Treatment Resistant DepressionciTBSNCT04684706
Compressed Intermittent Theta Burst Stimulation
A study testing intermittent Theta Burst Stimulation in people with Treatment Resistant Depression, run by University of Pennsylvania at 2 sites in United States.
Trial summary
In this proposal the investigators will use an accelerated TMS protocol that concentrates the magnetic stimulation that would usually occur over 6 weeks into 10 treatment sessions per days, for 5 consecutive days in patient with treatment-refractory depression. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Treatment Resistant Depression
- What is being tested?
- intermittent Theta Burst Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 2 sitesUnited States
- Study dates
- 20 Feb 2020to 20 Jan 2027
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Gender, inclusive
- 18 - 70 years of age
- Meets Diagnostic and Statistical Manual of Mental Disorders criteria for primary diagnosis of MDD
- Patients must be fluent in English
- Participants must have the ability to provide consent
- Montgomery Asberg Depression Rating Scale score ≥20
- Failed 2+ prior treatments (treatment-refractory)
- May be on current anti-depressant medication at the discretion of PI, if not exceeding doses that would make TMS an increased risk
Who cannot join
- Pregnancy (Female participants)
- MRI contraindication
- Medical condition that interferes with the collection or interpretation of MRI data
- Implanted devices such as: aneurysm clip or cardiac pacemaker
- Diagnosis of stroke, epilepsy, or other neurological disorders interfering with treatment at PI discretion
- Any factor the investigator believe may affect participant safety or compliance (ex: ≥100 miles from clinic)
- Current alcohol or substance use disorder in last 3 months
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Department of Interventional Psychiatry, University of California San Diego
La Jolla, California, 92093
Center for Neuromodulation in Depression and Stress
Philadelphia, Pennsylvania, 19104
About this study
Official title: A Within Study on the Effects of L-dlPFC Activation Through iTBS in Refractory Depression
In this proposal the investigators will use an accelerated TMS protocol that concentrates the magnetic stimulation that would usually occur over 6 weeks into 10 treatment sessions per days, for 5 consecutive days in patient with treatment-refractory depression. This protocol will build on a previously published study demonstrating clinical efficacy of intermittent theta-burst stimulation (iTBS) on left dorsolateral prefrontal cortex (L-dlPFC) in a treatment refractory population.
Read the detailed description
Major depressive disorder (MDD) is a disabling mental disorder with a lifetime prevalence of up to16% . Approximately 30% of MDD patients suffer treatment resistant depression (TRD), with at least 2 failed adequate trials of pharmacotherapy. Repetitive transcranial magnetic stimulation (rTMS) has been shown to be a safe treatment for TRD, yet the standard clinical technique for using it as treatment depressive disorders is associated with limited efficacy to date. Among the potential causes of limited efficacy have been the scalp based targeting technique that is currently the most common targeting method rather than techniques that incorporate functional magnetic resonance imaging (fMRI) neuronavigation, which have been shown to have greater efficacy. Image guided TMS can target specific functional brain networks with greater resolution that takes into account individual differences in brain anatomy.
Another technique for improving treatment efficacy, shown to modulate cortical excitability, may be the application of intermittent theta-burst stimulation in regular intervals, which has been shown to be no different than a longer-in-time application of rTMS. Paired with the evidence that iTBS has produced significant antidepressant responses in severely depressed individuals, and that relapse in depressive states predicts diminished efficacy of treatment as well as increased quantity of TBS pulses to have a beneficial effect, these recent iTBS findings suggest that iTBS may offer a valid treatment alternative to options that have proven otherwise ineffective in treating TRD. Therefore, the investigators aim to administer iTBS to severely-depressed participant in a shorter amount of time, in order to improve their antidepressant outcome.
Significance: This protocol builds on different notions:
- iTBS is not different in treatment outcome than rTMS while applying the same amount of pulses in shorter amount of time;
- The degree of treatment resistance is indicative of iTBS quantity needed to obtain an antidepressant treatment
- Repeated iTBS produces a significant effect in treating refractory depression
- Decreasing the interval between iTBS applications enhanced positive treatment outcomes.
Therefore, the compression of iTBS pulses with shorter intervals between sessions is hypothesized to have an increased beneficial effect on individuals affected by treatment-resistant depression.
- Conditions
- Treatment Resistant Depression
- Being tested
- intermittent Theta Burst Stimulation
- Keywords
- TMS, fMRI
- 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.
intermittent Theta Burst StimulationDevice
The present study will utilize TMS dosage of iTBS of 18 000 pulses a day for 5 consecutive days.
| Study group | Role | What they receive |
|---|---|---|
| Compressed iTBS schedule | Other | Stimulation 3-pulse 50-Hz bursts at 5-Hz for 2-s trains, with trains every 10 s, for 10 minutes, 10 times a day, for 5 consecutive days. Receives: Device: intermittent Theta Burst Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Depressive Symptoms Change
Depressive symptoms will be measured before and after treatment by means of the clinician-administered Montgomery Asberg Depression Rating Scale (MADRS) (0-60, lower scores indicate lower depressive symptoms) and the self report Beck Depression Inventory (BDI II) (0-30, lower scores indicate lower depressive symptoms). Change will be measured by comparing measurements pre- and post- on the same measures. The bigger the change, the bigger the reduction in depressive symptoms.
Measured: 2 Weeks
Secondary outcomes (1)
Self report Symptom Change
Depressive symptoms will be measured before and after treatment by means of the self report Beck Depression Inventory (BDI II) (0-30, lower scores indicate lower depressive symptoms). Change will be measured by comparing measurements pre- and post- on the same measures. The bigger the change, the bigger the reduction in depressive symptoms.
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2020
- Study start20 Feb 2020
- Primary completion30 Nov 2026 (estimated)
- Study completion20 Jan 2027 (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 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
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yvette Sheline, University of Pennsylvania
- Investigators
- Yvette Sheline, MD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04684706
- Sponsor's protocol ID
- 834723
- Acronym
- ciTBS
- Status last verified
- Jan 2026
- First submitted
- 12 Oct 2020
- Last updated
- 16 Jan 2026
- Results posted
- 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 16 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Within Study on the Effects of L-dlPFC Activation Through iTBS in Refractory Depression
- ClinicalTrials.gov ID
- NCT04684706
- Acronym / sponsor ID
- ciTBS / 834723
- Conditions
- Treatment Resistant Depression
- Keywords
- TMS, fMRI
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 20 Feb 2020 (actual)
- Primary completion
- 30 Nov 2026 (estimated)
- Study completion
- 20 Jan 2027 (estimated)
- First posted
- 24 Dec 2020 (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.
In this proposal the investigators will use an accelerated TMS protocol that concentrates the magnetic stimulation that would usually occur over 6 weeks into 10 treatment sessions per days, for 5 consecutive days in patient with treatment-refractory depression. This protocol will build on a previously published study demonstrating clinical efficacy of intermittent theta-burst stimulation (iTBS) on left dorsolateral prefrontal cortex (L-dlPFC) in a treatment refractory population.
Detailed description
Major depressive disorder (MDD) is a disabling mental disorder with a lifetime prevalence of up to16% . Approximately 30% of MDD patients suffer treatment resistant depression (TRD), with at least 2 failed adequate trials of pharmacotherapy. Repetitive transcranial magnetic stimulation (rTMS) has been shown to be a safe treatment for TRD, yet the standard clinical technique for using it as treatment depressive disorders is associated with limited efficacy to date. Among the potential causes of limited efficacy have been the scalp based targeting technique that is currently the most common targeting method rather than techniques that incorporate functional magnetic resonance imaging (fMRI) neuronavigation, which have been shown to have greater efficacy. Image guided TMS can target specific functional brain networks with greater resolution that takes into account individual differences in brain anatomy.
Another technique for improving treatment efficacy, shown to modulate cortical excitability, may be the application of intermittent theta-burst stimulation in regular intervals, which has been shown to be no different than a longer-in-time application of rTMS. Paired with the evidence that iTBS has produced significant antidepressant responses in severely depressed individuals, and that relapse in depressive states predicts diminished efficacy of treatment as well as increased quantity of TBS pulses to have a beneficial effect, these recent iTBS findings suggest that iTBS may offer a valid treatment alternative to options that have proven otherwise ineffective in treating TRD. Therefore, the investigators aim to administer iTBS to severely-depressed participant in a shorter amount of time, in order to improve their antidepressant outcome.
Significance: This protocol builds on different notions:
- iTBS is not different in treatment outcome than rTMS while applying the same amount of pulses in shorter amount of time;
- The degree of treatment resistance is indicative of iTBS quantity needed to obtain an antidepressant treatment
- Repeated iTBS produces a significant effect in treating refractory depression
- Decreasing the interval between iTBS applications enhanced positive treatment outcomes.
Therefore, the compression of iTBS pulses with shorter intervals between sessions is hypothesized to have an increased beneficial effect on individuals affected by treatment-resistant depression.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Compressed iTBS schedule | Other | Device: intermittent Theta Burst StimulationStimulation 3-pulse 50-Hz bursts at 5-Hz for 2-s trains, with trains every 10 s, for 10 minutes, 10 times a day, for 5 consecutive days. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Gender, inclusive
- 18 - 70 years of age
- Meets Diagnostic and Statistical Manual of Mental Disorders criteria for primary diagnosis of MDD
- Patients must be fluent in English
- Participants must have the ability to provide consent
Key exclusion criteria (7 listed)
- Pregnancy (Female participants)
- MRI contraindication
- Medical condition that interferes with the collection or interpretation of MRI data
- Implanted devices such as: aneurysm clip or cardiac pacemaker
- Diagnosis of stroke, epilepsy, or other neurological disorders interfering with treatment at PI discretion
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 |
|---|---|---|
| intermittent Theta Burst StimulationThe present study will utilize TMS dosage of iTBS of 18 000 pulses a day for 5 consecutive days. | Device | Compressed iTBS schedule |
Primary outcome
Depressive Symptoms Change
Time frame: 2 Weeks
Depressive symptoms will be measured before and after treatment by means of the clinician-administered Montgomery Asberg Depression Rating Scale (MADRS) (0-60, lower scores indicate lower depressive symptoms) and the self report Beck Depression Inventory (BDI II) (0-30, lower scores indicate lower depressive symptoms). Change will be measured by comparing measurements pre- and post- on the same measures. The bigger the change, the bigger the reduction in depressive symptoms.
1 secondary outcome
Self report Symptom Change
Time frame: 2 weeks
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 16 Jan 2026.
- 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.
Yvette Sheline, MD principal investigator
University of Pennsylvania
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing intermittent Theta Burst Stimulation in people with Treatment Resistant Depression, run by University of Pennsylvania at 2 sites 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 8 inclusion and 7 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 16 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
Depressive Symptoms Change (time frame: 2 Weeks). 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 16 Jan 2026; AzTrials last refreshed its copy on 2 Nov 2026.