Major Depressive Disorder (MDD)NCT07159061
Neurofeedback to Treat Depression - 2
A study testing Active Closed Loop Real Time fMRI Neurofeedback in people with Major Depressive Disorder (MDD), run by University of Pennsylvania at 1 site in United States.
Trial summary
This study tests the efficacy of a new psychotherapeutic strategy for reducing negative attention bias (and therefore depression severity) in participants with MDD. This real-time fMRI neurofeedback therapy uses cloud-based pattern classification to decode a patient's attentional state and dynamically modulate task… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorder (MDD)
- What is being tested?
- Active Closed Loop Real Time fMRI Neurofeedback
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Nov 2025to 1 Dec 2028
- 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
- Gender, inclusive
- Adult aged 18 - 65
- Meets Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for MDD according to the Clinician-Administered MDD Scale for DSM-5 (unipolar depression or bipolar II depressed)
- Scores at least a minimum score of 16 on Montgomery Asberg Depression Rating Scale (MADRS)
- Normal cognition
- Participants must be able to read and understand English
- Participants must be able to provide consent
Who cannot join
- Pregnancy (female participants)
- Outside age range
- MRI contraindications (medical implant, claustrophobia, etc.)
- Use of psychoactive medication (including antidepressants) or currently in therapy
- Neurological disorder or any condition that in the view of the PI could impact brain data, cause depression, require medication that could cause depressive symptoms, or otherwise result in participant being unfit for study (for example, co-morbid psychotic, neurological disorders, developmentally or cognitively disabled/impaired, active alcohol or drug abuse/dependence within the past 6 months).
- Non-English speaking
Show all 9Show fewer
- Non-correctable vision loss
- Refusal to provide informed consent
- representing an active suicide risk
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
Center for Neuromodulation in Depression and Stress
Philadelphia, Pennsylvania, 19104
Maria Prociuk, (215) 573-4229, lmari@pennmedicine.upenn.edu
Yvette Sheline, MD
About this study
Official title: Reducing Neural Perseveration Through Closed Loop Real Time fMRI Neurofeedback to Alleviate Depressive Symptoms
This study tests the efficacy of a new psychotherapeutic strategy for reducing negative attention bias (and therefore depression severity) in participants with MDD. This real-time fMRI neurofeedback therapy uses cloud-based pattern classification to decode a patient's attentional state and dynamically modulate task stimuli (in a closed loop) based on this state.
Read the detailed description
The investigators will compare cloud based real time fMRI feedback with placebo (sham feedback) in reducing negative attention bias and depressive symptoms. This study will be the first dose-finding test of real-time fMRI effect on negative attention bias. Measures include: Structured Clinical Interview for DSM-5 (SCID), Clinician-administered diagnostic exam, Montgomery Asberg Depression Rating Scale (MADRS), Clinician-administered scale used to assess the severity of depression, State-Trait Anxiety Inventory (STAI), Self-report questionnaire used to measure types of anxiety and mood symptoms, Mood and Anxiety Symptom Questionnaire (MASQ), Negative perseveration during a go/no-go task, Go/no-go task with overlaid face/scene stimuli; brain response triggers next stimulus, Negative gaze, Negative gaze collected in gaze data following each real time fMRI feedback session
- Conditions
- Major Depressive Disorder (MDD)
- Being tested
- Active Closed Loop Real Time fMRI Neurofeedback, Sham Closed Loop Real Time fMRI Neurofeedback
- 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.
Active Closed Loop Real Time fMRI NeurofeedbackBehavioural
Active neurofeedback to target neural mechanisms underlying attentional bias in participants with major depressive discover (MDD)
Sham Closed Loop Real Time fMRI NeurofeedbackBehavioural
Sham (placebo) neurofeedback to target neural mechanisms underlying attentional bias in participants with major depressive discover (MDD)
| Study group | Role | What they receive |
|---|---|---|
| Active Comparator: Active Neurofeedback | Active comparator | R33 Phase: Three training sessions. Each training session contains 32 minutes of active neurofeedback runs. Receives: Behavioral: Active Closed Loop Real Time fMRI Neurofeedback |
| Sham Comparator: Sham Neurofeedback | Sham comparator | R33 Phase: Three training sessions. Each training session contains 32 minutes of sham (placebo) neurofeedback runs. Receives: Behavioral: Sham Closed Loop Real Time fMRI Neurofeedback |
What is being measured
The primary outcome is the main question the study is designed to answer.
Montgomery Asberg Depression Rating Scale (MADRS)
Clinician administered scale to assess the severity of depression. MADRS scores will be compare the effect of real-time neurofeedback vs sham neurofeedback on depression outcome in patients with MDD. A MADRS score of 16 or higher is needed in order to be eligible to be enrolled in the study. The higher the MADRS score, the more depressed the individual will be. A lower MADRS score indicates that the individual's depressive symptoms have improved. A higher MADRS score indicates that the individual's depressive symptoms have worsened.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2025
- Study start21 Nov 2025
- Primary completion21 Nov 2028 (estimated)
- Study completion1 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive Disorder (MDD)Studies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 80 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, M.D., Principal investigator, Center for Neuromodulation in Depression and Stress, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07159061
- Sponsor's protocol ID
- 849298-2
- Status last verified
- Dec 2025
- First submitted
- 3 Sep 2025
- Last updated
- 4 Dec 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Data will only be shared amongst the study sites.
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reducing Neural Perseveration Through Closed Loop Real Time fMRI Neurofeedback to Alleviate Depressive Symptoms
- ClinicalTrials.gov ID
- NCT07159061
- Acronym / sponsor ID
- 849298-2
- Conditions
- Major Depressive Disorder (MDD)
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 21 Nov 2025 (actual)
- Primary completion
- 21 Nov 2028 (estimated)
- Study completion
- 1 Dec 2028 (estimated)
- First posted
- 8 Sep 2025 (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 tests the efficacy of a new psychotherapeutic strategy for reducing negative attention bias (and therefore depression severity) in participants with MDD. This real-time fMRI neurofeedback therapy uses cloud-based pattern classification to decode a patient's attentional state and dynamically modulate task stimuli (in a closed loop) based on this state.
Detailed description
The investigators will compare cloud based real time fMRI feedback with placebo (sham feedback) in reducing negative attention bias and depressive symptoms. This study will be the first dose-finding test of real-time fMRI effect on negative attention bias. Measures include: Structured Clinical Interview for DSM-5 (SCID), Clinician-administered diagnostic exam, Montgomery Asberg Depression Rating Scale (MADRS), Clinician-administered scale used to assess the severity of depression, State-Trait Anxiety Inventory (STAI), Self-report questionnaire used to measure types of anxiety and mood symptoms, Mood and Anxiety Symptom Questionnaire (MASQ), Negative perseveration during a go/no-go task, Go/no-go task with overlaid face/scene stimuli; brain response triggers next stimulus, Negative gaze, Negative gaze collected in gaze data following each real time fMRI feedback session
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active Comparator: Active Neurofeedback | Active comparator | Behavioral: Active Closed Loop Real Time fMRI NeurofeedbackR33 Phase: Three training sessions. Each training session contains 32 minutes of active neurofeedback runs. |
| Sham Comparator: Sham Neurofeedback | Sham comparator | Behavioral: Sham Closed Loop Real Time fMRI NeurofeedbackR33 Phase: Three training sessions. Each training session contains 32 minutes of sham (placebo) neurofeedback runs. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Gender, inclusive
- Adult aged 18 - 65
- Meets Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for MDD according to the Clinician-Administered MDD Scale for DSM-5 (unipolar depression or bipolar II depressed)
- Scores at least a minimum score of 16 on Montgomery Asberg Depression Rating Scale (MADRS)
- Normal cognition
Key exclusion criteria (9 listed)
- Pregnancy (female participants)
- Outside age range
- MRI contraindications (medical implant, claustrophobia, etc.)
- Use of psychoactive medication (including antidepressants) or currently in therapy
- Neurological disorder or any condition that in the view of the PI could impact brain data, cause depression, require medication that could cause depressive symptoms, or otherwise result in participant being unfit for study (for example, co-morbid psychotic, neurological disorders, developmentally or cognitively disabled/impaired, active alcohol or drug abuse/dependence within the past 6 months).
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 Closed Loop Real Time fMRI NeurofeedbackActive neurofeedback to target neural mechanisms underlying attentional bias in participants with major depressive discover (MDD) | Behavioural | Active Comparator: Active Neurofeedback |
| Sham Closed Loop Real Time fMRI NeurofeedbackSham (placebo) neurofeedback to target neural mechanisms underlying attentional bias in participants with major depressive discover (MDD) | Behavioural | Sham Comparator: Sham Neurofeedback |
Primary outcome
Montgomery Asberg Depression Rating Scale (MADRS)
Time frame: 3 months
Clinician administered scale to assess the severity of depression. MADRS scores will be compare the effect of real-time neurofeedback vs sham neurofeedback on depression outcome in patients with MDD. A MADRS score of 16 or higher is needed in order to be eligible to be enrolled in the study. The higher the MADRS score, the more depressed the individual will be. A lower MADRS score indicates that the individual's depressive symptoms have improved. A higher MADRS score indicates that the individual's depressive symptoms have worsened.
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 Dec 2025.
- Individual participant dataSharing planned: No. Data will only be shared amongst the study sites.
Related trials for Major Depressive Disorder (MDD)
RecruitingPhase 1
Open-Label Psilocybin Study in Transdiagnostic Population
Transdiagnostic, Depression - Major Depressive Disorder
Not yet recruitingPhase 2
Assessing of Behavioral Risk and Response to Electromagnetic and Psychedelic Therapies
PTSD, PTSD - Post Traumatic Stress Disorder
RecruitingPhase 2
A Study to Evaluate TNX-102 SL Monotherapy Versus Placebo in Participants With Major Depressive Disorder (MDD)
Major Depressive Episode (MDE), Major Depressive Disorder (MDD)
RecruitingPhase 1
Mechanism of Action Underlying Ketamine's Antidepressant Effects: The AMPA Throughput Theory in Patients With Treatment-Resistant Major Depression
Depression, Major Depressive Disorder
Not yet recruiting
Acceptance and Committment Therapy Combined With Ketamine in Difficult-to-Treat Depression.
Major Depressive Disorder (MDD)
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.
Yvette Sheline, M.D. principal investigator
Center for Neuromodulation in Depression and Stress, 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 Active Closed Loop Real Time fMRI Neurofeedback in people with Major Depressive Disorder (MDD), 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 7 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: looking for participants now, as of the sponsor's last update on 4 Dec 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. 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?
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 Yvette Sheline, M.D. ((215) 746-2637, cndslab@pennmedicine.upenn.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Montgomery Asberg Depression Rating Scale (MADRS) (time frame: 3 months). 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 Dec 2025.