A Phase 1/2 interventional study of Amygdala neurofeedback and Sham neurofeedback in Borderline Personality Disorder, sponsored by Central Institute of Mental Health, Mannheim. Recruiting at 6 sites in Germany. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-08-17.
Sponsored by Central Institute of Mental Health, Mannheim · Phase 1/2, Interventional, and Treatment
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.
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.
278 studies on the registry are indexed under Borderline Personality Disorder; 70 are open to participants now.
This study's planned enrollment of 164 is above the median of 70 across 221 interventional studies indexed under Borderline Personality Disorder.
Browse Borderline Personality Disorder studies →Central Institute of Mental Health, Mannheim is the lead sponsor of 60 studies on the registry; 9 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Stage 1: 82 patients, stage 2: 82 patients Inclusion Criteria
Exclusion Criteria
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
TIA (transient ischaemic attack)
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Real-time functional Magnetic Resonance Imaging (fMRI) neurofeedback from the Blood Oxygenation Level Dependent (BOLD) signal of the amygdala
Biological: Amygdala neurofeedback
Feedback that is less correlated with amygdala BOLD signal
Behavioral: Sham 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.
Recorded neurofeedback from a different participant + negative emotional picture viewing. Instruction to regulate feedback via down-regulation of one's emotional response.
Affect Intensity, change from T0 to T1
Mean score of negative affect scale measured via experience sampling using ecological momentary assessment (EMA). Scale can take values from 1 to 7, high values mean higher affect intensity. EMA is conducted across 4 consecutive days, including a full weekend, when patients carry a smartphone that runs the EMA app. The app sends an auditory signal every hour, starting at 9 AM until 9 PM, to remind the patient to fill out the items.
Time frame: Completion of T0 EMA sampling within 12 days before first NF session. Start of T1 EMA sampling within 1 week after last NF session.
Affect Intensity, change from T0 to T2
Mean score of negative affect scale measured via experience sampling using ecological momentary assessment (EMA). Scale can take values from 1 to 7, high values mean higher affect intensity. EMA is conducted across 4 consecutive days, including a full weekend, when patients carry a smartphone that runs the EMA app. The app sends an auditory signal every hour, starting at 9 AM until 9 PM, to remind the patient to fill out the items.
Time frame: 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
Zanarini Rating Scale for BPD, interview version (ZAN-BPD) total score. Total score can take values 0-36 with higher values meaning higher symptom burden.
Time frame: 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.
BOLD-fMRI response in the amygdala to negative stimuli in the view-condition, during NF session 1, run 1, vs. last NF session, last run.
Time frame: Time Frame: T0 assessed at Baseline. T1 assessed at Post-Assessment immediately after treatment.
Amygdala self-regulation, change from T0 to T1.
BOLD-fMRI response in the amygdala to negative stimuli in the regulate-condition, during NF session 1, run 1, vs. last NF session, last run.
Time frame: 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
We measure health-related quality of life with the AQoL-6D (Centre for Health Economics, Monash University, 2016), a multi attribute utility instrument frequently used in health economic evaluations. We elicit quality adjusted life years (QALYs) from the AQoL-6D unweighted scorings by using established value sets. The derived QALYs range from 0.00 to 1.00, where 0.00 represents death and 1.00 a year in perfect health. We combine effects (QALYs) and costs of utilization between groups to receive incremental cost-effectiveness ratios (ICER). Thus, we are able to present costs per QALY for the neurofeedback intervention to inform stakeholders in health care about reimbursement decisions.
Time frame: T0 assessed before first nf session (within 1-3 weeks). T3 assessed 6 months after last NF session.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Pseudonymized and de-identified data will be uploaded to a data repository hosted by University of Heidelberg (heiDATA).
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Analytic code
Time frame: The data will be made available within 1 year after completion of data collection. Data will be available for at least 10 years.
Access criteria: IPD can be shared with researchers who are located in countries with a data protection level that is equivalent with the EU-GDPR. Researcher have to request access at the repository website.
Started Apr 2025 (actual). Primary completion is estimated for Dec 2027, 32 months after the start.
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Borderline Personality Disorder →
Central Institute of Mental Health, Mannheim