Brain Signal Training to Enhance Affect Down-regulation

Официальное название

A Multi-center, Patient-blinded and Investigator-blinded, Randomized, Parallel-group, Superiority Study to Compare the Efficacy of Four Sessions of Amygdala fMRI-BOLD Neurofeedback With Yoked Sham-control Neurofeedback in the Treatment of Dysregulated Affect in Borderline Personality Disorder

Обзор

Individuals with Borderline Personality Disorder (BPD) experience intensive, instable negative emotions. Hyperactivity of the amygdala is assumed to drive exaggerated emotional responses in BPD. Neurofeedback is an endogenous neuromodulation method to address the imbalance of neural circuits. Downregulation of amygdala hyperactivation with neurofeedback may ameliorate dysregulated emotions in BPD. The BrainSTEADy trial is designed to determine whether amygdala-fMRI-BOLD neurofeedback has a specific effect on affect instability in BPD beyond nonspecific benefit.

Подробное описание

Borderline Personality Disorder (BPD) is characterized by self-mutilation, suicidality, and severe interpersonal disturbances. These symptoms reflect pervasive emotion regulation problems. On the neural level, BPD patients show an inflated amygdala response to emotional cues. In addition, they have reduced neural control of the amygdala. The amygdala controls emotional experience and behavior. Therefore, current psychobiological theories consider amygdala hyper-activity a causal mechanism for emotional overreaction in BPD.

Functional magnetic resonance imaging (fMRI) allows the recording of activation in subcortical brain regions, such as the amygdala, in real time. Live feedback from brain activation (e.g. via a thermometer with the temperature reflecting the degree of activation) allows one to learn the voluntary control of the brain. Dubbed "neurofeedback" (NF), the method can result in long-lasting changes in neural activation patterns. NF allows precise targeting of dysfunctional neuro-circuitries that relate to clinical symptoms.

The project proposed here investigates the clinical effectivity of fMRI-based amygdala-NF training in BPD. In total, 164 patients will participate in four training sessions provided by four study centers: Tuebingen, Freiburg, Giessen, and Mannheim. The training aims to reduce affective instability in everyday life, which is assessed primarily by ambulatory assessment before and after treatment. During NF sessions, patients receive feedback from the BOLD (Blood Oxygenation Level Dependent) signal recorded in the amygdala while they view pictures with negative emotional content. The amygdala responds to these pictures with an activation increase. The patient observes the amygdala responding, illustrated via increased temperature in a thermometer beside the picture. The task is to decrease temperature. The procedure should teach patients to master overreaction at an early stage of neural emotion processing.

To assess the effectivity of amygdala-NF, a control group receives non-veridical feedback from a different patient. The investigators expect a significant reduction in affective instability with amygdala-NF. In addition, the investigators expect a greater reduction in affective instability in the amygdala-NF group versus the control group.

The trial will go through two stages of recruitment. Stage 1 is reached after recruitment of 82 participants. An interim analysis will be conducted. Depending on the results of the interim analysis, the trial will enter stage 2, ie. recruitment of the full number of planned participants.

Results from this study enable assessment of clinical efficacy of amygdala-NF. In the future, NF could serve as a precise tool for person-centered treatment of affective instability symptoms in mental disorders with severe emotion regulation problems such as BPD.

Вмешательства

• Биопрепарат Amygdala neurofeedback
  Real-time fMRI neurofeedback from amygdala's blood oxygenation level dependent (BOLD) signal + negative emotional picture viewing. Instruction to regulate feedback via down-regulation of one's emotional response.
• Поведенческое Sham neurofeedback
  Recorded neurofeedback from a different participant + negative emotional picture viewing. Instruction to regulate feedback via down-regulation of one's emotional response.

Первичные конечные точки

• Affect Intensity, change from T0 to T1 [Срок оценки: Completion of T0 EMA sampling within 12 days before first NF session. Start of T1 EMA sampling within 1 week after last NF session.]

Вторичные конечные точки (5)

• Affect Intensity, change from T0 to T2 [Срок оценки: Completion of T0 EMA sampling within 12 days before first NF session. Start of T2 EMA sampling within 14-16 weeks after last NF session.]
• Borderline Symptom Severity, change from T0 to T1 and T0 to T2 [Срок оценки: T0 assessed before first NF session (within 1-3 weeks). T1 assessed after last NF session (within 2-4 weeks). T2 assessed within 14-16 weeks after last NF session.]
• Amygdala response, change from T0 to T1. [Срок оценки: Time Frame: T0 assessed at Baseline. T1 assessed at Post-Assessment immediately after treatment.]
• Amygdala self-regulation, change from T0 to T1. [Срок оценки: Time Frame: T0 assessed at Baseline. T1 assessed at Post-Assessment immediately after treatment.]
• Improvement in quality-adjusted life years (QALY), change from T0 to T3 [Срок оценки: T0 assessed before first nf session (within 1-3 weeks). T3 assessed 6 months after last NF session.]

Критерии участия

Stage 1: 82 patients, stage 2: 82 patients Inclusion Criteria

• 18-65 years
• Diagnosis of Borderline Personality Disorder
• Insufficient response to ≥2 therapies.
• Sufficient German language skills to give informed consent to the study, to understand questions posed by used instruments, and capable of completing the fMRI tasks
• Ability of subject to understand character and individual consequences of clinical investigation
• Written informed consent (must be available before enrollment in the clinical investigation)
• For women of childbearing potential (WOCBP) adequate contraception.

Критерии исключения

• Treatment with benzodiazepines within 7 days prior the initial screening
• Current alcohol or substance dependence
• Meeting the diagnostic criteria for a psychotic disorder or schizophrenia (life-time), as determined by clinical interview at initial screening
• Current or history of significant neurological condition (such as stroke, traumatic brain injury, space occupying lesions, multiple sclerosis, Parkinson's disease, vascular dementia, transient ischemic attack)
• Significant visual impairment that might interfere with the performance of the behavioural tasks or fMRI tasks
• Change of treatment (psychopharmacologic, psychological) 2 weeks prior to or during the study participation
• Treatment with any neurofeedback three months prior to or during the study participation.
• Unable or unwilling to comply with study procedures, including study prohibitions and restrictions
• History of claustrophobia or inability to tolerate scanner environment
• Fulfilling any of the MRI contraindications on the standard site radiography screening questionnaire (e.g. history of surgery involving metal implants)
• Clinically relevant structural brain abnormality as determined by prior MRI scan
• Planned medical treatment within the study period that might interfere with the study procedures
• Participants deemed to be at significant risk of serious violence or suicide
• BMI of 16.5 or lower
• Participation in other clinical trials or observation period of competing trials, respectively
• Previous participation in this trial
• Pregnancy and lactation
• Held in an institution by legal or official order
• Legally incapacitated.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Германия · 6 центров

• University clinic Freiburg — Freiburg im Breisgau
• University clinic Giessen — Giessen
• University Clinic Halle (Saale) — Halle
• University Medical Center Hamburg-Eppendorf — Hamburg
• Central Institute of Mental Health — Mannheim
• University Clinic Tuebingen — Tübingen

Публикации

• Zaehringer J, Ende G, Santangelo P, Kleindienst N, Ruf M, Bertsch K, Bohus M, Schmahl C, Paret C. Improved emotion regulation after neurofeedback: A single-arm trial in patients with borderline personality disorder. Neuroimage Clin. 2019;24:102032. doi: 10.1016/j.nicl.2019.102032. Epub 2019 Oct 16. PMID 31795041
• Paret C, Kluetsch R, Zaehringer J, Ruf M, Demirakca T, Bohus M, Ende G, Schmahl C. Alterations of amygdala-prefrontal connectivity with real-time fMRI neurofeedback in BPD patients. Soc Cogn Affect Neurosci. 2016 Jun;11(6):952-60. doi: 10.1093/scan/nsw016. Epub 2016 Feb 1. PMID 26833918
• Paret C, Kluetsch R, Ruf M, Demirakca T, Hoesterey S, Ende G, Schmahl C. Down-regulation of amygdala activation with real-time fMRI neurofeedback in a healthy female sample. Front Behav Neurosci. 2014 Sep 18;8:299. doi: 10.3389/fnbeh.2014.00299. eCollection 2014. PMID 25278851
• Paret C, Jindrova M, Kleindienst N, Eck J, Breman H, Luhrs M, Barth B, Ethofer T, Fallgatter AJ, Goebel R, Hoell A, Lockhofen D, Reinhold AS, Maier S, Matthies S, Mulert C, Schonholz C, van Elst LT, Schmahl C. A randomised controlled trial of amygdala fMRI-neurofeedback versus sham-feedback in borderline-personality disorder - systematic literature review and introduction to the BrainSTEADy trial. PMID 40629288

Идентификаторы

NCT: NCT06626789 · BrainSTEADy

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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