Brain Response to Serotonergic Medications in ASD

NCT ID: NCT04145076

Last Updated: 2022-04-15

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-15
• Study Completion Date: 2023-05-31

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.

Conditions

Autism Spectrum Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Placebo, Citalopram, Tianeptine

Dose order: Placebo, Citalopram, Tianeptine

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Two oral doses of placebo.

Citalopram

Intervention Type: DRUG

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

Tianeptine

Intervention Type: DRUG

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

Placebo, Tianeptine, Citalopram

Dose order: Placebo, Tianeptine, Citalopram

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Two oral doses of placebo.

Citalopram

Intervention Type: DRUG

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

Tianeptine

Intervention Type: DRUG

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

Citalopram, Placebo, Tianeptine

Dose order: Citalopram, Placebo, Tianeptine

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Two oral doses of placebo.

Citalopram

Intervention Type: DRUG

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

Tianeptine

Intervention Type: DRUG

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

Citalopram, Tianeptine, Placebo

Dose order: Citalopram, Tianeptine, Placebo

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Two oral doses of placebo.

Citalopram

Intervention Type: DRUG

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

Tianeptine

Intervention Type: DRUG

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

Tianeptine, Placebo, Citalopram

Dose order: Tianeptine, Placebo, Citalopram

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Two oral doses of placebo.

Citalopram

Intervention Type: DRUG

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

Tianeptine

Intervention Type: DRUG

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

Tianeptine, Citalopram, Placebo

Dose order: Tianeptine, Citalopram, Placebo

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Two oral doses of placebo.

Citalopram

Intervention Type: DRUG

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

Tianeptine

Intervention Type: DRUG

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

Interventions

Placebo

Two oral doses of placebo.

Intervention Type: DRUG

Citalopram

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

Intervention Type: DRUG

Tianeptine

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

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

King's College London

OTHER

Sponsor Role: lead

Responsible Party

Dr Grainne McAlonan

Deputy head of department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Grainne McAlonan, PhD

Role: PRINCIPAL_INVESTIGATOR

King's College London

Declan Murphy, PhD

Role: STUDY_CHAIR

King's College London

Locations

King's College London

London, , United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Central Contacts

Nichol Wong, PhD

Role: CONTACT

nichol.wong@kcl.ac.uk

+44 (0)2078480124

Grainne McAlonan, PhD

Role: CONTACT

grainne.mcalonan@kcl.ac.uk

+44 (0)2078480831

Facility Contacts

Nichol Wong, PhD

Role: primary

nichol.wong@kcl.ac.uk

+44 (0)2078480124

Other Identifiers

14/LO/0663

Identifier Type: -

Identifier Source: org_study_id