干预措施: Tianeptine (Drug)
结局指标
主要结局
Brain excitation and inhibition response to pharmacological stimulation as assessed by magnetic resonance spectroscopy
时间窗: In the months 1-2 following the last day of scanning
The measure of brain excitation and inhibition response to placebo, citalopram, and tianeptine includes the following: Assessment of the ratio of brain excitation and inhibition (measured as the balance of excitatory and inhibitory neurotransmitters) using proton magnetic resonance spectroscopy.
Brain activation response to pharmacological stimulation as assessed by functional magnetic resonance imaging
时间窗: In the months 3-4 following the last day of scanning
The measure of brain activation response to placebo, citalopram, and tianeptine includes the following: Assessment of the blood-oxygen-level-dependent activation during tasks using functional magnetic resonance imaging.
Brain connectivity response to pharmacological stimulation as assessed by resting-state functional magnetic resonance imaging
时间窗: In the months 5-6 following the last day of scanning
The measure of brain connectivity response to placebo, citalopram, and tianeptine includes the following: Assessment of the regional homogeneity during resting-state using functional magnetic resonance imaging.
次要结局
未报告次要终点
研究者
Dr Grainne McAlonan
Deputy head of department
King's College London