Major Depressive Disorder (MDD)NCT07694076
Repeated Real-time Biofeedback With 7-Tesla MRI for Treatment of Depression
A study testing Active Biofeedback in people with Major Depressive Disorder (MDD), run by University of Oxford at 1 site in United Kingdom.
Trial summary
Previous work demonstrated that individuals are able to self-regulate their ventral tegmental area (VTA) activity using real-time biofeedback. The current study expands this approach to a larger sample with repeated training sessions to more robustly characterize the effects of VTA modulation. 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 Biofeedback
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jun 2026to Jun 2033
- Phase
- Interventional
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
- Male or female aged 18-65 years;
- Meets DSM-5 criteria for major depressive disorder (MDD) as determined by the Structured Clinical Interview for DSM-5 Axis Disorders (SCID) or the Mini International Neuropsychiatric Interview (MINI); with a current major depressive episode.
- Participants must have a level of understanding of the English language sufficient to agree to all tests and examinations required by the study and must be able to participate fully in the informed consent process.
Who cannot join
- Current or history of schizophrenia or other psychotic disorder, neurodevelopmental disorder, neurocognitive disorder or cognitive impairment
- Active substance use disorder within the past 1 year;
- Any unstable medical illnesses;
- Women who are pregnant;
- Any contraindications to MRI
- Antidepressant medication initiated within 2 weeks of the Baseline Assessment and concomitant use of any other medication with central nervous system activity during active participation;
- Active suicidal intent or plan.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site, 1 recruiting
- Recruiting
Oxford Centre for Integrative Neuroimaging (OxCIN) FMRIB, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital
Oxford, OX39DU
About this study
Previous work demonstrated that individuals are able to self-regulate their ventral tegmental area (VTA) activity using real-time biofeedback. The current study expands this approach to a larger sample with repeated training sessions to more robustly characterize the effects of VTA modulation. The study will assess change in mood and motivation-related measures, as well as neural activity and connectivity changes.
Read the detailed description
Major depressive disorder (MDD) is one of the world's largest health problems with current treatments that are ineffective for a substantial proportion of individuals. There is a critical need for mechanistically informed interventions that are individualized and that aim to target core symptoms.
Converging evidence from animal and human research in the field has implicated the ventral tegmental area (VTA), a key component of the brain's dopamine system, in regulating motivation and reward-related behaviour. Previous work has demonstrated that participants can successfully train to self-regulate their VTA activity using cognitive strategies while receiving real-time feedback. This shows that VTA self-regulation is feasible in humans.
The current study builds on this previous work to further investigate the relationships between VTA activity modulation and mood and motivation related changes in individuals with MDD. Specifically, this study will aim to extend on prior findings by increasing the sample size and incorporating repeated training sessions to enhance and characterize training effects over time. A total of 60 participants with MDD will be recruited and will be randomized in a 1:1 ratio to receive either active biofeedback or sham (control) feedback.
Participants will complete two training sessions with real-time 7T-MRI biofeedback. During functional MRI (fMRI) scanning, participants will be trained to use self-generated cognitive strategies to modulate their VTA activity while viewing a visual representation of their brain signal (active condition) or a yoked control signal (sham condition).
The primary objective of this study is to determine how VTA modulation influences mood and motivation related measures over time. Secondary objectives include assessing changes in VTA activation and functional connectivity over time, as well as examining how neural changes relate to mood and motivation-related changes.
- Conditions
- Major Depressive Disorder (MDD)
- Being tested
- Active Biofeedback, Sham Biofeedback
- Keywords
- Brain imaging, Biofeedback, 7-Tesla MRI, Depression, Dopamine
- 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.
Active BiofeedbackBehavioural
The active biofeedback session will be done within the 7T MRI. It will include MOTIVATE and active rest trials. During each MOTIVATE trial, subjects will be instructed to generate a heightened state of motivation. Subjects will simultaneously view a progress bar on the screen during MOTIVATE trials that represents their VTA activity and they will be trained to try to increase the level of the bar by motivating themselves.
Sham BiofeedbackBehavioural
The sham biofeedback session resembles the active condition, however, the progress bar seen during the MOTIVATE trials will represent yoked sham values.
| Study group | Role | What they receive |
|---|---|---|
| Active Biofeedback | Experimental | The participants in the active group will receive repeated active biofeedback training sessions. Receives: Behavioral: Active Biofeedback |
| Sham Biofeedback | Sham comparator | The participants in the sham group will receive repeated sham biofeedback training sessions. Receives: Behavioral: Sham Biofeedback |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mood and Motivation Related Measures
A single composite metric will be derived by factor analysis of a battery of validated mood and motivation related instruments (e.g. PANAS-SF, POMS-SF, PHQ-9, MAP-SR), providing one expected latent mood and motivation factor. Modelling the instruments jointly avoids nominating any single scale as the outcome, and controls for multiple comparisons. Unit of measure: standardized latent factor score (z / SD units).
Measured: Pre to post biofeedback training, within a 6-week timeframe.
VTA Connectivity
Functional connectivity between the VTA seed and whole-brain (voxelwise), measured with 7-Tesla fMRI. Unit of measure: Fisher z-transformed correlation coefficient.
Measured: Pre to post biofeedback training, within a 4-week timeframe.
Secondary outcomes (2)
VTA Activation
Blood-oxygen-level-dependent (BOLD) signal in the bilateral ventral tegmental area (VTA) region of interest for MOTIVATE versus active rest trials, measured with task-based 7-Tesla fMRI. Unit of measure: percent BOLD signal change.
Measured: Pre to post biofeedback training, within a 4-week timeframe.
Association between change in VTA measures and change in the mood and motivation factor
The standardized VTA activation and connectivity measure will each be tested for an association with change in the mood and motivation factor. One coefficient is reported per VTA measure. Unit of measure: standardized regression coefficient (dimensionless, from -1 to 1).
Measured: Pre to post biofeedback training, within a 6-week timeframe.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2026
- Study startJun 2026 (estimated)
- Primary completionJun 2031 (estimated)
- Study completionJun 2033 (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 OxfordThe 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
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Wellcome Trust
- Responsible party
- Sponsor
- Investigators
- Laurel S Morris, Dr, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07694076
- Sponsor's protocol ID
- MS IDREC 879781
- Other IDs
- 226532/Z/22/Z
- Status last verified
- Jun 2026
- First submitted
- 4 Jun 2026
- Last updated
- 9 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided