Neurofeedback for Bipolar Disorder

NCT05802446 | Recruiting

• 1 other identifier: APHP180597
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Bipolar Disorder

Keywords

Bipolar disorder; Neurofeedback; fMRI; Residual symptoms; Emotion; Cognitive training

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline, 3 weeks.

Secondary Outcomes (20)

• Montgomery and Asberg Depression Rating Scale (MADRS)

  Baseline, 3 weeks, and 4, 8 weeks after the end of the training.

• Young Mania Rating Scale (YMRS)

  Baseline, 3 weeks, and 4, 8 weeks after the end of the training.

• Bipolar Depression Rating Scale (BDRS)

  Baseline, 3 weeks, and 4, 8 weeks after the end of the training.

• State-Trait Anxiety Inventory (STAI A-B)

  Baseline, 3 weeks, and 4, 8 weeks after the end of the training.

• Multidimensional Assessment of Thymic States - MAThyS

  Baseline, 3 weeks, and 4, 8 weeks after the end of the training.

Study Arms (2)

Active feedback

EXPERIMENTAL

Group receiving "real" neurofeedback (NFB) (activity of the emotional brain network)

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.

Other: Real-time fMRI Neurofeedback

Interventions

Real-time fMRI Neurofeedback OTHER

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.

Active feedback; Sham feedback

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients diagnosed with bipolar disorder I or II (DSM-5 criteria);
• Aged between ≥ 18 and ≤ 65;
• Presence of residual depressive symptoms, as assessed by the MADRS (score \> 5);
• Written consent
• Affiliation to a social security system
• Effective contraception for women of childbearing age

You may not qualify if:

• 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;
• 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);
• Subject included in clinical and / or therapeutic experimentation in progress.
• Patients under legal protection
• Prisoners
• Pregnancy
• Breastfeeding

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Albert Chenevier

Créteil, val-de-marne, 94000, France

RECRUITING

MeSH Terms

Conditions

Bipolar Disorder

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Central Study Contacts

Josselin HOUENOU, Professor (MD, PhD)

CONTACT

(+33)1 49 81 30 51; josselin.houenou@aphp.fr

Pauline Favre, Associate researcher (PhD)

CONTACT

(+33)1 69 08 24 81; pauline.favre@cea.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2023
• First Posted: April 6, 2023
• Study Start: May 22, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: July 15, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)