Brain Signal Training to Enhance Affect Down-regulation

NCT ID: NCT06626789

Last Updated: 2026-02-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

164 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-04-23

Study Completion Date

2028-06-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Borderline Personality Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors
Clinical Research Organization (sub-contractor) responsible for interim analysis

Study Groups

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Intervention group

Real-time functional Magnetic Resonance Imaging (fMRI) neurofeedback from the Blood Oxygenation Level Dependent (BOLD) signal of the amygdala

Group Type EXPERIMENTAL

Amygdala neurofeedback

Intervention Type BIOLOGICAL

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.

Control group

Feedback that is less correlated with amygdala BOLD signal

Group Type EXPERIMENTAL

Sham neurofeedback

Intervention Type BEHAVIORAL

Recorded neurofeedback from a different participant + negative emotional picture viewing. Instruction to regulate feedback via down-regulation of one's emotional response.

Interventions

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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.

Intervention Type BIOLOGICAL

Sham neurofeedback

Recorded neurofeedback from a different participant + negative emotional picture viewing. Instruction to regulate feedback via down-regulation of one's emotional response.

Intervention Type BEHAVIORAL

Eligibility Criteria

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Inclusion Criteria

1. 18-65 years
2. Diagnosis of Borderline Personality Disorder
3. Insufficient response to ≥2 therapies.
4. 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
5. Ability of subject to understand character and individual consequences of clinical investigation
6. Written informed consent (must be available before enrollment in the clinical investigation)
7. For women of childbearing potential (WOCBP) adequate contraception.

Exclusion Criteria

1. Treatment with benzodiazepines within 7 days prior the initial screening
2. Current alcohol or substance dependence
3. Meeting the diagnostic criteria for a psychotic disorder or schizophrenia (life-time), as determined by clinical interview at initial screening
4. 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)
5. Significant visual impairment that might interfere with the performance of the behavioural tasks or fMRI tasks
6. Change of treatment (psychopharmacologic, psychological) 2 weeks prior to or during the study participation
7. Treatment with any neurofeedback three months prior to or during the study participation.
8. Unable or unwilling to comply with study procedures, including study prohibitions and restrictions
9. History of claustrophobia or inability to tolerate scanner environment
10. Fulfilling any of the MRI contraindications on the standard site radiography screening questionnaire (e.g. history of surgery involving metal implants)
11. Clinically relevant structural brain abnormality as determined by prior MRI scan
12. Planned medical treatment within the study period that might interfere with the study procedures
13. Participants deemed to be at significant risk of serious violence or suicide
14. BMI of 16.5 or lower
15. Participation in other clinical trials or observation period of competing trials, respectively
16. Previous participation in this trial
17. Pregnancy and lactation
18. Held in an institution by legal or official order
19. Legally incapacitated.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Medical Center Freiburg

OTHER

Sponsor Role collaborator

University of Giessen

OTHER

Sponsor Role collaborator

University Hospital Tuebingen

OTHER

Sponsor Role collaborator

Central Institute of Mental Health, Mannheim

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Christian Paret-Voigt, Dr.

Role: PRINCIPAL_INVESTIGATOR

ZI Mannheim

Locations

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University clinic Freiburg

Freiburg im Breisgau, , Germany

Site Status RECRUITING

University clinic Giessen

Giessen, , Germany

Site Status RECRUITING

University Clinic Halle (Saale)

Halle, , Germany

Site Status NOT_YET_RECRUITING

University Medical Center Hamburg-Eppendorf

Hamburg, , Germany

Site Status RECRUITING

Central Institute of Mental Health

Mannheim, , Germany

Site Status RECRUITING

University Clinic Tuebingen

Tübingen, , Germany

Site Status RECRUITING

Countries

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Germany

Central Contacts

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Christian Paret-Voigt, Dr.

Role: CONTACT

+4962117034462

Miroslava Hofmanová

Role: CONTACT

+4962117034463

Facility Contacts

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Simon Maier, Dr.

Role: primary

+49 (0) 761 65530

Christian Schoenholz, Dr.

Role: primary

+49 (0) 641 985 45702

Jana Weise

Role: primary

+49-345-557-3795

Gregor Leicht

Role: primary

+49-40-7410-59520

Christian Paret, Dr.

Role: primary

+49 621 1703 ext. 4462

Miroslava Jindrová

Role: backup

+49 621 1703 ext. 4463

Beatrix Barth, Dr.

Role: primary

+49 (0) 761 65530

References

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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.

Reference Type BACKGROUND
PMID: 31795041 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26833918 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25278851 (View on PubMed)

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. BMC Psychiatry. 2025 Jul 8;25(1):687. doi: 10.1186/s12888-025-07000-1.

Reference Type DERIVED
PMID: 40629288 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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BrainSTEADy

Identifier Type: -

Identifier Source: org_study_id

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