Major Depressive DisorderNCT05703256
Amygdala Neurofeedback for Depression - Large Scale Clinical Trial
A study testing Amygdala real-time fMRI neurofeedback in people with Major Depressive Disorder, run by Kymberly Young at 1 site in United States.
Trial summary
The goal of this study is to evaluate whether rtfMRI-nf training to increase the amygdala response to positive memories may serve as a stand-alone intervention for major depressive disorder Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Amygdala real-time fMRI neurofeedback
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2023to 30 Apr 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 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- ages 18 - 55
- primary diagnosis of MDD and are currently depressed
- able to give written informed consent prior to participation
- unmedicated OR are stable on an antidepressant regime (at least 4 weeks to ensure symptoms are stable). Effective medications will not be discontinued for the purposes of the study.
Who cannot join
- clinically significant or unstable cardiovascular, pulmonary, endocrine, neurological, gastrointestinal illness or unstable medical disorder
- Current severe DSM-V alcohol or substance use disorder, with the exception of nicotine or caffeine. Clinician will access subjects' alcohol and substance use on a case-by-case to determine whether specific cases of mild or moderate alcohol or substance use would also interfere with the effects of the intervention.
- history of traumatic brain injury
- unable to complete MRI scan due to claustrophobia or general MRI exclusions (e.g., shrapnel inside body)
- currently pregnant or breast feeding
- unable to complete questionnaires written in English
Show all 9Show fewer
- current (within 3 weeks of testing) use of any antipsychotics, anticonvulsants, stimulants, benzodiazepines, beta-blockers, or other medications (except antidepressants) likely to influence cerebral blood flow. Effective medications will not be discontinued for the purposes of the study.
- diagnosis of psychotic or organic mental disorder, bipolar I or II disorder.
- eye problems or difficulties in corrected vision.
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 Pittsburgh
Pittsburgh, Pennsylvania, 15261
Kymberly Young, PhD, youngk@pitt.edu
About this study
Official title: Confirmatory Efficacy Randomized Clinical Trial of Amygdala Neurofeedback for Major Depressive Disorder
The goal of this study is to evaluate whether rtfMRI-nf training to increase the amygdala response to positive memories may serve as a stand-alone intervention for major depressive disorder
Read the detailed description
Previous research has shown that real-time fMRI neurofeedback (rtfMRI-nf) training aimed at increasing the amygdala's response to positive autobiographical memory recall holds therapeutic potential for treating patients with major depressive disorder (MDD), as clinically significant decreases in clinician administered and self-report measures of depression severity were observed following two rtfMRI amygdala neurofeedback sessions. Furthermore, rtfMRI amygdala neurofeedback changed emotional processing towards a positive bias. The goal of the current study is to confirm the clinical efficacy of this intervention in a new sample of depressed participants. Thus, over the course of four years, we will conduct a randomized double-blind clinical trial examining the clinical and cognitive effects of amygdala rtfMRI-nf compared to yoked sham rtfMRI-nf (seeing the amygdala activity of another participant during training) in 200 participants with MDD from the Pittsburgh metropolitan area. Participants will undergo two rtfMRI-nf sessions. Half of the participants will receive amygdala neurofeedback and half will receive yoked sham neurofeedback. Participants will complete the BDI-II monthly for one year following completion of the neurofeedback intervention. The rationale for the proposed research is to provide new insights into possible mechanistic solutions for MDD, and to further guide development of this rtfMRI-nf intervention into a treatment for MDD.
- Conditions
- Major Depressive Disorder
- Being tested
- Amygdala real-time fMRI neurofeedback, Sham feedback
- Keywords
- neurofeedback, amygdala, depression, major depressive disorder
- 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.
Amygdala real-time fMRI neurofeedbackDevice
Participants are shown activity from their left amygdala in real time and are instructed to increase the level of activity in that region by thinking of positive autobiographical memories
Sham feedbackDevice
Participants are shown activity from another participant's left amygdala who previously completed the task and are instructed to increase the level of activity in that region by thinking of positive autobiographical memories
| Study group | Role | What they receive |
|---|---|---|
| Amygdala real-time fMRI neurofeedback | Experimental | Amygdala neurofeedback - attempt to upregulate the left amygdala during positive autobiographical memory recall via real time fMRI neurofeedback from the amygdala. Two sessions will be performed one week apart. Receives: Device: Amygdala real-time fMRI neurofeedback |
| Sham feedback | Sham comparator | Yoked sham - participants will see the amygdala activity of another subject who completed the intervention. Two sessions will be performed one week apart. Receives: Device: Sham feedback |
What is being measured
The primary outcome is the main question the study is designed to answer.
Beck Depression Inventory (BDI-II)
measures depressive symptoms. The total score will be used, which ranges from 0-63. A total score of 0-13 is considered minimal range, 14-19 is mild, 20-28 is moderate, and 29-63 is severe. Lower values represent better outcomes.
Measured: baseline vs up to one year
Secondary outcomes (1)
Life Functioning Questionnaire (LFQ)
measures ability to function in daily life. The total score will be used, which ranges from 14-56. A total score of 14-27 indicates no problems, and a score of 28+ indicates some impairment. Lower values represent better outcomes.
Measured: baseline vs up to one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2023
- Study start1 Jun 2023
- Primary completion30 Apr 2027 (estimated)
- Study completion30 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- 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
- Model description
- Participants will be randomly assigned to receive amygdala neurofeedback or yoked sham neurofeedback (seeing the amygdala activity of another participant)
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kymberly Young
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor-investigator, Kymberly Young, University of Pittsburgh
- Investigators
- Kymberly Young, PhD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05703256
- Sponsor's protocol ID
- STUDY23010004
- Other IDs
- R01MH130337
- Status last verified
- Mar 2026
- First submitted
- 18 Jan 2023
- Last updated
- 4 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: All fMRI, BDI and LFQ scores for IPD will be made available through the NDAR data repository
Publications
Young KD, Zotev V, Phillips R, Misaki M, Yuan H, Drevets WC, Bodurka J. Real-time FMRI neurofeedback training of amygdala activity in patients with major depressive disorder. PLoS One. 2014 Feb 11;9(2):e88785. doi: 10.1371/journal.pone.0088785. eCollection 2014.
PubMed 24523939Young KD, Siegle GJ, Zotev V, Phillips R, Misaki M, Yuan H, Drevets WC, Bodurka J. Randomized Clinical Trial of Real-Time fMRI Amygdala Neurofeedback for Major Depressive Disorder: Effects on Symptoms and Autobiographical Memory Recall. Am J Psychiatry. 2017 Aug 1;174(8):748-755. doi: 10.1176/appi.ajp.2017.16060637. Epub 2017 Apr 14.
PubMed 28407727Young KD, Misaki M, Harmer CJ, Victor T, Zotev V, Phillips R, Siegle GJ, Drevets WC, Bodurka J. Real-Time Functional Magnetic Resonance Imaging Amygdala Neurofeedback Changes Positive Information Processing in Major Depressive Disorder. Biol Psychiatry. 2017 Oct 15;82(8):578-586. doi: 10.1016/j.biopsych.2017.03.013. Epub 2017 Mar 28.
PubMed 28476207
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Confirmatory Efficacy Randomized Clinical Trial of Amygdala Neurofeedback for Major Depressive Disorder
- ClinicalTrials.gov ID
- NCT05703256
- Acronym / sponsor ID
- STUDY23010004
- Conditions
- Major Depressive Disorder
- Keywords
- neurofeedback, amygdala, depression, major depressive disorder
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Kymberly YoungUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 1 Jun 2023 (actual)
- Primary completion
- 30 Apr 2027 (estimated)
- Study completion
- 30 Apr 2028 (estimated)
- First posted
- 30 Jan 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.
The goal of this study is to evaluate whether rtfMRI-nf training to increase the amygdala response to positive memories may serve as a stand-alone intervention for major depressive disorder
Detailed description
Previous research has shown that real-time fMRI neurofeedback (rtfMRI-nf) training aimed at increasing the amygdala's response to positive autobiographical memory recall holds therapeutic potential for treating patients with major depressive disorder (MDD), as clinically significant decreases in clinician administered and self-report measures of depression severity were observed following two rtfMRI amygdala neurofeedback sessions. Furthermore, rtfMRI amygdala neurofeedback changed emotional processing towards a positive bias. The goal of the current study is to confirm the clinical efficacy of this intervention in a new sample of depressed participants. Thus, over the course of four years, we will conduct a randomized double-blind clinical trial examining the clinical and cognitive effects of amygdala rtfMRI-nf compared to yoked sham rtfMRI-nf (seeing the amygdala activity of another participant during training) in 200 participants with MDD from the Pittsburgh metropolitan area. Participants will undergo two rtfMRI-nf sessions. Half of the participants will receive amygdala neurofeedback and half will receive yoked sham neurofeedback. Participants will complete the BDI-II monthly for one year following completion of the neurofeedback intervention. The rationale for the proposed research is to provide new insights into possible mechanistic solutions for MDD, and to further guide development of this rtfMRI-nf intervention into a treatment for MDD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- Participants will be randomly assigned to receive amygdala neurofeedback or yoked sham neurofeedback (seeing the amygdala activity of another participant)
| Arm | Type | Receives |
|---|---|---|
| Amygdala real-time fMRI neurofeedback | Experimental | Device: Amygdala real-time fMRI neurofeedbackAmygdala neurofeedback - attempt to upregulate the left amygdala during positive autobiographical memory recall via real time fMRI neurofeedback from the amygdala. Two sessions will be performed one week apart. |
| Sham feedback | Sham comparator | Device: Sham feedbackYoked sham - participants will see the amygdala activity of another subject who completed the intervention. Two sessions will be performed one week apart. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- ages 18 - 55
- primary diagnosis of MDD and are currently depressed
- able to give written informed consent prior to participation
- unmedicated OR are stable on an antidepressant regime (at least 4 weeks to ensure symptoms are stable). Effective medications will not be discontinued for the purposes of the study.
Key exclusion criteria (9 listed)
- clinically significant or unstable cardiovascular, pulmonary, endocrine, neurological, gastrointestinal illness or unstable medical disorder
- Current severe DSM-V alcohol or substance use disorder, with the exception of nicotine or caffeine. Clinician will access subjects' alcohol and substance use on a case-by-case to determine whether specific cases of mild or moderate alcohol or substance use would also interfere with the effects of the intervention.
- history of traumatic brain injury
- unable to complete MRI scan due to claustrophobia or general MRI exclusions (e.g., shrapnel inside body)
- currently pregnant or breast feeding
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 |
|---|---|---|
| Amygdala real-time fMRI neurofeedbackParticipants are shown activity from their left amygdala in real time and are instructed to increase the level of activity in that region by thinking of positive autobiographical memories | Device | Amygdala real-time fMRI neurofeedback |
| Sham feedbackParticipants are shown activity from another participant's left amygdala who previously completed the task and are instructed to increase the level of activity in that region by thinking of positive autobiographical memories | Device | Sham feedback |
Primary outcome
Beck Depression Inventory (BDI-II)
Time frame: baseline vs up to one year
measures depressive symptoms. The total score will be used, which ranges from 0-63. A total score of 0-13 is considered minimal range, 14-19 is mild, 20-28 is moderate, and 29-63 is severe. Lower values represent better outcomes.
1 secondary outcome
Life Functioning Questionnaire (LFQ)
Time frame: baseline vs up to one year
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 Mar 2026.
- Background: PubMed 24523939Young KD, Zotev V, Phillips R, Misaki M, Yuan H, Drevets WC, Bodurka J. Real-time FMRI neurofeedback training of amygdala activity in patients with major depressive disorder. PLoS One. 2014 Feb 11;9(2):e88785. doi: 10.1371/journal.pone.0088785. eCollection 2014.
- Background: PubMed 28407727Young KD, Siegle GJ, Zotev V, Phillips R, Misaki M, Yuan H, Drevets WC, Bodurka J. Randomized Clinical Trial of Real-Time fMRI Amygdala Neurofeedback for Major Depressive Disorder: Effects on Symptoms and Autobiographical Memory Recall. Am J Psychiatry. 2017 Aug 1;174(8):748-755. doi: 10.1176/appi.ajp.2017.16060637. Epub 2017 Apr 14.
- Background: PubMed 28476207Young KD, Misaki M, Harmer CJ, Victor T, Zotev V, Phillips R, Siegle GJ, Drevets WC, Bodurka J. Real-Time Functional Magnetic Resonance Imaging Amygdala Neurofeedback Changes Positive Information Processing in Major Depressive Disorder. Biol Psychiatry. 2017 Oct 15;82(8):578-586. doi: 10.1016/j.biopsych.2017.03.013. Epub 2017 Mar 28.
- Individual participant dataSharing planned: Yes. All fMRI, BDI and LFQ scores for IPD will be made available through the NDAR data repository
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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.
Kymberly Young, PhD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Amygdala real-time fMRI neurofeedback in people with Major Depressive Disorder, run by Kymberly Young 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 4 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 Mar 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. 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 Kymberly Young, PhD (412-648-6179, youngk@pitt.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Beck Depression Inventory (BDI-II) (time frame: baseline vs up to one year). 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 NCT05703256, which also lists 3 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 4 Mar 2026.