Bipolar DisorderNEUROFEED-BDNCT05802446
Neurofeedback for Bipolar Disorder
A study testing Real-time fMRI Neurofeedback in people with Bipolar Disorder, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Bipolar Disorder (BD) is a severe mood disorder affecting between 1% and 3% of the general population. It is characterized by the succession of depressive and manic episodes, with periods of stabilization during which patients may present "residual" depressive or anxious symptoms, which are characterized by sadness… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Bipolar Disorder
- What is being tested?
- Real-time fMRI Neurofeedback
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- 1 siteFrance
- Study dates
- 22 May 2024to Sep 2026
- 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
- Patients diagnosed with bipolar disorder I or II (DSM-5 criteria);
- Aged between ≥ 18 and ≤ 65;
- Absence of major mood episode for at least 3 months before inclusion (MADRS scores < 12; YMRS score < 10);
- Presence of residual depressive symptoms, as assessed by the MADRS (score > 5);
- Stabilized dose of mood stabilizer medication for at least 3 months before inclusion.
- Written consent
- Affiliation to a social security system
- Effective contraception for women of childbearing age
Who cannot join
- Severe physical disorders that may be life-threatening;
- Major psychiatric (Axis 1) comorbidities except for anxiety disorders;
- Any current substance abuse except for tobacco or cannabis. Substance abuse will be defined by the DSM V criteria;
- Exclusion criteria applicable to MRI Panic disorder, claustrophobia, epilepsy Pace maker or neuronal stimulator, intraocular or intracerebral metallic foreign body, cochlear implant, cardiac valve or metallic surgical arterial material, non removable removable magnetizable metallic material
- Somatic disorder that may affect cognitive abilities and brain structures (e.g., HIV infection, MS, lupus, Parkinson's disease, epilepsy, dementia...);
- Ongoing non-pharmacological treatment: structured psychotherapeutic interventions (Cognitive Behavioral Therapy - CBT, Interpersonal and Social Rhythm Therapy - IPSRT) as well as brain stimulation techniques (Electroconvulsive Therapy - ECT, Transcranial Magnetic Stimulation - TMS, Deep Brain Stimulation - DBS);
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- Subject included in clinical and / or therapeutic experimentation in progress.
- Patients under legal protection
- Prisoners
- Pregnancy
- Breastfeeding
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Albert Chenevier
Créteil, val-de-marne, 94000
About this study
Official title: Real-time fMRI Neurofeedback as Treatment for Inter-critical Mood Symptoms in Bipolar Disorder : a Randomized Controlled Multicentric Trial
Bipolar Disorder (BD) is a severe mood disorder affecting between 1% and 3% of the general population. It is characterized by the succession of depressive and manic episodes, with periods of stabilization during which patients may present "residual" depressive or anxious symptoms, which are characterized by sadness and emotional hyper-reactivity. Although subthreshold, these residual symptoms are very disabling for their daily lives and are associated with the risk of recurrence and poor global functioning. The effect of pharmacological and psychotherapeutic treatments is demonstrated in the management of acute episodes but remains insufficient on residual symptoms. Therefore, there are so far few therapeutic options to target the inter-episode residual symptoms in BD. One novel approach is the real-time functional magnetic resonance imaging (fMRI) neurofeedback (NFB), which has already been shown to be an efficient method for self-regulating brain function, behavior and treating depression.
Hypothesis/Objective :
Read more
This study aims at assessing the efficacy of 3-weeks neurofeedback training with real-time fMRI on the treatment of residual mood symptoms in patients with BD. The investigators will specifically target depressive symptoms by training the patients to regulate the emotional network hemodynamic response to emotional stimuli.
Method :
The investigators will include 64 stabilized patients with BD. The investigators will recruit them in three French expert centers for BD and will randomly assign them to the experimental group, receiving feedback from the emotional brain network hemodynamic activity, or to the control group, receiving the signal from control brain areas not involved in emotion processing. Both groups will be trained to regulate their brain activity while they are presented with negatively valenced emotional pictures, based on the neurofeedback shown immediately after the trial. They will continue their usual treatment (as prescribed) throughout the duration of the study. Clinical scales and cognitive tests will enable us to evaluate the symptomatic, emotional, and cognitive changes after NFB training. The investigators will also measure resting-state functional connectivity and brain morphology before and after NFB to assess brain plasticity and to explore the neural mechanisms associated with successful regulation.
- Conditions
- Bipolar Disorder
- Being tested
- Real-time fMRI Neurofeedback
- Keywords
- Bipolar disorder, Neurofeedback, fMRI, Residual symptoms, Emotion, Cognitive training
- Medical subject headings
- Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Real-time fMRI NeurofeedbackOther
Neurofeedback with real-time fMRI is a recent technique that allows to record the BOLD signal from a particular brain region and to display it back in real-time to the participant. With this feedback on brain activity, subjects can learn to control the activity of selected brain areas. Trial after trial, participants develop their individual strategies to voluntarily regulate the signal. The main objective of the neurofeedback training is that the participant develops an enhanced ability to exert control over activity in the target area(s) even without feedback. By manipulating targeted brain circuits, this training can induce modifications in particular behaviors and promote selective plasticity within the corresponding brain networks.
| Study group | Role | What they receive |
|---|---|---|
| Active feedback | Experimental | Group receiving "real" neurofeedback (NFB) (activity of the emotional brain network) Receives: Other: Real-time fMRI Neurofeedback |
| Sham feedback | Sham comparator | Group receiving "sham" NFB (activity from brain regions not implicated in emotion processing) to control for a potential placebo effect. Receives: Other: Real-time fMRI Neurofeedback |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Evaluation of depressive symptoms. Total score ranging from 0 to 60, with higher scores indicating a greater severity of symptoms.
Measured: Baseline, 3 weeks.
Secondary outcomes (20)
Montgomery and Asberg Depression Rating Scale (MADRS)
Evaluation of depressive symptoms. Total score ranging from 0 to 60, with higher scores indicating a greater severity of symptoms.
Measured: Baseline, 3 weeks, and 4, 8 weeks after the end of the training.
Young Mania Rating Scale (YMRS)
Evaluation of manic symptoms. Total score ranging from 0 to 60, with higher scores indicating a greater severity of symptoms.
Measured: Baseline, 3 weeks, and 4, 8 weeks after the end of the training.
Bipolar Depression Rating Scale (BDRS)
Evaluation of bipolar depression. Total score ranging from 0 to 60, with higher scores indicating a greater severity of symptoms.
Measured: Baseline, 3 weeks, and 4, 8 weeks after the end of the training.
State-Trait Anxiety Inventory (STAI A-B)
Evaluation of trait and state anxiety. Total score ranging from 20 to 80 for both subscales, with higher scores indicating a greater severity of symptoms.
Measured: Baseline, 3 weeks, and 4, 8 weeks after the end of the training.
Multidimensional Assessment of Thymic States - MAThyS
Evaluation of thymic state. Total score ranging from 0 to 200, lower scores indicate general inhibition, and higher scores indicate general excitation. A more descriptive approach can be done by analysing the sub-score.
Measured: Baseline, 3 weeks, and 4, 8 weeks after the end of the training.
Affective Intensity Measure - AIM
Evaluation of emotion reactivity. Total score ranging from 20 to 120, with higher scores indicating higher strength or intensity of people's emotional experiences.
Measured: Baseline, 3 weeks, and 4, 8 weeks after the end of the training.
Affective Lability Scale - ALS
Evaluation of mood lability. Total score ranging from 0 to 162, with higher scores indicating greater affective lability.
Measured: Baseline, 3 weeks, and 4, 8 weeks after the end of the training.
Cognitive Emotion Regulation Questionnaire - CERQ
Evaluation of emotion regulation abilities. Subscales scores ranging from 4 to 20, with higher subscale scores indicating greater use of a specific cognitive strategy.
Measured: Baseline, 3 weeks, and 4, 8 weeks after the end of the training.
Quality of life scale - QOLS
Quality of life assessment. Score ranging from 1 to 5, 5 indicating better quality of life
Measured: Baseline, 3 weeks, and 4, 8 weeks after the end of the training. .
Five Facets Mindfulness Questionnaire - FFMQ
Evaluation of trait mindfulness. Total score ranging from 39 to 195, higher scores are indicative of someone who is more mindful in their everyday life
Measured: Baseline, 3 weeks and 4, 8 weeks after the end of the training.
Global functioning assessment - GAF scale
Evaluation of global functioning. Total score ranging from 0 to 100, higher scores indicating better global functioning.
Measured: Baseline, 3 weeks, and 4, 8 weeks after the end of the training.
Questionnaire of Adherence to the technology
Evaluation of the score of the acceptability of neurofeedback. Total score ranging from 6 to 42, higher scores indicating better acceptability of the technology.
Measured: Baseline, 3 weeks.
Self-efficacy scale
Evaluation of personal efficiency. Total score ranging from 21 to 105, higher scores indicating stronger belief that one's actions are responsible for successful outcomes.
Measured: Baseline, 3 weeks.
The Ekman facial recognition test
Emotion recognition evaluation. Cognitive task
Measured: Baseline, 3 weeks.
The affective bias task
Evaluation of emotional bias. Cognitive task
Measured: Baseline, 3 weeks.
The Test battery for Attentional Performance (TAP)
Evaluation of attention. Cognitive task
Measured: Baseline, 3 weeks.
The choice reaction task
Evaluation of mindwandering, meta-awareness and ruminations. Cognitive task
Measured: Baseline, 3 weeks.
MRI T1-T2 weighted scan
Evaluation of grey and white matter (micro)structure. MRI measurement
Measured: Baseline, 3 weeks
MRI diffusion weighted scan
Evaluation of grey and white matter (micro)structure. MRI measurement
Measured: Baseline, 3 weeks
functional MRI resting-state scan
Evaluation of brain functional connectivity. MRI measurement
Measured: Baseline, 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2023
- Study start22 May 2024
- Primary completionSep 2026 (estimated)
- Study completionSep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bipolar DisorderStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- 64 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05802446
- Sponsor's protocol ID
- APHP180597
- Acronym
- NEUROFEED-BD
- Status last verified
- Jul 2025
- First submitted
- 28 Feb 2023
- Last updated
- 15 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: DATAS ARE OWN BY ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS, PLEASE CONTACT SPONSOR FOR FURTHER INFORMATION
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Real-time fMRI Neurofeedback as Treatment for Inter-critical Mood Symptoms in Bipolar Disorder : a Randomized Controlled Multicentric Trial
- ClinicalTrials.gov ID
- NCT05802446
- Acronym / sponsor ID
- NEUROFEED-BD / APHP180597
- Conditions
- Bipolar Disorder
- Keywords
- Bipolar disorder, Neurofeedback, fMRI, Residual symptoms, Emotion, Cognitive training
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 64 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 22 May 2024 (actual)
- Primary completion
- Sep 2026 (estimated)
- Study completion
- Sep 2026 (estimated)
- First posted
- 6 Apr 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.
Bipolar Disorder (BD) is a severe mood disorder affecting between 1% and 3% of the general population. It is characterized by the succession of depressive and manic episodes, with periods of stabilization during which patients may present "residual" depressive or anxious symptoms, which are characterized by sadness and emotional hyper-reactivity. Although subthreshold, these residual symptoms are very disabling for their daily lives and are associated with the risk of recurrence and poor global functioning. The effect of pharmacological and psychotherapeutic treatments is demonstrated in the management of acute episodes but remains insufficient on residual symptoms. Therefore, there are so far few therapeutic options to target the inter-episode residual symptoms in BD. One novel approach is the real-time functional magnetic resonance imaging (fMRI) neurofeedback (NFB), which has already been shown to be an efficient method for self-regulating brain function, behavior and treating depression.
Hypothesis/Objective :
This study aims at assessing the efficacy of 3-weeks neurofeedback training with real-time fMRI on the treatment of residual mood symptoms in patients with BD. The investigators will specifically target depressive symptoms by training the patients to regulate the emotional network hemodynamic response to emotional stimuli.
Method :
The investigators will include 64 stabilized patients with BD. The investigators will recruit them in three French expert centers for BD and will randomly assign them to the experimental group, receiving feedback from the emotional brain network hemodynamic activity, or to the control group, receiving the signal from control brain areas not involved in emotion processing. Both groups will be trained to regulate their brain activity while they are presented with negatively valenced emotional pictures, based on the neurofeedback shown immediately after the trial. They will continue their usual treatment (as prescribed) throughout the duration of the study. Clinical scales and cognitive tests will enable us to evaluate the symptomatic, emotional, and cognitive changes after NFB training. The investigators will also measure resting-state functional connectivity and brain morphology before and after NFB to assess brain plasticity and to explore the neural mechanisms associated with successful regulation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active feedback | Experimental | Other: Real-time fMRI NeurofeedbackGroup receiving "real" neurofeedback (NFB) (activity of the emotional brain network) |
| Sham feedback | Sham comparator | Other: Real-time fMRI NeurofeedbackGroup receiving "sham" NFB (activity from brain regions not implicated in emotion processing) to control for a potential placebo effect. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients diagnosed with bipolar disorder I or II (DSM-5 criteria);
- Aged between ≥ 18 and ≤ 65;
- Absence of major mood episode for at least 3 months before inclusion (MADRS scores < 12; YMRS score < 10);
- Presence of residual depressive symptoms, as assessed by the MADRS (score > 5);
- Stabilized dose of mood stabilizer medication for at least 3 months before inclusion.
Key exclusion criteria (11 listed)
- Severe physical disorders that may be life-threatening;
- Major psychiatric (Axis 1) comorbidities except for anxiety disorders;
- Any current substance abuse except for tobacco or cannabis. Substance abuse will be defined by the DSM V criteria;
- Exclusion criteria applicable to MRI Panic disorder, claustrophobia, epilepsy Pace maker or neuronal stimulator, intraocular or intracerebral metallic foreign body, cochlear implant, cardiac valve or metallic surgical arterial material, non removable removable magnetizable metallic material
- Somatic disorder that may affect cognitive abilities and brain structures (e.g., HIV infection, MS, lupus, Parkinson's disease, epilepsy, dementia...);
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 |
|---|---|---|
| Real-time fMRI NeurofeedbackNeurofeedback with real-time fMRI is a recent technique that allows to record the BOLD signal from a particular brain region and to display it back in real-time to the participant. With this feedback on brain activity, subjects can learn to control the activity of selected brain areas. Trial after trial, participants develop their individual strategies to voluntarily regulate the signal. The main objective of the neurofeedback training is that the participant develops an enhanced ability to exert control over activity in the target area(s) even without feedback. By manipulating targeted brain circuits, this training can induce modifications in particular behaviors and promote selective plasticity within the corresponding brain networks. | Other | Active feedback, Sham feedback |
Primary outcome
Changes in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Time frame: Baseline, 3 weeks.
Evaluation of depressive symptoms. Total score ranging from 0 to 60, with higher scores indicating a greater severity of symptoms.
20 secondary outcomes
Montgomery and Asberg Depression Rating Scale (MADRS)
Time frame: Baseline, 3 weeks, and 4, 8 weeks after the end of the training.
Young Mania Rating Scale (YMRS)
Time frame: Baseline, 3 weeks, and 4, 8 weeks after the end of the training.
Bipolar Depression Rating Scale (BDRS)
Time frame: Baseline, 3 weeks, and 4, 8 weeks after the end of the training.
State-Trait Anxiety Inventory (STAI A-B)
Time frame: Baseline, 3 weeks, and 4, 8 weeks after the end of the training.
Multidimensional Assessment of Thymic States - MAThyS
Time frame: Baseline, 3 weeks, and 4, 8 weeks after the end of the training.
Affective Intensity Measure - AIM
Time frame: Baseline, 3 weeks, and 4, 8 weeks after the end of the training.
Affective Lability Scale - ALS
Time frame: Baseline, 3 weeks, and 4, 8 weeks after the end of the training.
Cognitive Emotion Regulation Questionnaire - CERQ
Time frame: Baseline, 3 weeks, and 4, 8 weeks after the end of the training.
Quality of life scale - QOLS
Time frame: Baseline, 3 weeks, and 4, 8 weeks after the end of the training. .
Five Facets Mindfulness Questionnaire - FFMQ
Time frame: Baseline, 3 weeks and 4, 8 weeks after the end of the training.
Global functioning assessment - GAF scale
Time frame: Baseline, 3 weeks, and 4, 8 weeks after the end of the training.
Questionnaire of Adherence to the technology
Time frame: Baseline, 3 weeks.
Self-efficacy scale
Time frame: Baseline, 3 weeks.
The Ekman facial recognition test
Time frame: Baseline, 3 weeks.
The affective bias task
Time frame: Baseline, 3 weeks.
The Test battery for Attentional Performance (TAP)
Time frame: Baseline, 3 weeks.
The choice reaction task
Time frame: Baseline, 3 weeks.
MRI T1-T2 weighted scan
Time frame: Baseline, 3 weeks
MRI diffusion weighted scan
Time frame: Baseline, 3 weeks
functional MRI resting-state scan
Time frame: Baseline, 3 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 15 Jul 2025.
- Individual participant dataSharing planned: No. DATAS ARE OWN BY ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS, PLEASE CONTACT SPONSOR FOR FURTHER INFORMATION
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Real-time fMRI Neurofeedback in people with Bipolar Disorder, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 11 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 15 Jul 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 France. 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 Josselin HOUENOU, Professor (MD, PhD) ((+33)1 49 81 30 51, josselin.houenou@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score (time frame: Baseline, 3 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 15 Jul 2025.