HealthyCOMBI-STIMNCT03056170
Neurophysiological Impact of a Fronto-temporal tDCS Stimulation in Healthy Subjects: a Multimodal Imaging Approach
A study testing real tDCS in people with Healthy, run by Hospices Civils de Lyon at 1 site in France.
Trial summary
tDCS is a technique emerging as a prospective therapy for neurologic, psychiatric and addictive disorders. Specifically, fronto-temporal tDCS, with anodal stimulation over the left dorsolateral prefrontal cortex (DLPFC) and cathodal stimulation over the left temporo-parietal junction (TPJ), has been reported to reduce… Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- real tDCS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 37 participants
- Where
- 1 siteFrance
- Study dates
- 13 Nov 2015to 20 Jun 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- non smoker
- right handed
- non psychotropic consumption
- no medical treatment except oral contraception
- no psychiatric or somatic (neurological, endocrine, cardiac, renal) disorders
- affiliated to the French social security
Who cannot join
- No Consent formed signed
- For female participants : pregnancy
- contraindications to stimulation by tDCS or to an MRI exam
- being in an exclusion period or over the annual compensation threshold
- participation in another study using ionizing radiation in less than a year
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Neurophysiological Impact of a Fronto-temporal Transcranial Direct Current Stimulation (tDCS) in Healthy Subjects: a Multimodal Imaging Approach
tDCS is a technique emerging as a prospective therapy for neurologic, psychiatric and addictive disorders. Specifically, fronto-temporal tDCS, with anodal stimulation over the left dorsolateral prefrontal cortex (DLPFC) and cathodal stimulation over the left temporo-parietal junction (TPJ), has been reported to reduce treatment-resistant auditory hallucinations (AH), negative symptoms and insight of the illness in schizophrenia. However, despite an increasing use in clinical settings, tDCS suffers from limitations, especially regarding the strength and the duration of therapeutic effects.
Some imaging reports suggest that tDCS effects are not restricted to the brain areas located under the electrodes, but spread through distributed cortical networks functionally connected with the targets and reach subcortical areas. Overall, these studies suggest that tDCS modulates functional connectivity within and across resting-state networks and brain activity. However, these effects are currently described at different levels depending on the imaging technique used. Moreover, the majority of studies have focused on motor cortex stimulation, while the specific effects of fronto-temporal tDCS are scarce. Finally, effects of the stimulation applied online are rarely inspected.
Read more
According to the therapeutic effects of fronto-temporal tDCS on schizophrenia and the dopaminergic pathophysiological hypothesis of schizophrenia, the effect of fronto-temporal tDCS on dopaminergic transmission is of major interest. As the cortex is densely connected with basal ganglia areas, tDCS effects are probably capable to reach subcortical dopaminergic areas. Indeed, recent fMRI studies highlighted subcortical effects of tDCS applied at the cortical level including modulations of cortico-striatal and thalamo-cortical functional connectivity. In addition, some studies suggest that cortical stimulation by other approaches, such as transcranial magnetic stimulation (rTMS) modulates dopaminergic transmission. However, tDCS effects on dopaminergic transmission have been investigated only indirectly.
Finally, information about biological effects of tDCS is scattered and creating a coherent ensemble is a mandatory and critical step to understand the mechanisms of action of tDCS.
According to the hypothesis that fronto-temporal tDCS modulates brain activity, connectivity and dopaminergic transmission, the aim of this project is to reveal the combined neurobiological impact of an online single session of fronto-temporal tDCS in a unique experiment by developing a simultaneous multimodal imaging approach (PET-MRI). The online implementation of the stimulation will allow deciphering changes induced during and after stimulation. As a first step before investigating patients with schizophrenia, healthy subjects will be involved in the present study.
The distributed changes will be explored at rest through:
- Spontaneous functional connectivity assessed by functional magnetic resonance imagery (fMRI).
- Brain activity assessed by cerebral blood flow quantitatively and directly measured by arterial spin labelling (ASL).
- Connectivity assessed by diffusion tensor imaging (DTI).
- Specific and localized dopaminergic transmission evaluated by positron emission tomography (PET) using dopaminergic D2 subtype receptor availability via [11C]raclopride binding.
The pioneering aspects of the project are to use an innovative simultaneous multimodal imaging system, adopt the tDCS montage used in our validated therapeutic context and apply tDCS online. We expect that our unique approach will provide an imaging biomarker essential to improve our understanding of:
- the "normal brain" and further deficient mechanisms underlying schizophrenia as well as neurological disorders.
- neurobiological effects of tDCS in order to:
- Bring key element of the proof of concept of tDCS
- Optimize tDCS in a therapeutic context
- Suggest a marker of the therapeutic response
- Conditions
- Healthy
- Being tested
- real tDCS
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
real tDCSDevice
In active stimulation, the "Transcranial Direct Current Stimulation" device will produce a direct current of 1 mA from one electrode to the other for 30 min with a ramp up at the beginning and a ramp down at the end of the stimulation of 30 s. The sham or active mode is chosen by a numeric code.
| Study group | Role | What they receive |
|---|---|---|
| Active tDCS | Active comparator | The anode is placed over the left dorsolateral prefrontal cortex (DLPFC) and the cathode is placed over the left temporo-parietal cortex (TPJ) In active stimulation with a Transcranial Direct Current Stimulation, the device will deliver a charge of 1 mA for 30 minutes. Receives: Device: real tDCS |
| Sham tDCS | Sham comparator | In sham stimulation, with a Transcranial Direct Current Stimulation, no current will be delivered from one electrode to the other except one 30 s ramp up and down at the beginning and one at the end of the sham stimulation duration (30 min) Same electrode montage than in the active group. Receives: Device: real tDCS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in dopamine transmission induced by 1 session of 30min tDCS
Measure of the Binding Ratio of the radiomarker defined as the ratio of : region of interest / cerebellum activities
Measured: Continuous measure during 110min of PET scan
Secondary outcomes (3)
Change in spontaneous functional connectivity (using rs fMRI) during and after 1 session of 30min tDCS
The impact of tDCS will be analysed using functional connectivity maps seeded from stimulated regions and from areas belonging to specific networks. Data will be preprocessed and analyzed using specific toolbox.
Measured: - Before stimulation : t+15 to t+28min - During stimulation : t+45 to t+58min - After stimulation : t+76 to t+89min
Change in cerebral blood flow (using ASL) during and after 1 session of 30min tDCS
The impact of tDCS will be analysed using quantitative CBF maps seeded from stimulated regions and from areas belonging to specific networks. Data will be preprocessed and analyzed using specific toolbox.
Measured: - Before stimulation : t+30 to t+36min - During stimulation : t+60 to t+66min - After stimulation : t+91 to t+97min
Change in structural connectivity (using DTI) after 1 session of 30min tDCS
The impact of tDCS will be analysed using a tractography-based analysis. Data will be preprocessed and analyzed using specific toolbox.
Measured: - Before stimulation : t+0 to t+10min - After stimulation : t+100 to t+110min
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2017
- Study start13 Nov 2015
- Primary completion19 Apr 2017
- Study completion20 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Frédéric Haesebaert, MD, Principal investigator, LE VINATIER
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03056170
- Sponsor's protocol ID
- 69HCL16_0682
- Acronym
- COMBI-STIM
- Status last verified
- Sep 2025
- First submitted
- 8 Feb 2017
- Last updated
- 25 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Fonteneau C, Merida I, Redoute J, Haesebaert F, Lancelot S, Costes N, Mondino M, Brunelin J. Modulation of dopaminergic transmission and brain activity by frontotemporal tDCS: A multimodal PET-MR imaging study. Brain Stimul. 2025 Jul-Aug;18(4):1065-1073. doi: 10.1016/j.brs.2025.05.006. Epub 2025 May 6.
PubMed 40340023
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neurophysiological Impact of a Fronto-temporal Transcranial Direct Current Stimulation (tDCS) in Healthy Subjects: a Multimodal Imaging Approach
- ClinicalTrials.gov ID
- NCT03056170
- Acronym / sponsor ID
- COMBI-STIM / 69HCL16_0682
- Conditions
- Healthy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 13 Nov 2015 (actual)
- Primary completion
- 19 Apr 2017 (actual)
- Study completion
- 20 Jun 2017 (actual)
- First posted
- 17 Feb 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
tDCS is a technique emerging as a prospective therapy for neurologic, psychiatric and addictive disorders. Specifically, fronto-temporal tDCS, with anodal stimulation over the left dorsolateral prefrontal cortex (DLPFC) and cathodal stimulation over the left temporo-parietal junction (TPJ), has been reported to reduce treatment-resistant auditory hallucinations (AH), negative symptoms and insight of the illness in schizophrenia. However, despite an increasing use in clinical settings, tDCS suffers from limitations, especially regarding the strength and the duration of therapeutic effects.
Some imaging reports suggest that tDCS effects are not restricted to the brain areas located under the electrodes, but spread through distributed cortical networks functionally connected with the targets and reach subcortical areas. Overall, these studies suggest that tDCS modulates functional connectivity within and across resting-state networks and brain activity. However, these effects are currently described at different levels depending on the imaging technique used. Moreover, the majority of studies have focused on motor cortex stimulation, while the specific effects of fronto-temporal tDCS are scarce. Finally, effects of the stimulation applied online are rarely inspected.
According to the therapeutic effects of fronto-temporal tDCS on schizophrenia and the dopaminergic pathophysiological hypothesis of schizophrenia, the effect of fronto-temporal tDCS on dopaminergic transmission is of major interest. As the cortex is densely connected with basal ganglia areas, tDCS effects are probably capable to reach subcortical dopaminergic areas. Indeed, recent fMRI studies highlighted subcortical effects of tDCS applied at the cortical level including modulations of cortico-striatal and thalamo-cortical functional connectivity. In addition, some studies suggest that cortical stimulation by other approaches, such as transcranial magnetic stimulation (rTMS) modulates dopaminergic transmission. However, tDCS effects on dopaminergic transmission have been investigated only indirectly.
Finally, information about biological effects of tDCS is scattered and creating a coherent ensemble is a mandatory and critical step to understand the mechanisms of action of tDCS.
According to the hypothesis that fronto-temporal tDCS modulates brain activity, connectivity and dopaminergic transmission, the aim of this project is to reveal the combined neurobiological impact of an online single session of fronto-temporal tDCS in a unique experiment by developing a simultaneous multimodal imaging approach (PET-MRI). The online implementation of the stimulation will allow deciphering changes induced during and after stimulation. As a first step before investigating patients with schizophrenia, healthy subjects will be involved in the present study.
The distributed changes will be explored at rest through:
- Spontaneous functional connectivity assessed by functional magnetic resonance imagery (fMRI).
- Brain activity assessed by cerebral blood flow quantitatively and directly measured by arterial spin labelling (ASL).
- Connectivity assessed by diffusion tensor imaging (DTI).
- Specific and localized dopaminergic transmission evaluated by positron emission tomography (PET) using dopaminergic D2 subtype receptor availability via [11C]raclopride binding.
The pioneering aspects of the project are to use an innovative simultaneous multimodal imaging system, adopt the tDCS montage used in our validated therapeutic context and apply tDCS online. We expect that our unique approach will provide an imaging biomarker essential to improve our understanding of:
- the "normal brain" and further deficient mechanisms underlying schizophrenia as well as neurological disorders.
- neurobiological effects of tDCS in order to:
- Bring key element of the proof of concept of tDCS
- Optimize tDCS in a therapeutic context
- Suggest a marker of the therapeutic response
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active tDCS | Active comparator | Device: real tDCSThe anode is placed over the left dorsolateral prefrontal cortex (DLPFC) and the cathode is placed over the left temporo-parietal cortex (TPJ) In active stimulation with a Transcranial Direct Current Stimulation, the device will deliver a charge of 1 mA for 30 minutes. |
| Sham tDCS | Sham comparator | Device: real tDCSIn sham stimulation, with a Transcranial Direct Current Stimulation, no current will be delivered from one electrode to the other except one 30 s ramp up and down at the beginning and one at the end of the sham stimulation duration (30 min) Same electrode montage than in the active group. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- non smoker
- right handed
- non psychotropic consumption
- no medical treatment except oral contraception
- no psychiatric or somatic (neurological, endocrine, cardiac, renal) disorders
Key exclusion criteria (5 listed)
- No Consent formed signed
- For female participants : pregnancy
- contraindications to stimulation by tDCS or to an MRI exam
- being in an exclusion period or over the annual compensation threshold
- participation in another study using ionizing radiation in less than a year
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| real tDCSIn active stimulation, the "Transcranial Direct Current Stimulation" device will produce a direct current of 1 mA from one electrode to the other for 30 min with a ramp up at the beginning and a ramp down at the end of the stimulation of 30 s. The sham or active mode is chosen by a numeric code. | Device | Active tDCS, Sham tDCS |
Primary outcome
Change in dopamine transmission induced by 1 session of 30min tDCS
Time frame: Continuous measure during 110min of PET scan
Measure of the Binding Ratio of the radiomarker defined as the ratio of : region of interest / cerebellum activities
3 secondary outcomes
Change in spontaneous functional connectivity (using rs fMRI) during and after 1 session of 30min tDCS
Time frame: - Before stimulation : t+15 to t+28min - During stimulation : t+45 to t+58min - After stimulation : t+76 to t+89min
Change in cerebral blood flow (using ASL) during and after 1 session of 30min tDCS
Time frame: - Before stimulation : t+30 to t+36min - During stimulation : t+60 to t+66min - After stimulation : t+91 to t+97min
Change in structural connectivity (using DTI) after 1 session of 30min tDCS
Time frame: - Before stimulation : t+0 to t+10min - After stimulation : t+100 to t+110min
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2025.
- Results publication: PubMed 40340023Fonteneau C, Merida I, Redoute J, Haesebaert F, Lancelot S, Costes N, Mondino M, Brunelin J. Modulation of dopaminergic transmission and brain activity by frontotemporal tDCS: A multimodal PET-MR imaging study. Brain Stimul. 2025 Jul-Aug;18(4):1065-1073. doi: 10.1016/j.brs.2025.05.006. Epub 2025 May 6.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Frédéric Haesebaert, MD principal investigator
LE VINATIER
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing real tDCS in people with Healthy, run by Hospices Civils de Lyon at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in dopamine transmission induced by 1 session of 30min tDCS (time frame: Continuous measure during 110min of PET scan). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03056170, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2025.