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

Sponsor

Hôpital le Vinatier (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05825677

Collaborator

(none)

Enrollment

Arms

24.5

Anticipated Duration (Months)

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Stress Response	Device: tDCS actif Device: tDCS Sham	N/A

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

In a randomized controlled double-blind study, 30 healthy subjects, will be randomly assigned to 2 groups. A group of 15 participants will receive 30 minutes of active tDCS (1mA, 30 minutes with the anode at the left DLPFC and the cathode at the right DLPFC); a group of 15 participants will receive 30 minutes of placebo stimulation. All participant will be in a PET-MRI scanner for 110min, during which they will undergo the stimulation (either active or sham). During this stimulation session, all participants will undergo a standardized stress test combining psychosocial stress and physical stress.In a randomized controlled double-blind study, 30 healthy subjects, will be randomly assigned to 2 groups. A group of 15 participants will receive 30 minutes of active tDCS (1mA, 30 minutes with the anode at the left DLPFC and the cathode at the right DLPFC); a group of 15 participants will receive 30 minutes of placebo stimulation. All participant will be in a PET-MRI scanner for 110min, during which they will undergo the stimulation (either active or sham). During this stimulation session, all participants will undergo a standardized stress test combining psychosocial stress and physical stress.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

The subject will be blind of the treatment he receives (active or placebo). The experimenter, caregiver and investigator will also be blinded from stimulation (active or placebo). Each subject will be assigned a randomization code, corresponding to the code to enter the tDCS device. This system allows the person who administers tDCS and the subject receiving the stimulation to be blind.

Primary Purpose:

Basic Science

Official Title:

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

Anticipated Study Start Date :

Apr 15, 2023

Anticipated Primary Completion Date :

Apr 15, 2024

Anticipated Study Completion Date :

Apr 30, 2025

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Active tDCS Active brain stimulation Direct current stimulation of DLPFC for 30min with an intensity of 1mA	Device: tDCS actif Active brain stimulation
Sham Comparator: Sham tDCS Sham brain stimulation Direct current stimulation of DLPFC for 30sec with an intensity of 1mA	Device: tDCS Sham Sham brain stimulation

Arm

Intervention/Treatment

Active Comparator: Active tDCS

Active brain stimulation Direct current stimulation of DLPFC for 30min with an intensity of 1mA

Device: tDCS actif

Active brain stimulation

Sham Comparator: Sham tDCS

Sham brain stimulation Direct current stimulation of DLPFC for 30sec with an intensity of 1mA

Device: tDCS Sham

Sham brain stimulation

Outcome Measures

Primary Outcome Measures

Dopamine transmission measured with positron emission tomography [One year]
Subcortical dopaminergic transmission will be analyzed, using [11C]raclopride PET activity (D2 receptor antagonist)

Secondary Outcome Measures

Functional brain connectivity [One year]
Resting-state functional connectivity
Hormonal stress reactivity [One year]
ACTH level will be measured
Cognitive stress reactivity [One year]
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.
Expression of genes involved in the glucocorticoid receptor signaling pathway measured through blood samples [One year]
Expression rates of genes involved in the glucocorticoid receptor signaling pathway
Assessment of brain-derived neurotrophic factor before and after transcranial direct current stimulation. [One year]
Exploratory measure: brain-derived neurotrophic factor polymorphisms of participants, involved in differential Transcranial direct current stimulation response, will be assess.
Hormonal stress reactivity [One year]
Cortisol level will be measured
Assessment of Cytoplasmic catechol-O-methyltransferase polymorphisms before and after transcranial direct current stimulation. [One year]
Exploratory measure: Cytoplasmic catechol-O-methyltransferase polymorphisms of participants, involved in differential Transcranial direct current stimulation response, will be assess.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 30 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Hôpital le Vinatier

Investigators

Study Director: Jérôme BRUNELIN, PhD, Vinatier Hospital PsyR2 Team

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Hôpital le Vinatier

ClinicalTrials.gov Identifier:

NCT05825677

Other Study ID Numbers:

2022-A00907-36

First Posted:

Apr 24, 2023

Last Update Posted:

Apr 24, 2023

Last Verified:

Apr 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Study Results

No Results Posted as of Apr 24, 2023