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Depressive Disorder, MajorDEPSTIMNCT05121129

Treatment of Major Depression by rTMS on Dorsolateral Prefrontal Cortex: Study of Underlying Mechanisms

A study testing iTBS in people with Depressive Disorder, Major, run by Centre Hospitalier Universitaire de Besancon at 1 site in France.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The study aims to evaluate the impact of repeated Transcranial Magnetic Stimulation (rTMS) on underlying neuronal mechanisms of adults suffering from major depression disorder (MDD). Read more about this study

Who is it for?
Ages 35 to 65 years
Conditions the study is for
Depressive Disorder, Major
What is being tested?
iTBS
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteFrance
Study dates
13 Oct 2021to 9 Apr 2023
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 35 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of MDD (Diagnostic and Statistical Manual of Mental Disorders V [DSM-V] and (Mini International Neuropsychiatric Interview [MINI] criteria, QIDS-C16≥18)
  • Right-handed
  • No response at a first antidepressant
  • Under AD ≥ 6 weeks
  • No contraindications for rTMS and MRI
  • Absence of addictive comorbidities
Show all 10Show fewer
  • Absence of severe progressive neurologic and/or somatic pathologies (specially tumors, neurodegenerative diseases)
  • Inpatients or outpatients of Adult Psychiatric Department
  • Signed informed consent form
  • Subjects affiliated to or beneficiary from a French social security regime

Who cannot join

  • Subjects under 35 years old or over 65 years old
  • Treated with over 4 AD for the current episode
  • ECT or rTMS for current episode
  • BZD or antiepileptic (except pregabalin up to 75 mg / d, zopiclone ≤7.5 mg / d)
  • Left-handed
  • Subject under measure of protection or guardianship of justice
Show all 12Show fewer
  • Presence of psychiatric comorbidities
  • Subject beneficiary from a legal protection regime
  • Subject unlikely to cooperate or low cooperation stated by investigator
  • Subject not covered by social security
  • Pregnant woman
  • Subject being in the exclusion period of another study or provided for by the "National Volunteer File

Trial locations and contacts

1 site in 1 country.

Emmanuel HAFFEN, Professor contact

+33381218154

emmanuel.haffen@univ-fcomte.fr

magali nicolier, PhD contact

+33381219007

mnicolier@chu-besancon.fr

France1 site, 1 recruiting
  • Magali NICOLIER

    Besançon, 25030

    Magali NICOLIER, PhD, +33381219007, mnicolier@chu-besancon.fr

    Emmanuel HAFFEN, MD PhD

    Recruiting

Other trials in France

About this study

Official title: Treatment of Major Depression by Magnetic Stimulation Repeated Transcranial on Prefrontal Cortex: Study of Underlying Mechanisms

The study aims to evaluate the impact of repeated Transcranial Magnetic Stimulation (rTMS) on underlying neuronal mechanisms of adults suffering from major depression disorder (MDD). Short- and long-term effects are assessed by High-Resolution electroencephalography (HR-EEG) or Magnetic Resonance Imaging (MRI) records, experimental tasks and self-rated scales.

Read the detailed description

Depression is associated with functional and structural changes in the brain, notably in DLPFC (DorsoLateral PreFrontal Cortex). High-frequency rTMS (10 Hz) applied to the left DLPFC is associated with a response rate 3.75 times and remission 2.52 higher than placebo for the treatment of MDD with more reproducible results than those observed for the others rTMS stimulation modalities (low frequency, iTBS5). rTMS is validated as an indication for the treatment of MDD by all learned societies and regulatory authorities in a large number of countries, except in France. Limiting factors concern the lack of knowledge of the action mechanisms, due in particular to the absence of studies based on animal models, the focused application of TMS in rodents being a challenge that few teams have mastered. The rationale for the therapeutic use in the treatment of MDD is now based on some functional brain imaging data showing that rTMS induces a lasting change in brain activity at the site of stimulation (CPFDL) but also in remote interconnected areas such as the limbic region or the amygdala. The DEPSTIM clinical project is part of a translational project with a fundamental approach in rodents.

The main objective is to demonstrate that remission following rTMS of CPFDL occurs via the activation of CPFDL projections to these dysfunctional subcortical areas in MDD.

With a prospective, open design, this study aims to evaluate the impact of iTBS over the left DLPFC on neuronal mechanisms of adults suffering from MDD. Subjects will be submitted to 25 intermittent TBS (iTBS) stimulation sessions for five consecutive days (5 sessions of 9.5 minutes/day, 1,800 pulses per session, 90% of resting motor threshold, placed over the left DLPFC, as mentionned by Cole et al, 2018 (Stanford Neuromodulation Therapy: SNT)). Baseline measures will be compared to those obtained immediately after the end of sessions (Day 5 (D5): short-term effects with HR-EEG analysis), and 30 days (D30) later (long-term effects with MRI analysis).

Being tested
iTBS
Keywords
depression, iTBS, neuronal mechanism, MRI, EEG
Medical subject headings
Depressive Disorder, Major, Depression

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • iTBSDevice

    25 active iTBS sessions (5 sessions of 9.5 minutes/day, 1,800 pulses per session, 90% of resting motor threshold, placed over the left DLPFC)

Study groups in NCT05121129
Study groupRoleWhat they receive
iTBSExperimentalSubjects suffering of MDD assigned to start the trial by 25 sessions of iTBS applied in left DLPFC
Receives: Device: iTBS

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change from baseline connectivity with theta wave on EEG at D5 (immediate effect) :

    changes in brain connectivity will be analyzed with theta wave

    Measured: baseline (Day 0), Day 5 post-treatment

  2. Change from baseline connectivity with beta wave in EEG at D5 (immediate effect)

    changes in brain connectivity will be analyzed with beta wave

    Measured: baseline (Day 0), Day 5 post-treatment

  3. Change from baseline connectivity with P3 wave EEG at D5 (immediate effect)

    changes in brain connectivity will be analyzed with P3 wave

    Measured: baseline (Day 0), Day 5 post-treatment

  4. Change from baseline connectivity with fMRI at D30 (prolonged effect) : Resting State Magnetic Resonance Imaging (MRI)

    Resting State MRI will allow us to investigate the functional connectivity in the brain, by looking at resting state networks

    Measured: baseline (Day 0), Day 30 post-treatment

Secondary outcomes (13)
  1. Severity of depressive symptoms evaluated by the clinician

    Score achieved on the validated clinician questionnaire Quick Inventory of Depressive Symptomatology (QIDS-C16) evaluating the severity of depressive symptoms.

    The QIDS-C16 was derived from specified items in the IDS-C30, clinician-rated scale to assess the severity of a participant's depressive symptoms. Total scores range from 0-27, with a score of 0 indicating no depression and a score of 27 indicating the most severe depression. Negative change from baseline values indicate improvement in the severity of depression.

    Measured: baseline (Day 0), Day 5 (end of iTBS sessions), Day 12 and Day 30 post-iTBS

  2. Severity of depressive symptoms evaluated by the patient

    Score achieved on the validated self-reported (QIDS-SR16) evaluating the severity of depressive symptoms. QIDS-SR-16 is a standard questionnaire "The Quick Inventory of Depressive Symptomatology" (16-Item) (Self-Report). This covers questions on falling asleep, sleep during the night, waking up , sleeping too much, feeling sad ,appetite, weight, concentration , how they view themselves, thoughts of death and suicide, general interests, energy levels, feeling slowed down , feeling restless.

    Measured: baseline (Day 0), Day 5 (end of iTBS sessions), Day 12 and Day 30 post-iTBS

  3. Impulsivity

    Score achieved on the validated Barratt Impulsiveness Scale (BIS-10) evaluating impulsivity. The French version of the BIS-10 is a self-rated 34 item questionnaire, composed by three subscales: motor-impulsivity, cognitive-impulsivity and non-planning-impulsivity. Each item is scored on a 0 to 4 points scale. Higher scores indicate higher levels of impulsivity.

    Measured: baseline (Day 0), Day 5 (end of iTBS sessions), Day 12 and Day 30 post-iTBS

  4. Average adjusted pump scores on the Balloon Analogue Risk Task (BART)

    In the BART participants blow up a series of virtual balloons. With each pump: (a) they earn 5 cents that accumulate in a temporary reserve, but (b) the likelihood of the balloon exploding increases. When this occurs participants lose the money in their temporary reserve. At any time, participants can choose to transfer their earnings to a permanent savings bank (and move to the next balloon). Thus, participants weigh the likelihood of the negative outcome (i.e., the balloon exploding and losing money) with the potential gains (i.e., 5 cents per pump). In the low ambiguity version of the task, the likelihood of the balloon exploding is known. In the high ambiguity version, the likelihood of the balloon exploding is unknown. The average adjusted pump score = average number of pumps on trials in which the balloons did not explode.

    Measured: baseline (Day 0), Day 12 post-iTBS

  5. Delay Discounting

    Score achieved on the validated MCQ scale (Monetary Choice Questionnaire), assessing delay discounting. Participants will be asked to make a series of hypothetical choices between small, sooner (impulsive) vs. larger, later (self controlled) hypothetical monetary outcomes

    Measured: baseline (Day 0), Day 5 (end of iTBS sessions), Day 12 and Day 30 post-iTBS

  6. Dimensions of personality

    Based on the Five-Factor Model, personality traits will be assessed by the French Big Five Inventory questionnaire (BFI-Fr). The BFI-Fr contains 45 self-descriptive statements that assess the 5 personality traits: neuroticism (which refers to a propensity to experience negative emotions, distress, and anxiety), extraversion (a propensity to be energetic, sociable, and experience positive emotions); openness to experience (the tendency to be curious, imaginative, and to entertain new ideas, values, and experiences); conscientiousness (reflecting self-disciplined, planful, and organized); and agreeableness (which refers to cooperativeness and altruism). Each item was rated on a 5-point Likert scale ranging from 1 (strongly disagree) to 5 (strongly agree). All items will be recoded in the direction of the trait label, and the mean will be taken across items for each personality trait.

    Measured: baseline (Day 0), Day 5 (end of iTBS sessions), Day 12 and Day 30 post-iTBS

  7. Motivation

    Score achieved on the validated EEfRT (Effort Expenditure for Rewards Task as an Objective Measure of Motivation and Anhedonia) experimental task. A measure of effort-based decision-making in humans, the Effort Expenditure for Reward Task (EEfRT), will be used. The EEfRT requires participants to choose between a low-effort, low reward task vs a high-effort, high reward task. Willingness to exert effort, or reward motivation, is measured by taking the average number of hard task choices from the first 50 trials.

    Measured: baseline (Day 0), Day 12 post-iTBS

  8. Social exclusion

    Score achieved on the validated CyberBall experimental task: a ball tossing playing game in which the experimentor can control the number of throws received by the participants. The task is into 2 parts : first, inclusion condition (Participating in wich they will receive 33% of the throw : 10 in a total of 30) and second, exclusion condition (Participating in wich they will receive 2 time the ball in the 10 first throw then none of them in the last 20 throw).

    Measured: baseline (Day 0), Day 12 post-iTBS

  9. Cognitive assessment

    neuropsychological assessments included in Rapid battery tests (Bereau et al., 2015)

    Measured: baseline (Day 0), Day 30 post-iTBS

  10. To assess the optimal b-value (a key parameter) for DTI (Diffusion Tensor Imaging)

    b-value is a key technique parameter for DTI, which will decide the quality of DTI image.

    DTI is a sensitive probe of cellular structure that works by measuring the diffusion of water molecules. The measured quantity is the diffusion coefficient, a proportionality constant that relates diffusive flux to a concentration gradient and has units of mm2/s.

    Measured: baseline (Day 0), Day 30 post-iTBS

  11. C-Reactive Protein (CRP) concentrations

    C-reactive protein rate

    Measured: baseline (Day 0), Day 12 post-iTBS

  12. Serum Interleukin-6 (IL-6) level

    the measurement of serum IL-6 level in blood

    Measured: baseline (Day 0), Day 12 post-iTBS

  13. Smoking (tobacco addiction) according to the Fagerström test

    Scores achieved on the validated Fagerström scale. The Fagerström test consists of six questions. A score of 0 - 10 is obtained depending on the answers given. A score of 0 - 2 = zero addiction, 3 - 4 = slight addiction, 5 - 6 = moderate addiction, 7 ou 8 heavy addiction and 9 - 10 = very heavy addiction.

    Measured: baseline (Day 0), Day 5 (end of iTBS sessions), Day 12 and Day 30 post-iTBS

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Nov 2021
  2. Study start13 Oct 2021
  3. Primary completion9 Mar 2023 (estimated)
  4. Study completion9 Apr 2023 (estimated)

Resources

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
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05121129
Sponsor's protocol ID
2020/477
Acronym
DEPSTIM
Status last verified
Dec 2022
First submitted
13 Oct 2021
Last updated
19 Dec 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A study testing iTBS in people with Depressive Disorder, Major, run by Centre Hospitalier Universitaire de Besancon 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 10 inclusion and 12 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: status not confirmed, as of the sponsor's last update on 19 Dec 2022. 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. 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?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Emmanuel HAFFEN, Professor (+33381218154, emmanuel.haffen@univ-fcomte.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change from baseline connectivity with theta wave on EEG at D5 (immediate effect) : (time frame: baseline (Day 0), Day 5 post-treatment). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 19 Dec 2022.

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