RuminationNCT05437705
Decoding and Modulating Affective Brain States
A study testing Transcranial Magnetic Stimulation in people with Rumination and Major Depressive Disorder, run by University of Pennsylvania at 1 site in United States.
Trial summary
The research study is being conducted to study brain patterns of negative emotion and develop personalized brain stimulation protocols to disrupt these patterns with transcranial magnetic stimulation (TMS). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Rumination, Major Depressive Disorder, Anxiety
- 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
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Feb 2023to 1 Dec 2029
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18-65 years old
- Patient Health Questionnaire (PHQ-9 score) = or > than 10
- Comprehension of instructions in the English language.
- Capacity to provide informed consent and follow study procedures.
- Availability for the duration of the study.
Who cannot join
- Diagnosis of bipolar disorder (as PI discretion), schizophrenia or other psychotic disorder
- Recent use of psychoactive medications or substances as determined by investigators
- History of neurological disorder or traumatic brain injury (other than mild)
- Unable to have an MRI scan, or current or prior medical condition that could interfere with the collection or interpretation of MRI data
- Unable to receive or tolerate TMS
- Implanted devices, such as an aneurysm clip or cardiac pacemaker
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- History of stroke, epilepsy, or brain scarring
- Pregnant, nursing, or trying to become pregnant (self-attestation alone)
- During this study, participants are asked to:
- Refrain from substance use (including marijuana and illicit drugs) for duration of the study (self-attestation alone).
- Abstain from alcohol for 24 hours before the MRI scans (self-attestation alone).
- Abstain from increasing caffeine intake or begin taking any new medications (self-attestation alone).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Camille Blaine, 215-573-0828, camille.blaine@pennmedicine.upenn.edu
Almaris Figueroa-Gonzalez, 215-746-6751, almaris.figueroa-gonzalez@pennmedicine.upenn.edu
About this study
The research study is being conducted to study brain patterns of negative emotion and develop personalized brain stimulation protocols to disrupt these patterns with transcranial magnetic stimulation (TMS). First, the investigators will use functional Magnetic Resonance Imaging (fMRI) data to generate a negative affect map for each participant. Then, the investigators will apply a variety of repetitive transcranial magnetic stimulation (rTMS) sequences while the participant is inside the MRI scanner to determine the optimal and least optimal rTMS frequencies at changing negative affect brain states. Finally, these two frequencies will be tested over two 3-day rTMS neuromodulation sessions to assess whether they can reduce negative emotions.
Read the detailed description
The study involves 11 visits over approximately 10 weeks, depending on scanner availability and scheduling. See below for the study schedule with a summary of the procedures:
- Visit 1: Screening Procedures (~3-4 hours). The first part of the screening will take place remotely (~1 hour). The investigators will begin by reviewing the Informed Consent Form (ICF). Participants who agree to participate and sign the ICF will then complete several questionnaires. Those who meet preliminary eligibility criteria based on the remote procedures will be invited for an in-person visit. The in-person screening will include a brief TMS demonstration (~20 minutes). If TMS is well tolerated, the visit will proceed to a comprehensive clinical interview (~2-3 hours) to assess current and past mental health history.
- Visit 2: Baseline MRI \& Assessments (~2 hours). This visit will involve a 1-hour MRI scan, including both structural and functional sequences, and an assessment session with computerized tasks and questionnaires.
- Visit 3: MRI Scan with TMS (~2.5 hours). A second MRI scan will be conducted with concurrent TMS procedures. Participants will complete a mental task while interleaved rTMS is delivered at different frequencies. This scan will be used to determine the optimal stimulation frequency for each participant.
- Visits 4-6: First Neuromodulation Session (~1.5 hours each). Participants will receive rTMS using either the optimal or least optimal stimulation frequency. They will also complete two computerized tasks after rTMS, with questionnaires in between procedures.
- Visit 7: MRI Scan with TMS (~2 hours). This visit will be a shortened version of Visit 3, as some MRI scans and questionnaires will not need to be repeated.
- Visits 8-10: Second Neuromodulation Session (~1.5 hours each). These visits will mirror Visits 4-6. However, the TMS condition administered (optimal or suboptimal frequency) will be counterbalanced with the condition used during the first neuromodulation session. Visit 8 will be scheduled at least 2 weeks after Visit 7.
- Visit 11: MRI Scan with TMS (~2 hours). This visit will mirror Visit 7.
After completing all procedures, participants will receive the full study compensation. Payments may be issued earlier if participants request compensation after each visit or if they withdraw early.
- Conditions
- Rumination, Major Depressive Disorder, Anxiety
- Being tested
- Transcranial Magnetic Stimulation
- Keywords
- TMS, rumination, depression, anxiety
- Medical subject headings
- Rumination Syndrome, Depressive Disorder, Major, Anxiety Disorders, 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. The MagPro X100* magnetic stimulator and Cool-B65 Butterfly Coil are FDA-approved for rTMS treatments of depression.
| Study group | Role | What they receive |
|---|---|---|
| Neuromodulation using the optimal rTMS stimulation frequency | Experimental | Through manipulation of brain state with a negative-affect task and using fMRI as the feedback signal, the investigators aim to fine-tune repetitive Transcranial Magnetic Stimulation (rTMS) delivery to maximally impact the desired brain states in awake, behaving participants in a highly individualized manner (Visit 3). The optimal rTMS stimulation frequency will then be tested in a 3-day rTMS neuromodulation intervention. Receives: Device: Transcranial Magnetic Stimulation |
| Neuromodulation using the least optimal rTMS stimulation frequency | Active comparator | The investigators will compare the results of the optimal rTMS frequency neuromodulation with a separate 3-day neuromodulation session using the least optimal rTMS frequency, as determined by the results of Visit 3. Receives: Device: Transcranial Magnetic Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in ruminative response scale (RRS) score after using the optimal rTMS stimulation frequency vs the least optimal rTMS stimulation frequency
By comparing the RRS score change pre/post rTMS of both neuromodulation sessions (Visits 4-6/7-9) the investigators will determine whether the optimal rTMS stimulation frequency is more effective at improving clinical outcomes.
Measured: Up to 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2022
- Study start21 Feb 2023
- Primary completion1 Dec 2028 (estimated)
- Study completion1 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for RuminationStudies 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
- Randomised
- Intervention model
- Crossover
- Model description
- All subjects will receive TMS using the optimized and least optimized frequencies, but the order is randomized and counterbalanced.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 40 participants (estimated)
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, Associate Professor of Psychiatry
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05437705
- Sponsor's protocol ID
- 850664
- Status last verified
- Sep 2026
- First submitted
- 13 Jun 2022
- Last updated
- 3 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Decoding and Modulating Affective Brain States
- ClinicalTrials.gov ID
- NCT05437705
- Acronym / sponsor ID
- 850664
- Conditions
- Rumination, Major Depressive Disorder, Anxiety
- Keywords
- TMS, rumination, depression, anxiety
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 21 Feb 2023 (actual)
- Primary completion
- 1 Dec 2028 (estimated)
- Study completion
- 1 Dec 2029 (estimated)
- First posted
- 29 Jun 2022 (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.
The research study is being conducted to study brain patterns of negative emotion and develop personalized brain stimulation protocols to disrupt these patterns with transcranial magnetic stimulation (TMS). First, the investigators will use functional Magnetic Resonance Imaging (fMRI) data to generate a negative affect map for each participant. Then, the investigators will apply a variety of repetitive transcranial magnetic stimulation (rTMS) sequences while the participant is inside the MRI scanner to determine the optimal and least optimal rTMS frequencies at changing negative affect brain states. Finally, these two frequencies will be tested over two 3-day rTMS neuromodulation sessions to assess whether they can reduce negative emotions.
Detailed description
The study involves 11 visits over approximately 10 weeks, depending on scanner availability and scheduling. See below for the study schedule with a summary of the procedures:
- Visit 1: Screening Procedures (~3-4 hours). The first part of the screening will take place remotely (~1 hour). The investigators will begin by reviewing the Informed Consent Form (ICF). Participants who agree to participate and sign the ICF will then complete several questionnaires. Those who meet preliminary eligibility criteria based on the remote procedures will be invited for an in-person visit. The in-person screening will include a brief TMS demonstration (~20 minutes). If TMS is well tolerated, the visit will proceed to a comprehensive clinical interview (~2-3 hours) to assess current and past mental health history.
- Visit 2: Baseline MRI \& Assessments (~2 hours). This visit will involve a 1-hour MRI scan, including both structural and functional sequences, and an assessment session with computerized tasks and questionnaires.
- Visit 3: MRI Scan with TMS (~2.5 hours). A second MRI scan will be conducted with concurrent TMS procedures. Participants will complete a mental task while interleaved rTMS is delivered at different frequencies. This scan will be used to determine the optimal stimulation frequency for each participant.
- Visits 4-6: First Neuromodulation Session (~1.5 hours each). Participants will receive rTMS using either the optimal or least optimal stimulation frequency. They will also complete two computerized tasks after rTMS, with questionnaires in between procedures.
- Visit 7: MRI Scan with TMS (~2 hours). This visit will be a shortened version of Visit 3, as some MRI scans and questionnaires will not need to be repeated.
- Visits 8-10: Second Neuromodulation Session (~1.5 hours each). These visits will mirror Visits 4-6. However, the TMS condition administered (optimal or suboptimal frequency) will be counterbalanced with the condition used during the first neuromodulation session. Visit 8 will be scheduled at least 2 weeks after Visit 7.
- Visit 11: MRI Scan with TMS (~2 hours). This visit will mirror Visit 7.
After completing all procedures, participants will receive the full study compensation. Payments may be issued earlier if participants request compensation after each visit or if they withdraw early.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- All subjects will receive TMS using the optimized and least optimized frequencies, but the order is randomized and counterbalanced.
| Arm | Type | Receives |
|---|---|---|
| Neuromodulation using the optimal rTMS stimulation frequency | Experimental | Device: Transcranial Magnetic StimulationThrough manipulation of brain state with a negative-affect task and using fMRI as the feedback signal, the investigators aim to fine-tune repetitive Transcranial Magnetic Stimulation (rTMS) delivery to maximally impact the desired brain states in awake, behaving participants in a highly individualized manner (Visit 3). The optimal rTMS stimulation frequency will then be tested in a 3-day rTMS neuromodulation intervention. |
| Neuromodulation using the least optimal rTMS stimulation frequency | Active comparator | Device: Transcranial Magnetic StimulationThe investigators will compare the results of the optimal rTMS frequency neuromodulation with a separate 3-day neuromodulation session using the least optimal rTMS frequency, as determined by the results of Visit 3. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 18-65 years old
- Patient Health Questionnaire (PHQ-9 score) = or > than 10
- Comprehension of instructions in the English language.
- Capacity to provide informed consent and follow study procedures.
- Availability for the duration of the study.
Key exclusion criteria (12 listed)
- Diagnosis of bipolar disorder (as PI discretion), schizophrenia or other psychotic disorder
- Recent use of psychoactive medications or substances as determined by investigators
- History of neurological disorder or traumatic brain injury (other than mild)
- Unable to have an MRI scan, or current or prior medical condition that could interfere with the collection or interpretation of MRI data
- Unable to receive or tolerate TMS
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. The MagPro X100* magnetic stimulator and Cool-B65 Butterfly Coil are FDA-approved for rTMS treatments of depression. | Device | Neuromodulation using the least optimal rTMS stimulation frequency, Neuromodulation using the optimal rTMS stimulation frequency |
Primary outcome
Change in ruminative response scale (RRS) score after using the optimal rTMS stimulation frequency vs the least optimal rTMS stimulation frequency
Time frame: Up to 4 weeks
By comparing the RRS score change pre/post rTMS of both neuromodulation sessions (Visits 4-6/7-9) the investigators will determine whether the optimal rTMS stimulation frequency is more effective at improving clinical outcomes.
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 3 Sep 2026.
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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.
Desmond Oathes, PhD principal investigator
Associate Professor of Psychiatry
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 Rumination and 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 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: looking for participants now, as of the sponsor's last update on 3 Sep 2026. 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?
Contact Camille Blaine (215-573-0828, camille.blaine@pennmedicine.upenn.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in ruminative response scale (RRS) score after using the optimal rTMS stimulation frequency vs the least optimal rTMS stimulation frequency (time frame: Up to 4 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 3 Sep 2026.