Major Depressive DisorderNARSADNCT04014959
Mini Theta Burst TMS in MDD Patients
A study testing Transcranial Magnetic Stimulation in people with Major Depressive Disorder, run by University of Pennsylvania at 1 site in United States.
Trial summary
This is not a treatment study. In this study, the researchers are primarily interested in examining whether functional MRI (fMRI)-guided transcranial magnetic stimulation (TMS) may be more effective than traditional TMS methods at temporarily influencing neural circuit communication. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Transcranial Magnetic Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Jul 2017to 30 Jun 2021
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 18 to 60 years old, inclusive
- Right-handed
- Currently experiencing a major depressive episode (MDD)
- Capacity to give informed consent and follow study procedures
- Command of English language to understand/ respond to written and verbal instructions
Who cannot join
- MRI contraindications (i.e., metal in body, claustrophobia, etc.)
- TMS contraindications (i.e., seizure disorder)
- Diagnosis of exclusionary psychiatric disorder (i.e., schizophrenia, bipolar)
- Current use of psychiatric medication and unable/ willing to safely withdraw
- Refusal to abstain from alcohol or drugs for duration of study
- Medication use that reduces seizure threshold
Show all 9Show fewer
- Medication that interferes with blood flow (i.e., opioids, antihypertensive)
- Known neurological disorder or significant disability that interferes with study procedures
- Woman who is pregnant or breastfeeding
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: Mini Theta Burst TMS to Promote Brain Plasticity Indexed by fMRI in MDD Patients
This is not a treatment study.
In this study, the researchers are primarily interested in examining whether functional MRI (fMRI)-guided transcranial magnetic stimulation (TMS) may be more effective than traditional TMS methods at temporarily influencing neural circuit communication. The investigators test this by combining TMS and fMRI technologies to probe and modulate brain activity.
If the novel fMRI-guided TMS stimulation used in this study is more effective than traditional methods, future studies may utilize similar personalized TMS targeting methods to yield even better clinical outcomes.
Read the detailed description
This study will involve a baseline Magnetic Resonance Imaging (MRI) scan, Transcranial Magnetic Stimulation (TMS), and TMS interleaved with functional MRI (fMRI) scans.
After screening, eligible participants will undergo a 1-hour MRI scan, encompassing structural and functional scans to establish TMS stimulation targets for subsequent visits. During the baseline TMS/fMRI session or pre-intervention TMS/fMRI, single pulses of TMS and a short round of repetitive TMS (rTMS) will be administered to the participant's individualized target while functional MRI scans (fMRI) are collected. Following this, participants will commence a short TMS intervention regimen involving daily rTMS over 3 consecutive days. The day after the intervention, participants will undergo another TMS/fMRI session, or the post-intervention TMS/fMRI, to capture potential changes from the 3-day intervention.
Clinical assessments will be conducted at baseline before the first TMS/fMRI session and again after the final TMS/fMRI session to assess symptom changes.
- Conditions
- Major Depressive Disorder
- Being tested
- Transcranial Magnetic Stimulation
- Keywords
- depression, TMS, fMRI
- 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.
Transcranial Magnetic StimulationDevice
Transcranial Magnetic Stimulation (TMS) is a non-invasive form of brain stimulation. TMS can influence activity in various brain regions, and it allows researchers to test or modify brain circuit communication. Repetitive TMS (rTMS) is FDA-approved for depression treatment.
TMS is administered over 5 study visits: an initial TMS/fMRI session, a 3-day TMS intervention regimen, and a post-intervention TMS/fMRI session. During TMS/fMRI sessions, participants receive single pulses of TMS pre/post a short round of Intermittent Theta Burst Stimulation (iTBS), a modified rTMS protocol. Throughout the 3-day intervention regimen, participants receive two full rounds of iTBS daily.
All study participants receive active TMS.
| Study group | Role | What they receive |
|---|---|---|
| All Participants | Experimental | All participants follow the same procedures. Receives: Device: Transcranial Magnetic Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Evoked Functional Brain Activity Pre/Post Short iTBS Stimulation Before and After the 3-Day TMS Intervention Regimen
Change in subgenual anterior cingulate evoked response (fMRI BOLD) at all four timepoints across the two TMS/fMRI scan sessions: pre-intervention and preceding a single round of iTBS in the scanner (pre-tx, pre-iTBS); pre-intervention, following single iTBS in the scanner (pre-tx, post-iTBS); post intervention, preceding iTBS in the scanner (post-tx, pre-iTBS); and post-intervention, post-iTBS in the scanner (post-tx, post-iTBS).
Greater negative change is associated with more clinical improvement.
Measured: 5 days
Secondary outcomes (1)
Change in Depression, Anxiety and Stress Scale (DASS-21) Score Pre/Post the 3-Day TMS Intervention Regimen
The Depression, Anxiety, and Stress Scale (DASS-21) is a self-report tool with 21 items, assessing depression, anxiety, and stress levels. The scale scores range from 0 to 63, with higher scores indicating more severe or frequent emotional symptoms. The change in DASS-21 score will be evaluated pre and post the 3-day TMS Intervention Regimen.
Measured: Up to one week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2019
- Study start14 Jul 2017
- Primary completion30 Jun 2020
- Study completion30 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe 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
- Not applicable
- Intervention model
- Single group
- Model description
- All subjects receive active TMS to their individualized fMRI-guided target. Participants will first receive TMS in the MRI scanner, then over the course of 3-Day TMS Intervention Regimen, and lastly in a final MRI scan.
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Desmond Oathes, University of Pennsylvania
- Investigators
- Desmond Oathes, PhD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04014959
- Sponsor's protocol ID
- 825761
- Acronym
- NARSAD
- Status last verified
- Mar 2024
- First submitted
- 1 Jul 2019
- Last updated
- 2 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Publications
Oathes DJ, Duprat RJ, Reber J, Liang X, Scully M, Long H, Deluisi JA, Sheline YI, Linn KA. Non-Invasively Targeting, Probing, and Modulating a Deep Brain Circuit for Depression Alleviation. Nat Ment Health. 2023 Dec;1(12):1033-1042. doi: 10.1038/s44220-023-00165-2. Epub 2023 Nov 27.
PubMed 41726164Bossus L, Dickson J, Blaine C, Khalilkhani H, Khan A, Oathes DJ. Causal connectivity maps derived from single-pulse interleaved TMS/fMRI. Sci Rep. 2026 Jan 22;16(1):3070. doi: 10.1038/s41598-025-23684-7.
PubMed 41571696
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mini Theta Burst TMS to Promote Brain Plasticity Indexed by fMRI in MDD Patients
- ClinicalTrials.gov ID
- NCT04014959
- Acronym / sponsor ID
- NARSAD / 825761
- Conditions
- Major Depressive Disorder
- Keywords
- depression, TMS, fMRI
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 14 Jul 2017 (actual)
- Primary completion
- 30 Jun 2020 (actual)
- Study completion
- 30 Jun 2021 (actual)
- First posted
- 10 Jul 2019 (actual)
- Results
- Posted 2 Apr 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is not a treatment study.
In this study, the researchers are primarily interested in examining whether functional MRI (fMRI)-guided transcranial magnetic stimulation (TMS) may be more effective than traditional TMS methods at temporarily influencing neural circuit communication. The investigators test this by combining TMS and fMRI technologies to probe and modulate brain activity.
If the novel fMRI-guided TMS stimulation used in this study is more effective than traditional methods, future studies may utilize similar personalized TMS targeting methods to yield even better clinical outcomes.
Detailed description
This study will involve a baseline Magnetic Resonance Imaging (MRI) scan, Transcranial Magnetic Stimulation (TMS), and TMS interleaved with functional MRI (fMRI) scans.
After screening, eligible participants will undergo a 1-hour MRI scan, encompassing structural and functional scans to establish TMS stimulation targets for subsequent visits. During the baseline TMS/fMRI session or pre-intervention TMS/fMRI, single pulses of TMS and a short round of repetitive TMS (rTMS) will be administered to the participant's individualized target while functional MRI scans (fMRI) are collected. Following this, participants will commence a short TMS intervention regimen involving daily rTMS over 3 consecutive days. The day after the intervention, participants will undergo another TMS/fMRI session, or the post-intervention TMS/fMRI, to capture potential changes from the 3-day intervention.
Clinical assessments will be conducted at baseline before the first TMS/fMRI session and again after the final TMS/fMRI session to assess symptom changes.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- All subjects receive active TMS to their individualized fMRI-guided target. Participants will first receive TMS in the MRI scanner, then over the course of 3-Day TMS Intervention Regimen, and lastly in a final MRI scan.
| Arm | Type | Receives |
|---|---|---|
| All Participants | Experimental | Device: Transcranial Magnetic StimulationAll participants follow the same procedures. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 18 to 60 years old, inclusive
- Right-handed
- Currently experiencing a major depressive episode (MDD)
- Capacity to give informed consent and follow study procedures
- Command of English language to understand/ respond to written and verbal instructions
Key exclusion criteria (9 listed)
- MRI contraindications (i.e., metal in body, claustrophobia, etc.)
- TMS contraindications (i.e., seizure disorder)
- Diagnosis of exclusionary psychiatric disorder (i.e., schizophrenia, bipolar)
- Current use of psychiatric medication and unable/ willing to safely withdraw
- Refusal to abstain from alcohol or drugs for duration of study
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 |
|---|---|---|
| Transcranial Magnetic StimulationTranscranial Magnetic Stimulation (TMS) is a non-invasive form of brain stimulation. TMS can influence activity in various brain regions, and it allows researchers to test or modify brain circuit communication. Repetitive TMS (rTMS) is FDA-approved for depression treatment. TMS is administered over 5 study visits: an initial TMS/fMRI session, a 3-day TMS intervention regimen, and a post-intervention TMS/fMRI session. During TMS/fMRI sessions, participants receive single pulses of TMS pre/post a short round of Intermittent Theta Burst Stimulation (iTBS), a modified rTMS protocol. Throughout the 3-day intervention regimen, participants receive two full rounds of iTBS daily. All study participants receive active TMS. | Device | All Participants |
Primary outcome
Changes in Evoked Functional Brain Activity Pre/Post Short iTBS Stimulation Before and After the 3-Day TMS Intervention Regimen
Time frame: 5 days
Change in subgenual anterior cingulate evoked response (fMRI BOLD) at all four timepoints across the two TMS/fMRI scan sessions: pre-intervention and preceding a single round of iTBS in the scanner (pre-tx, pre-iTBS); pre-intervention, following single iTBS in the scanner (pre-tx, post-iTBS); post intervention, preceding iTBS in the scanner (post-tx, pre-iTBS); and post-intervention, post-iTBS in the scanner (post-tx, post-iTBS). Greater negative change is associated with more clinical improvement.
1 secondary outcome
Change in Depression, Anxiety and Stress Scale (DASS-21) Score Pre/Post the 3-Day TMS Intervention Regimen
Time frame: Up to one week
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41726164Oathes DJ, Duprat RJ, Reber J, Liang X, Scully M, Long H, Deluisi JA, Sheline YI, Linn KA. Non-Invasively Targeting, Probing, and Modulating a Deep Brain Circuit for Depression Alleviation. Nat Ment Health. 2023 Dec;1(12):1033-1042. doi: 10.1038/s44220-023-00165-2. Epub 2023 Nov 27.
- Derived from this study: PubMed 41571696Bossus L, Dickson J, Blaine C, Khalilkhani H, Khan A, Oathes DJ. Causal connectivity maps derived from single-pulse interleaved TMS/fMRI. Sci Rep. 2026 Jan 22;16(1):3070. doi: 10.1038/s41598-025-23684-7.
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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.
Desmond Oathes, PhD principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcranial Magnetic Stimulation in people with Major Depressive Disorder, run by University of Pennsylvania at 1 site in United States.
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 5 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: finished, as of the sponsor's last update on 2 Apr 2024. 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 United States. 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?
Yes. Results are posted in the registry (first posted 2 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Changes in Evoked Functional Brain Activity Pre/Post Short iTBS Stimulation Before and After the 3-Day TMS Intervention Regimen (time frame: 5 days). 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 NCT04014959, which also lists 2 linked publications.
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 2 Apr 2024.