Brain Response to Serotonergic Medications in ASD

Sponsor
King's College London (Other)
Overall Status
Recruiting
CT.gov ID
NCT04145076
Collaborator
(none)
100
1
6
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Study Details

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.

Condition or Disease Intervention/Treatment Phase
N/A

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
100 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Intervention Model Description:
Repeated-measures cross-over study, where each subject receives each of three pharmacological probes once (order of drug administration was pseudorandomised).Repeated-measures cross-over study, where each subject receives each of three pharmacological probes once (order of drug administration was pseudorandomised).
Masking:
Double (Participant, Investigator)
Masking Description:
Participants and investigators are blinded to the drug condition.
Primary Purpose:
Basic Science
Official Title:
Can Brain Activation and Connectivity Predict Treatment Response to Two Serotonergic Medications (Citalopram and Tianeptine) in Subjects With Autism Spectrum Disorders (ASD)?
Actual Study Start Date :
Dec 15, 2014
Anticipated Primary Completion Date :
Feb 1, 2023
Anticipated Study Completion Date :
May 31, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Placebo, Citalopram, Tianeptine

Dose order: Placebo, Citalopram, Tianeptine

Drug: Placebo
Two oral doses of placebo.

Drug: Citalopram
Single oral dose of citalopram (20mg) and single oral dose of placebo.

Drug: Tianeptine
Single oral dose of tianeptine (12.5mg) and single oral dose of placebo.

Experimental: Placebo, Tianeptine, Citalopram

Dose order: Placebo, Tianeptine, Citalopram

Drug: Placebo
Two oral doses of placebo.

Drug: Citalopram
Single oral dose of citalopram (20mg) and single oral dose of placebo.

Drug: Tianeptine
Single oral dose of tianeptine (12.5mg) and single oral dose of placebo.

Experimental: Citalopram, Placebo, Tianeptine

Dose order: Citalopram, Placebo, Tianeptine

Drug: Placebo
Two oral doses of placebo.

Drug: Citalopram
Single oral dose of citalopram (20mg) and single oral dose of placebo.

Drug: Tianeptine
Single oral dose of tianeptine (12.5mg) and single oral dose of placebo.

Experimental: Citalopram, Tianeptine, Placebo

Dose order: Citalopram, Tianeptine, Placebo

Drug: Placebo
Two oral doses of placebo.

Drug: Citalopram
Single oral dose of citalopram (20mg) and single oral dose of placebo.

Drug: Tianeptine
Single oral dose of tianeptine (12.5mg) and single oral dose of placebo.

Experimental: Tianeptine, Placebo, Citalopram

Dose order: Tianeptine, Placebo, Citalopram

Drug: Placebo
Two oral doses of placebo.

Drug: Citalopram
Single oral dose of citalopram (20mg) and single oral dose of placebo.

Drug: Tianeptine
Single oral dose of tianeptine (12.5mg) and single oral dose of placebo.

Experimental: Tianeptine, Citalopram, Placebo

Dose order: Tianeptine, Citalopram, Placebo

Drug: Placebo
Two oral doses of placebo.

Drug: Citalopram
Single oral dose of citalopram (20mg) and single oral dose of placebo.

Drug: Tianeptine
Single oral dose of tianeptine (12.5mg) and single oral dose of placebo.

Outcome Measures

Primary Outcome Measures

  1. 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.

  2. 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.

  3. 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 60 Years
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
Yes
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 King's College London London United Kingdom SE5 8AF

Sponsors and Collaborators

  • King's College London

Investigators

  • Principal Investigator: Grainne McAlonan, PhD, King's College London
  • Study Chair: Declan Murphy, PhD, King's College London

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Dr Grainne McAlonan, Deputy head of department, King's College London
ClinicalTrials.gov Identifier:
NCT04145076
Other Study ID Numbers:
  • 14/LO/0663
First Posted:
Oct 30, 2019
Last Update Posted:
Apr 15, 2022
Last Verified:
Apr 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Dr Grainne McAlonan, Deputy head of department, King's College London
Additional relevant MeSH terms:

Study Results

No Results Posted as of Apr 15, 2022