Investigating Stress-Induced Dopamine Release: a fMRI-PET Study

Stress Response Clinical Trial

— ISIDORE  

Official title:

Investigating Stress-Induced Dopamine Release: a fMRI-PET Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05825677
• Other study ID #: 2022-A00907-36
• Status: Recruiting
• Phase: N/A
• Start date: April 11, 2023
• Est. completion date: April 30, 2025

Study information

• Verified date: May 2023
• Source: Hôpital le Vinatier
• Contact: Frédéric HAESEBAERT, MD - PhD
• Phone: 0033437915565
• Email: Frederic.HAESEBAERT[@]ch-le-vinatier.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The stress response is mediated by the activation of the hypothalamo-pituitary-adrenal axis and the sympathetic nervous system, leading to glucocorticoid and catecholamines release respectively. This stress response is regulated by feedback loops, involving cortical and subcortical structures.

Non-invasive brain stimulation applied over the dorsolateral prefrontal cortex modulates the subcortical dopaminergic transmission at rest and can reduce the hormonal and cognitive alterations induced by stress. This study aims to investigate the Non-invasive brain stimulation -induced modulation of dopamine transmission in an acute stress situation.

Description:

Objective: to investigate the influence of Dorsolateral Prefrontal Cortex stimulation during acute stress on the subcortical dopamine transmission in healthy subjects.

Method: 30 healthy subjects will be enrolled and randomized into 2 parallel groups. 15 participants will receive active Transcranial direct current stimulation , the other 15 participants will receive sham Transcranial direct current stimulation.

Transcranial direct current stimulation procedure: active Transcranial direct current stimulation corresponds to 30min of stimulation at 1mA intensity . The sham stimulation corresponds to 30s of real stimulation.

Stress paradigm: In order to induce moderate stress in humans in laboratory condition, the investigators will use the Maastricht Acute Stress test . This test is a combination between physical, hand immersion in cold water and cognitive calculation stress. The test will start 5 minutes after the beginning of stimulation session.

Stress measures: the stress response will be evaluated at the following levels:

• Neurochemical level: dopamine transmission measured with positron emission tomography

• Functional brain connectivity: resting-state networks measured with functional magnetic resonance imaging

• Hormonal level: adrenocorticotropic hormone and cortisol levels measured with blood samples

• Cognitive level: decision-making and memory assessed with delay-discounting task and reality-monitoring task, respectively

• Molecular level: expression of genes involved in the glucocorticoid receptor signaling pathway measured through blood samples Exploratory measure: Brain-Derived Neurotrophic Factor and cytoplasmic catechol-O-methyltransferase polymorphisms of participants involved in differential Transcranial direct current stimulation response will be assessed.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: April 30, 2025
• Est. primary completion date: April 15, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 30 Years

Eligibility

Inclusion Criteria:

• - Men and women aged between 18- and 30-year-old

• Non-smoker

• Non-psychotropic user

Exclusion Criteria:

• - Have a psychiatric or somatic disorder

• Have a first-degree family history of a psychiatric disorder

• Pregnant or nursing women

• Be on medication, with the exception of oral contraceptives

• Contraindications to tDCS or MRI examination

• Participants with pacemaker or cardiac or cerebral implant

Related Conditions & MeSH terms

• Stress Response

Intervention

Device:
• tDCS actif
Active brain stimulation
• tDCS Sham
Sham brain stimulation

Locations

Country	Name	City	State
France	Ch Le Vinatier	Lyon	Rhone Alpes

Sponsors (1)

Lead Sponsor	Collaborator
Hôpital le Vinatier

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dopamine transmission measured with positron emission tomography	Subcortical dopaminergic transmission will be analyzed, using [11C]raclopride PET activity (D2 receptor antagonist)	One year
Secondary	Functional brain connectivity	Resting-state functional connectivity	One year
Secondary	Hormonal stress reactivity	ACTH level will be measured	One year
Secondary	Cognitive stress reactivity	Decision-making capacities will be measured using a computerized version of the DDT in which participants have to choose between 2 rewards. Memory capacities will be measured using a computerized task evaluating reality-memory.	One year
Secondary	Expression of genes involved in the glucocorticoid receptor signaling pathway measured through blood samples	Expression rates of genes involved in the glucocorticoid receptor signaling pathway	One year
Secondary	Assessment of brain-derived neurotrophic factor before and after transcranial direct current stimulation.	Exploratory measure: brain-derived neurotrophic factor polymorphisms of participants, involved in differential Transcranial direct current stimulation response, will be assess.	One year
Secondary	Hormonal stress reactivity	Cortisol level will be measured	One year
Secondary	Assessment of Cytoplasmic catechol-O-methyltransferase polymorphisms before and after transcranial direct current stimulation.	Exploratory measure: Cytoplasmic catechol-O-methyltransferase polymorphisms of participants, involved in differential Transcranial direct current stimulation response, will be assess.	One year