Treatment Resistant DepressionNCT06052137
Open Label - Personalized Therapeutic Neuromodulation for Anhedonic Depression
A study testing Active TBS-DLPFC and TBS-DMPFC in people with Treatment Resistant Depression, run by Stanford University at 1 site in United States.
Trial summary
This study will investigate the anti-anhedonic efficacy of a novel neurostimulation strategy termed accelerated intermittent theta burst stimulation (aiTBS) in participants with treatment resistant depression (TRD). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Treatment Resistant Depression
- What is being tested?
- Active TBS-DLPFC and TBS-DMPFC
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Dec 2023to Oct 2025
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or Female, between the ages of 18 and 80 at the time of screening.
- Able to read, understand, and provide written, dated informed consent prior to screening. Proficiency in English sufficient to complete questionnaires / follow instructions during fMRI assessments and aiTBS interventions. Stated willingness to comply with all study procedures, including availability for the duration of the study, and to communicate with study personnel about adverse events and other clinically important information.
- Currently diagnosed with Major Depressive Disorder (MDD) and meets criteria for a Major Depressive Episode, according to the criteria defined in the Diagnosis and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5).
- MADRS score of ≥20 at screening (Visit 1).
- TMS naive for one of the following areas: DLPCF or DMPFC
- The dose of the primary antidepressant medication (if applicable) must be stable for 6 weeks prior to baseline, and participant must agree to continue at this dose throughout the study period.
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- In good general health, as evidenced by medical history.
- For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation.
- Agreement to adhere to Lifestyle Considerations throughout study duration.
- Lifestyle Considerations:
- Abstain from becoming pregnant from the screening visit (Visit 1) until after the final study visit (Visit 10).
- Abstain from caffeine- or xanthine-containing products (e.g., coffee, tea, cola drinks, and chocolate) for 3 hours before the start of each dosing session until after the final TMS session.
- Abstain from alcohol for 24 hours before the start of each dosing session until after collection of the final MRI.
- Participants who use tobacco products will be instructed that use of cigarettes will not be allowed during the study.
Who cannot join
- Pregnancy
- History of or current psychotic disorder or bipolar disorder
- Severe borderline personality disorder.
- Diagnosis of Intellectual Disability or Autism Spectrum Disorder
- Primary psychiatric condition other than MDD requiring treatment except stable comorbid anxiety disorder
- Current moderate or severe substance use disorder or demonstrating signs of acute substance withdrawal
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- Urine screening test positive for illicit substances
- Acute suicide risk based on clinical judgement or a suicide attempt (as defined by the C-SSRS) within the past one year
- Any history of ECT (greater than 8 sessions) without meeting responder criteria
- Recent (within 4 weeks of any clinical effect) or concurrent use of rapid acting antidepressant agent (i.e., ketamine or a course of ECT)
- History of significant neurologic disease, including dementia, Parkinson's or Huntington's disease, brain tumor, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma
- Untreated or insufficiently treated endocrine disorder.
- Contraindication to receiving rTMS (e.g., metal in head, history of seizure, known brain lesion)
- Contraindication to MRI (ferromagnetic metal in their body)
- Treatment with an investigational drug or other intervention within the study period
- Depth-adjusted aiTBS treatment dose > 65% maximum stimulator output (MSO)
- Unstable symptoms between screening and baseline as defined by a ≥ 30% change in MADRS score.
- Any other condition deemed by the PD to interfere with the study or increase risk to the participant
Trial locations and contacts
1 site in 1 country.
About this study
This study will investigate the anti-anhedonic efficacy of a novel neurostimulation strategy termed accelerated intermittent theta burst stimulation (aiTBS) in participants with treatment resistant depression (TRD).
Read the detailed description
Repetitive transcranial magnetic stimulation (rTMS) is an established therapy for treatment-resistant depression. The approved method for treatment is 10Hz stimulation for 40 min over the left dorsolateral prefrontal cortex (L-DLPFC). This methodology has been effective in real world situations. The limitations of this approach include the duration of the treatment (approximately 40 minutes per treatment session, 5 days per week, for 4-8 weeks). Recently, the investigators have pursued modifying the treatment parameters to reduce treatment times with an accelerated treatment paradigm. This study aims to further study the accelerated protocol and examine changes in neuroimaging biomarkers.
- Conditions
- Treatment Resistant Depression
- Being tested
- Active TBS-DLPFC, TBS-DMPFC
- Keywords
- transcranial magnetic stimulation, theta burst
- Medical subject headings
- Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active TBS-DLPFCDevice
Participants will receive intermittent TBS to left DLPFC. The L-DLPFC will be targeted utilizing the Localite neuronavigation system. Stimulation intensity will be standardized at 90% of RMT and adjusted to the skull to cortical surface distance (see Nahas 2004).
Stimulation will be delivered to the L-DLPFC using a MagPro TMS system (MagVenture, Denmark).
TBS-DMPFCDevice
Participants will receive intermittent TBS to DMPFC. The DMPFC will be targeted utilizing the Localite neuronavigation system. Stimulation intensity will be standardized at 90% of RMT and adjusted to the skull to cortical surface distance (see Nahas 2004).
Stimulation will be delivered to the DMPFC using a MagPro TMS system (MagVenture, Denmark).
| Study group | Role | What they receive |
|---|---|---|
| Active TBS-DLPFC | Active comparator | The active group will receive theta-burst TMS DLPFC stimulation. Receives: Device: Active TBS-DLPFC |
| Active TBS-DMPFC | Active comparator | The active group will receive theta-burst TMS DMPFC stimulation. Receives: Device: TBS-DMPFC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in clinician-administered MADRS from Baseline to Week 1 post-treatment-initiation
The Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item clinician-administered scale, designed to be particularly sensitive to antidepressant treatment effects in patients with major depression. Score range of 0-60. A higher score is indicative of more depression.
Measured: Baseline, 1-week post-treatment-initiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2023
- Study start19 Dec 2023
- Primary completionOct 2025 (estimated)
- Study completionOct 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Treatment Resistant DepressionStudies 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
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David Spiegel, Stanford University
- Investigators
- David Spiegel, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06052137
- Sponsor's protocol ID
- 71771
- Status last verified
- Apr 2025
- First submitted
- 18 Sep 2023
- Last updated
- 4 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Label - Personalized Therapeutic Neuromodulation for Anhedonic Depression
- ClinicalTrials.gov ID
- NCT06052137
- Acronym / sponsor ID
- 71771
- Conditions
- Treatment Resistant Depression
- Keywords
- transcranial magnetic stimulation, theta burst
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- 19 Dec 2023 (actual)
- Primary completion
- Oct 2025 (estimated)
- Study completion
- Oct 2025 (estimated)
- First posted
- 25 Sep 2023 (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.
This study will investigate the anti-anhedonic efficacy of a novel neurostimulation strategy termed accelerated intermittent theta burst stimulation (aiTBS) in participants with treatment resistant depression (TRD).
Detailed description
Repetitive transcranial magnetic stimulation (rTMS) is an established therapy for treatment-resistant depression. The approved method for treatment is 10Hz stimulation for 40 min over the left dorsolateral prefrontal cortex (L-DLPFC). This methodology has been effective in real world situations. The limitations of this approach include the duration of the treatment (approximately 40 minutes per treatment session, 5 days per week, for 4-8 weeks). Recently, the investigators have pursued modifying the treatment parameters to reduce treatment times with an accelerated treatment paradigm. This study aims to further study the accelerated protocol and examine changes in neuroimaging biomarkers.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active TBS-DLPFC | Active comparator | Device: Active TBS-DLPFCThe active group will receive theta-burst TMS DLPFC stimulation. |
| Active TBS-DMPFC | Active comparator | Device: TBS-DMPFCThe active group will receive theta-burst TMS DMPFC stimulation. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Male or Female, between the ages of 18 and 80 at the time of screening.
- Able to read, understand, and provide written, dated informed consent prior to screening. Proficiency in English sufficient to complete questionnaires / follow instructions during fMRI assessments and aiTBS interventions. Stated willingness to comply with all study procedures, including availability for the duration of the study, and to communicate with study personnel about adverse events and other clinically important information.
- Currently diagnosed with Major Depressive Disorder (MDD) and meets criteria for a Major Depressive Episode, according to the criteria defined in the Diagnosis and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5).
- MADRS score of ≥20 at screening (Visit 1).
- TMS naive for one of the following areas: DLPCF or DMPFC
Key exclusion criteria (18 listed)
- Pregnancy
- History of or current psychotic disorder or bipolar disorder
- Severe borderline personality disorder.
- Diagnosis of Intellectual Disability or Autism Spectrum Disorder
- Primary psychiatric condition other than MDD requiring treatment except stable comorbid anxiety disorder
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 |
|---|---|---|
| Active TBS-DLPFCParticipants will receive intermittent TBS to left DLPFC. The L-DLPFC will be targeted utilizing the Localite neuronavigation system. Stimulation intensity will be standardized at 90% of RMT and adjusted to the skull to cortical surface distance (see Nahas 2004). Stimulation will be delivered to the L-DLPFC using a MagPro TMS system (MagVenture, Denmark). | Device | Active TBS-DLPFC |
| TBS-DMPFCParticipants will receive intermittent TBS to DMPFC. The DMPFC will be targeted utilizing the Localite neuronavigation system. Stimulation intensity will be standardized at 90% of RMT and adjusted to the skull to cortical surface distance (see Nahas 2004). Stimulation will be delivered to the DMPFC using a MagPro TMS system (MagVenture, Denmark). | Device | Active TBS-DMPFC |
Primary outcome
Change in clinician-administered MADRS from Baseline to Week 1 post-treatment-initiation
Time frame: Baseline, 1-week post-treatment-initiation
The Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item clinician-administered scale, designed to be particularly sensitive to antidepressant treatment effects in patients with major depression. Score range of 0-60. A higher score is indicative of more depression.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2025.
- Individual participant dataSharing planned: No
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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.
David Spiegel, MD principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active TBS-DLPFC and TBS-DMPFC in people with Treatment Resistant Depression, run by Stanford University 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 14 inclusion and 18 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: under way, not looking for participants, as of the sponsor's last update on 4 Apr 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 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?
This study is still under way. Results are not available in the source record yet.
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 clinician-administered MADRS from Baseline to Week 1 post-treatment-initiation (time frame: Baseline, 1-week post-treatment-initiation). 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 4 Apr 2025.