Clinical trial NCT04145076: Brain Response to Serotonergic Medications in ASD
Official title: Can Brain Activation and Connectivity Predict Treatment Response to Two Serotonergic Medications (Citalopram and Tianeptine) in Subjects With Autism Spectrum Disorders (ASD)?
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Autism Spectrum Disorder
Keywords: citalopram
tianeptine
pharmacological imaging
Lead sponsor: King's College London
Sponsor class: OTHER
First posted: 2019-10-30
Enrollment: 100
Sex: MALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Repeated-measures cross-over study, where each subject receives each of three pharmacological probes once (order of drug administration was pseudorandomised).
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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

Primary outcomes:
measure: Brain excitation and inhibition response to pharmacological stimulation as assessed by magnetic resonance spectroscopy
timeFrame: In the months 1-2 following the last day of scanning
measure: Brain activation response to pharmacological stimulation as assessed by functional magnetic resonance imaging
timeFrame: In the months 3-4 following the last day of scanning
measure: Brain connectivity response to pharmacological stimulation as assessed by resting-state functional magnetic resonance imaging
timeFrame: In the months 5-6 following the last day of scanning
Secondary outcomes:
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: King's College London
Study officials:
affiliation: King's College London
name: Grainne McAlonan, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: King's College London
name: Declan Murphy, PhD
role: STUDY_CHAIR
References: