Back to resultsBrain Response to Serotonergic Medications in ASD
Primary Purpose
Autism Spectrum Disorder
Status
Recruiting
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Placebo
Citalopram
Tianeptine
Sponsored by
About this trial
This is an interventional basic science trial for Autism Spectrum Disorder focused on measuring citalopram, tianeptine, pharmacological imaging
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
Sites / Locations
- King's College LondonRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Placebo, Citalopram, Tianeptine
Placebo, Tianeptine, Citalopram
Citalopram, Placebo, Tianeptine
Citalopram, Tianeptine, Placebo
Tianeptine, Placebo, Citalopram
Tianeptine, Citalopram, Placebo
Arm Description
Dose order: Placebo, Citalopram, Tianeptine
Dose order: Placebo, Tianeptine, Citalopram
Dose order: Citalopram, Placebo, Tianeptine
Dose order: Citalopram, Tianeptine, Placebo
Dose order: Tianeptine, Placebo, Citalopram
Dose order: Tianeptine, Citalopram, Placebo
Outcomes
Primary Outcome Measures
Brain excitation and inhibition response to pharmacological stimulation as assessed by magnetic resonance spectroscopy
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
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
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04145076
Brief Title
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
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Recruiting
Study Start Date
December 15, 2014 (Actual)
Primary Completion Date
February 2023 (Anticipated)
Study Completion Date
May 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
King's College London
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autism Spectrum Disorder
Keywords
citalopram, tianeptine, pharmacological imaging
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Model Description
Repeated-measures cross-over study, where each subject receives each of three pharmacological probes once (order of drug administration was pseudorandomised).
Masking
ParticipantInvestigator
Masking Description
Participants and investigators are blinded to the drug condition.
Allocation
Randomized
Enrollment
100 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Placebo, Citalopram, Tianeptine
Arm Type
Experimental
Arm Description
Dose order: Placebo, Citalopram, Tianeptine
Arm Title
Placebo, Tianeptine, Citalopram
Arm Type
Experimental
Arm Description
Dose order: Placebo, Tianeptine, Citalopram
Arm Title
Citalopram, Placebo, Tianeptine
Arm Type
Experimental
Arm Description
Dose order: Citalopram, Placebo, Tianeptine
Arm Title
Citalopram, Tianeptine, Placebo
Arm Type
Experimental
Arm Description
Dose order: Citalopram, Tianeptine, Placebo
Arm Title
Tianeptine, Placebo, Citalopram
Arm Type
Experimental
Arm Description
Dose order: Tianeptine, Placebo, Citalopram
Arm Title
Tianeptine, Citalopram, Placebo
Arm Type
Experimental
Arm Description
Dose order: Tianeptine, Citalopram, Placebo
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Two oral doses of placebo.
Intervention Type
Drug
Intervention Name(s)
Citalopram
Intervention Description
Single oral dose of citalopram (20mg) and single oral dose of placebo.
Intervention Type
Drug
Intervention Name(s)
Tianeptine
Intervention Description
Single oral dose of tianeptine (12.5mg) and single oral dose of placebo.
Primary Outcome Measure Information:
Title
Brain excitation and inhibition response to pharmacological stimulation as assessed by magnetic resonance spectroscopy
Description
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.
Time Frame
In the months 1-2 following the last day of scanning
Title
Brain activation response to pharmacological stimulation as assessed by functional magnetic resonance imaging
Description
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.
Time Frame
In the months 3-4 following the last day of scanning
Title
Brain connectivity response to pharmacological stimulation as assessed by resting-state functional magnetic resonance imaging
Description
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.
Time Frame
In the months 5-6 following the last day of scanning
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nichol Wong, PhD
Phone
+44 (0)2078480124
Email
nichol.wong@kcl.ac.uk
First Name & Middle Initial & Last Name or Official Title & Degree
Grainne McAlonan, PhD
Phone
+44 (0)2078480831
Email
grainne.mcalonan@kcl.ac.uk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Grainne McAlonan, PhD
Organizational Affiliation
King's College London
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Declan Murphy, PhD
Organizational Affiliation
King's College London
Official's Role
Study Chair
Facility Information:
Facility Name
King's College London
City
London
ZIP/Postal Code
SE5 8AF
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nichol Wong, PhD
Phone
+44 (0)2078480124
Email
nichol.wong@kcl.ac.uk
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Brain Response to Serotonergic Medications in ASD
We'll reach out to this number within 24 hrs