Major Depressive DisorderNCT04032015
rTMS Study in Depression to Evaluate the Relationship Between Brain Plasticity and Clinical Outcome
A study testing TMS in people with Major Depressive Disorder, run by Stanford University.
Trial summary
Depression is a highly prevalent condition characterized by persistent low mood, energy, and activity that can affect one's thoughts, mood, behavior, and sense of well-being. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulatory technique, is an effective treatment for depression. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- TMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2020to 1 Jun 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- English-speaking
- Right-handed
- Ages 18-65
- Depression diagnosis as assessed through an in-depth interview
- Failed at least 1 antidepressant medication
- Without current/history of neurological disorders or seizures or risk of seizures
Who cannot join
- A contraindication for MRIs (e.g. implanted metal)
- History of head trauma with loss of consciousness
- History of seizures
- Neurological or uncontrolled medical disease
- Active substance abuse
- Diagnosis of psychotic or bipolar disorder
Show all 9Show fewer
- Prior history of ECT or rTMS failure
- Currently taking medications that substantially reduce seizure threshold
- Currently pregnant or breastfeeding.
About this study
Official title: Randomized, Sham-controlled rTMS Trial in Depression to Evaluate the Relationship of Brain Plasticity and Clinical Outcome
Depression is a highly prevalent condition characterized by persistent low mood, energy, and activity that can affect one's thoughts, mood, behavior, and sense of well-being. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulatory technique, is an effective treatment for depression. However, remission rates are suboptimal and ideal stimulation parameters are unknown. The overarching goal of this study is to elucidate how brain changes accumulate during rTMS, and how these changes relate to clinical outcome. I plan to recruit patients with medication-resistant depression and treat with four weeks of rTMS in a randomized, double-blind, sham-controlled fashion. I will measure brain changes using TMS-EEG and determine how these changes relate to clinical outcome. This study will 1) test how brain changes relate to clinical outcome and 2) establish a computational model to help predict outcome and propose novel treatment protocols.
Read the detailed description
Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depressive disorder, but remission rates are 20-40%, and ideal stimulation parameters are unknown. rTMS is thought to work by changing the synaptic strength of neurons. The ability of our brain to make these changes is referred to as plasticity. rTMS-induced changes are thought to build with successive treatment sessions, a process referred to as metaplasticity. While both plasticity and metaplasticity are well-established in single cell physiology, relevance to rTMS in humans remains unknown. To improve clinical efficacy, the investigators seek to understand 1) the neural response to a single rTMS session (plasticity), 2) the neural response to repeated daily rTMS sessions (metaplasticity), and 3) whether computational models of plasticity based on single-cell physiology apply to human patients receiving rTMS for depression.
Goals of the study are as follows:
- establish a detailed mechanistic understanding of the brain changes during current rTMS treatment
- identify clinically meaningful electrophysiological biomarkers for rTMS treatment
- establish a computational model to help predict both brain and clinical changes.
This project tests the hypothesis that neural changes that accumulate during rTMS treatment can predict clinical outcome. Participants will first complete a screening procedure to determine eligibility based on the inclusion/exclusion criteria. If the participants are not eligible, no further study procedures will be conducted. Eligible participants will be randomized to four weeks (20 sessions) of daily 10Hz left dorsolateral prefrontal cortex (DLPFC) active or sham rTMS. Following the completion of sham treatment, participants will be offered open-label active rTMS treatment for four weeks to ensure that all participants receive active treatment if desired. Single pulse TMS-evoked potential (TEP), a well-studied causal EEG measure of brain excitability, will be measured before, during, and after every rTMS session. TEPs will be measured locally in the left lateral prefrontal cortex and compared to downstream sites in parietal and medial prefrontal cortex.
Aim 1: To determine the electrophysiological response to single and repeated rTMS sessions in depression. Through this aim, I will establish a detailed mechanistic understanding of the electrophysiological effects of rTMS treatments.
Aim 2: To determine the relationship between brain state, plasticity, metaplasticity, and antidepressant response in depression. Through this aim, I will identify clinically meaningful electrophysiological biomarkers for rTMS treatment.
Aim 3: To test whether a computational model of metaplasticity applies to human patients. This computational model will help predict both neurophysiological and clinical changes.
Findings from this study will provide the basis for novel stimulation protocols that will maximize clinically-relevant brain changes and improve clinical outcomes.
- Conditions
- Major Depressive Disorder
- Being tested
- TMS
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TMSDevice
Device used to administer electromagnetic fields to the brain to alter connectivity patterns
| Study group | Role | What they receive |
|---|---|---|
| rTMS treatment | Active comparator | rTMS will be delivered for 20 sessions over 4 weeks. Active 10 Hz rTMS will be delivered using neuro-navigation based on participants' own MRI images. Daily treatment regiments will last 30 minutes and rTMS will be delivered at 120% of the participant's motor threshold. Participants will be monitored during the rTMS sessions for adverse events and/or side effects. Receives: Device: TMS |
| Sham treatment | Sham comparator | Sham rTMS will be delivered for 20 sessions over 4 weeks. To maximize sham validity, both 1) a direction-sensor TMS coil will alert the operators to flip the coil if the wrong side is being used, and 2) low-intensity 10Hz electrical stimulation will be applied to scalp electrodes under the coil for sham and placed but not activated in the active arm. The rTMS coil will be positioned using neuro-navigation based on participants' own MRI images, mimicking active rTMS treatment. Daily treatment regiments will last 30 minutes and sham rTMS will be delivered at 120% of the participant's motor threshold. Participants will be monitored during the sham rTMS sessions for adverse events and/or side effects.
Upon completing the 20 sham sessions, participants are unblinded and offered 20 treatments of active rTMS. The open-label treatment would follow the active rTMS treatment protocol. Receives: Device: TMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
TMS-EEG change
Change in TMS-EEG measures will be assessed before, during, and after each treatment session. These changes will be compared to clinical outcome to identify clinically-relevant biomarkers.
Measured: Up to 1 month
Hamilton Depression Rating Scale (HamD)
Clinician administered scale to assess depression is a 24-item clinician-administered assessment utilized as a way of determining a patient's level of depression before, during, and after treatment. It takes approximately 15-20 minutes to complete the interview and score the results.
Measured: Up to 6 months after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2019
- Study start1 Jan 2020 (estimated)
- Primary completion1 Jun 2023 (estimated)
- Study completion1 Jun 2023 (estimated)
Why it stopped: Funding not currently active
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Corey Keller, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04032015
- Sponsor's protocol ID
- 133611
- Status last verified
- Apr 2021
- First submitted
- 22 Jul 2019
- Last updated
- 14 Apr 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Sham-controlled rTMS Trial in Depression to Evaluate the Relationship of Brain Plasticity and Clinical Outcome
- ClinicalTrials.gov ID
- NCT04032015
- Acronym / sponsor ID
- 133611
- Conditions
- Major Depressive Disorder
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Funding not currently active
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- 1 Jan 2020 (estimated)
- Primary completion
- 1 Jun 2023 (estimated)
- Study completion
- 1 Jun 2023 (estimated)
- First posted
- 25 Jul 2019 (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.
Depression is a highly prevalent condition characterized by persistent low mood, energy, and activity that can affect one's thoughts, mood, behavior, and sense of well-being. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulatory technique, is an effective treatment for depression. However, remission rates are suboptimal and ideal stimulation parameters are unknown. The overarching goal of this study is to elucidate how brain changes accumulate during rTMS, and how these changes relate to clinical outcome. I plan to recruit patients with medication-resistant depression and treat with four weeks of rTMS in a randomized, double-blind, sham-controlled fashion. I will measure brain changes using TMS-EEG and determine how these changes relate to clinical outcome. This study will 1) test how brain changes relate to clinical outcome and 2) establish a computational model to help predict outcome and propose novel treatment protocols.
Detailed description
Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depressive disorder, but remission rates are 20-40%, and ideal stimulation parameters are unknown. rTMS is thought to work by changing the synaptic strength of neurons. The ability of our brain to make these changes is referred to as plasticity. rTMS-induced changes are thought to build with successive treatment sessions, a process referred to as metaplasticity. While both plasticity and metaplasticity are well-established in single cell physiology, relevance to rTMS in humans remains unknown. To improve clinical efficacy, the investigators seek to understand 1) the neural response to a single rTMS session (plasticity), 2) the neural response to repeated daily rTMS sessions (metaplasticity), and 3) whether computational models of plasticity based on single-cell physiology apply to human patients receiving rTMS for depression.
Goals of the study are as follows:
- establish a detailed mechanistic understanding of the brain changes during current rTMS treatment
- identify clinically meaningful electrophysiological biomarkers for rTMS treatment
- establish a computational model to help predict both brain and clinical changes.
This project tests the hypothesis that neural changes that accumulate during rTMS treatment can predict clinical outcome. Participants will first complete a screening procedure to determine eligibility based on the inclusion/exclusion criteria. If the participants are not eligible, no further study procedures will be conducted. Eligible participants will be randomized to four weeks (20 sessions) of daily 10Hz left dorsolateral prefrontal cortex (DLPFC) active or sham rTMS. Following the completion of sham treatment, participants will be offered open-label active rTMS treatment for four weeks to ensure that all participants receive active treatment if desired. Single pulse TMS-evoked potential (TEP), a well-studied causal EEG measure of brain excitability, will be measured before, during, and after every rTMS session. TEPs will be measured locally in the left lateral prefrontal cortex and compared to downstream sites in parietal and medial prefrontal cortex.
Aim 1: To determine the electrophysiological response to single and repeated rTMS sessions in depression. Through this aim, I will establish a detailed mechanistic understanding of the electrophysiological effects of rTMS treatments.
Aim 2: To determine the relationship between brain state, plasticity, metaplasticity, and antidepressant response in depression. Through this aim, I will identify clinically meaningful electrophysiological biomarkers for rTMS treatment.
Aim 3: To test whether a computational model of metaplasticity applies to human patients. This computational model will help predict both neurophysiological and clinical changes.
Findings from this study will provide the basis for novel stimulation protocols that will maximize clinically-relevant brain changes and improve clinical outcomes.
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 |
|---|---|---|
| rTMS treatment | Active comparator | Device: TMSrTMS will be delivered for 20 sessions over 4 weeks. Active 10 Hz rTMS will be delivered using neuro-navigation based on participants' own MRI images. Daily treatment regiments will last 30 minutes and rTMS will be delivered at 120% of the participant's motor threshold. Participants will be monitored during the rTMS sessions for adverse events and/or side effects. |
| Sham treatment | Sham comparator | Device: TMSSham rTMS will be delivered for 20 sessions over 4 weeks. To maximize sham validity, both 1) a direction-sensor TMS coil will alert the operators to flip the coil if the wrong side is being used, and 2) low-intensity 10Hz electrical stimulation will be applied to scalp electrodes under the coil for sham and placed but not activated in the active arm. The rTMS coil will be positioned using neuro-navigation based on participants' own MRI images, mimicking active rTMS treatment. Daily treatment regiments will last 30 minutes and sham rTMS will be delivered at 120% of the participant's motor threshold. Participants will be monitored during the sham rTMS sessions for adverse events and/or side effects. Upon completing the 20 sham sessions, participants are unblinded and offered 20 treatments of active rTMS. The open-label treatment would follow the active rTMS treatment protocol. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- English-speaking
- Right-handed
- Ages 18-65
- Depression diagnosis as assessed through an in-depth interview
- Failed at least 1 antidepressant medication
Key exclusion criteria (9 listed)
- A contraindication for MRIs (e.g. implanted metal)
- History of head trauma with loss of consciousness
- History of seizures
- Neurological or uncontrolled medical disease
- Active substance abuse
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 |
|---|---|---|
| TMSDevice used to administer electromagnetic fields to the brain to alter connectivity patterns | Device | Sham treatment, rTMS treatment |
Primary outcome
TMS-EEG change
Time frame: Up to 1 month
Change in TMS-EEG measures will be assessed before, during, and after each treatment session. These changes will be compared to clinical outcome to identify clinically-relevant biomarkers.
Hamilton Depression Rating Scale (HamD)
Time frame: Up to 6 months after treatment
Clinician administered scale to assess depression is a 24-item clinician-administered assessment utilized as a way of determining a patient's level of depression before, during, and after treatment. It takes approximately 15-20 minutes to complete the interview and score the results.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2021.
- Individual participant dataSharing planned: Undecided
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A study testing TMS in people with Major Depressive Disorder, run by Stanford University.
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 9 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: withdrawn, as of the sponsor's last update on 14 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
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 was withdrawn before enrolling participants, so there are no results.
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?
TMS-EEG change (time frame: Up to 1 month). The study lists 2 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 14 Apr 2021; AzTrials last refreshed its copy on 28 Oct 2026.