Brain Response to Serotonergic Medications in ASD
- Conditions
- Autism Spectrum Disorder
- Interventions
- Registration Number
- NCT04145076
- Lead Sponsor
- King's College London
- Brief Summary
This study investigates brain response to single acute dose of citalopram, tianeptine, and placebo in males with and without autism spectrum disorder.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- Male
- Target Recruitment
- 100
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Tianeptine, Placebo, Citalopram Placebo Dose order: Tianeptine, Placebo, Citalopram Placebo, Citalopram, Tianeptine Placebo Dose order: Placebo, Citalopram, Tianeptine Placebo, Tianeptine, Citalopram Placebo Dose order: Placebo, Tianeptine, Citalopram Citalopram, Placebo, Tianeptine Placebo Dose order: Citalopram, Placebo, Tianeptine Citalopram, Tianeptine, Placebo Placebo Dose order: Citalopram, Tianeptine, Placebo Tianeptine, Citalopram, Placebo Placebo Dose order: Tianeptine, Citalopram, Placebo Placebo, Citalopram, Tianeptine Citalopram Dose order: Placebo, Citalopram, Tianeptine Placebo, Citalopram, Tianeptine Tianeptine Dose order: Placebo, Citalopram, Tianeptine Placebo, Tianeptine, Citalopram Citalopram Dose order: Placebo, Tianeptine, Citalopram Placebo, Tianeptine, Citalopram Tianeptine Dose order: Placebo, Tianeptine, Citalopram Citalopram, Placebo, Tianeptine Citalopram Dose order: Citalopram, Placebo, Tianeptine Tianeptine, Citalopram, Placebo Tianeptine Dose order: Tianeptine, Citalopram, Placebo Citalopram, Placebo, Tianeptine Tianeptine Dose order: Citalopram, Placebo, Tianeptine Citalopram, Tianeptine, Placebo Citalopram Dose order: Citalopram, Tianeptine, Placebo Citalopram, Tianeptine, Placebo Tianeptine Dose order: Citalopram, Tianeptine, Placebo Tianeptine, Placebo, Citalopram Citalopram Dose order: Tianeptine, Placebo, Citalopram Tianeptine, Placebo, Citalopram Tianeptine Dose order: Tianeptine, Placebo, Citalopram Tianeptine, Citalopram, Placebo Citalopram Dose order: Tianeptine, Citalopram, Placebo
- Primary Outcome Measures
Name Time Method Brain excitation and inhibition response to pharmacological stimulation as assessed by magnetic resonance spectroscopy 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 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 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.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
King's College London
š¬š§London, United Kingdom