Neurofeedback for Bipolar Disorder (NEUROFEED-BD)

• ClinicalTrials.gov Identifier: NCT05802446
• Recruitment Status: Not yet recruiting
• First Posted: April 6, 2023
• Last Update Posted: April 6, 2023
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Tracking Information

• First Submitted Date: February 28, 2023
• First Posted Date: April 6, 2023
• Last Update Posted Date: April 6, 2023
• Estimated Study Start Date: April 2023
• Estimated Primary Completion Date: May 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 27, 2023)

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.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: March 27, 2023)

• Montgomery and Asberg Depression Rating Scale (MADRS) [ Time Frame: Baseline, 3 weeks, and 4, 8 weeks after the end of the training. ]
  Evaluation of depressive symptoms. Total score ranging from 0 to 60, with higher scores indicating a greater severity of symptoms.
• Young Mania Rating Scale (YMRS) [ Time Frame: Baseline, 3 weeks, and 4, 8 weeks after the end of the training. ]
  Evaluation of manic symptoms. Total score ranging from 0 to 60, with higher scores indicating a greater severity of symptoms.
• Bipolar Depression Rating Scale (BDRS) [ Time Frame: Baseline, 3 weeks, and 4, 8 weeks after the end of the training. ]
  Evaluation of bipolar depression. Total score ranging from 0 to 60, with higher scores indicating a greater severity of symptoms.
• State-Trait Anxiety Inventory (STAI A-B) [ Time Frame: Baseline, 3 weeks, and 4, 8 weeks after the end of the training. ]
  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.
• Multidimensional Assessment of Thymic States - MAThyS [ Time Frame: Baseline, 3 weeks, and 4, 8 weeks after the end of the training. ]
  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.
• Affective Intensity Measure - AIM [ Time Frame: Baseline, 3 weeks, and 4, 8 weeks after the end of the training. ]
  Evaluation of emotion reactivity. Total score ranging from 20 to 120, with higher scores indicating higher strength or intensity of people's emotional experiences.
• Affective Lability Scale - ALS [ Time Frame: Baseline, 3 weeks, and 4, 8 weeks after the end of the training. ]
  Evaluation of mood lability. Total score ranging from 0 to 162, with higher scores indicating greater affective lability.
• Cognitive Emotion Regulation Questionnaire - CERQ [ Time Frame: Baseline, 3 weeks, and 4, 8 weeks after the end of the training. ]
  Evaluation of emotion regulation abilities. Subscales scores ranging from 4 to 20, with higher subscale scores indicating greater use of a specific cognitive strategy.
• Quality of life scale - QOLS [ Time Frame: Baseline, 3 weeks, and 4, 8 weeks after the end of the training. . ]
  Quality of life assessment. Score ranging from 1 to 5, 5 indicating better quality of life
• Five Facets Mindfulness Questionnaire - FFMQ [ Time Frame: Baseline, 3 weeks and 4, 8 weeks after the end of the training. ]
  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
• Global functioning assessment - GAF scale [ Time Frame: Baseline, 3 weeks, and 4, 8 weeks after the end of the training. ]
  Evaluation of global functioning. Total score ranging from 0 to 100, higher scores indicating better global functioning.
• Questionnaire of Adherence to the technology [ Time Frame: Baseline, 3 weeks. ]
  Evaluation of the score of the acceptability of neurofeedback. Total score ranging from 6 to 42, higher scores indicating better acceptability of the technology.
• Self-efficacy scale [ Time Frame: Baseline, 3 weeks. ]
  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.
• The Ekman facial recognition test [ Time Frame: Baseline, 3 weeks. ]
  Emotion recognition evaluation. Cognitive task
• The affective bias task [ Time Frame: Baseline, 3 weeks. ]
  Evaluation of emotional bias. Cognitive task
• The Test battery for Attentional Performance (TAP) [ Time Frame: Baseline, 3 weeks. ]
  Evaluation of attention. Cognitive task
• The choice reaction task [ Time Frame: Baseline, 3 weeks. ]
  Evaluation of mindwandering, meta-awareness and ruminations. Cognitive task
• MRI T1-T2 weighted scan [ Time Frame: Baseline, 3 weeks ]
  Evaluation of grey and white matter (micro)structure. MRI measurement
• MRI diffusion weighted scan [ Time Frame: Baseline, 3 weeks ]
  Evaluation of grey and white matter (micro)structure. MRI measurement
• functional MRI resting-state scan [ Time Frame: Baseline, 3 weeks ]
  Evaluation of brain functional connectivity. MRI measurement

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Neurofeedback for Bipolar Disorder
• Official Title: Real-time fMRI Neurofeedback as Treatment for Inter-critical Mood Symptoms in Bipolar Disorder : a Randomized Controlled Multicentric Trial

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Bipolar Disorder

Intervention

Other: Real-time fMRI Neurofeedback

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 Arms

• Experimental: Active feedback
  Group receiving "real" neurofeedback (NFB) (activity of the emotional brain network)
  Intervention: Other: Real-time fMRI Neurofeedback
• Sham Comparator: Sham feedback
  Group receiving "sham" NFB (activity from brain regions not implicated in emotion processing) to control for a potential placebo effect.
  Intervention: Other: Real-time fMRI Neurofeedback

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: March 27, 2023): 64
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 2025
• Estimated Primary Completion Date: May 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Josselin HOUENOU, Professor (MD, PhD); (+33)1 49 81 30 51; josselin.houenou@aphp.fr

Contact: Pauline Favre, Associate researcher (PhD); (+33)1 69 08 24 81; pauline.favre@cea.fr

• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT05802446
• Other Study ID Numbers: APHP180597
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: DATAS ARE OWN BY ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS, PLEASE CONTACT SPONSOR FOR FURTHER INFORMATION

• Current Responsible Party: Assistance Publique - Hôpitaux de Paris
• Original Responsible Party: Same as current
• Current Study Sponsor: Assistance Publique - Hôpitaux de Paris
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Assistance Publique - Hôpitaux de Paris
• Verification Date: February 2023