Rapid Entrainment and Signal-guided Neuromodulation for Behavioral Health

N/AActive Not RecruitingNCT07812987

Tactical Mind Research Coalition, Inc.240 enrolled

Overview

RESYNC-BH is a research study evaluating a personalized, non-drug brain-and-body treatment approach for adults with ongoing behavioral health symptoms such as depression, anxiety, trauma-related symptoms, sleep problems, attention difficulties, or substance-use concerns. Rather than assigning treatment solely according to psychiatric diagnosis, treatment approaches are selected based on symptoms, physiologic measures, and clinical presentation. Treatment may include noninvasive neuromodulation, sensory stimulation, regulated breathing, and AIP-informed integrative psychotherapy. The study will evaluate whether personalized treatment approaches produce rapid and sustained improvements in behavioral health symptoms and functioning, and whether treatment response is accompanied by measurable changes in neurophysiologic, autonomic, cognitive, inflammatory, and behavioral measures. The study hypothesis is that meaningful clinical improvement is associated with measurable changes across brain, body, cognitive, and behavioral signals, and that early changes in these measures may help characterize treatment response and its durability. The long-term goal is to develop more objective and personalized methods for monitoring behavioral health treatment response.

RESYNC-BH is a prospective, adaptive, transdiagnostic behavioral health study evaluating a personalized intervention platform (PRESET-Rx) and multimodal measures of treatment response. The study examines rapid within-session changes and longitudinal changes in neurophysiologic, autonomic, cognitive, inflammatory, and behavioral measures. Participants receive a personalized combination of noninvasive neuromodulation and AIP-informed integrative psychotherapy based on baseline symptoms, physiologic measures, and clinical presentation. Study interventions may include noninvasive brain or peripheral nerve stimulation, regulated breathing, sensory stimulation using light, sound or vibration, and related noninvasive techniques. Treatment assignment and adaptation occur according to prespecified study criteria. Multimodal assessments include EEG/qEEG, fNIRS, heart rate and heart rate variability, cognitive testing, standardized behavioral health measures, and inflammatory biomarkers. Selected sessions include simultaneous clinician-participant physiologic recording to evaluate therapeutic dyad dynamics. Optional data from compatible personal wearable devices may also be collected to characterize sleep, activity, and related physiologic patterns outside the clinic. The acute treatment phase consists of approximately six structured sessions over 4-6 weeks, followed by longitudinal assessments of treatment response and durability. Some participants may independently receive ketamine as part of routine clinical care. Ketamine is not a study intervention and is not assigned, initiated, scheduled, administered, or modified by the study. Ketamine exposure is recorded as a concomitant clinical treatment and may be considered in study analyses.

Interventions

AIP-Informed Integrative PsychotherapyBEHAVIORAL

A structured psychotherapy approach based on the Adaptive Information Processing (AIP) model, incorporating EMDR-informed techniques and other evidence-based psychotherapeutic strategies as clinically appropriate. The intervention is delivered as part of PRESET-Rx sessions to support processing and integration.

Transcutaneous Auricular Vagus Nerve StimulationDEVICE

Noninvasive transcutaneous auricular vagus nerve stimulation delivered through cutaneous ear electrodes according to prespecified protocol and safety parameters.

Regulated Breathing and Autonomic RegulationBEHAVIORAL

Structured breathing and related autonomic-regulation practices delivered according to prespecified protocol procedures.

Audiovisual EntrainmentDEVICE

Noninvasive patterned visual and auditory stimulation delivered according to prespecified protocol procedures as part of PRESET-Rx sessions.

Vibroacoustic StimulationDEVICE

Noninvasive mechanical vibration delivered through a vibroacoustic surface according to prespecified protocol procedures. This intervention may be used selectively based on protocol-defined clinical and safety considerations.

Breathwork-Based Auditory Driving Entropy Module (BADEM)BEHAVIORAL

A structured, time-limited breathwork and auditory stimulation procedure that may be used selectively according to prespecified protocol and safety criteria.

Transcranial Electrical StimulationDEVICE

Noninvasive low-intensity transcranial electrical stimulation delivered through scalp electrodes according to prespecified protocol and safety parameters.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age 18 to 70 years at the time of consent * Able to understand the study and provide signed informed consent * Willing and able to comply with study procedures and follow-up assessments for approximately 12 months * Presence of clinically significant behavioral-health symptoms and/or functional impairment in at least one of the following domains, as determined by clinical interview and standardized measures: * Depressive symptoms * Anxiety symptoms * Trauma- and stressor-related symptoms * Substance-related symptoms not requiring immediate detoxification * Attentional/impulsivity or executive-function symptoms * A formal DSM-5 diagnosis is not required if symptoms and impairment are clinically meaningful and appropriate for outpatient behavioral-health intervention * Medically stable, in the judgment of the investigator, for outpatient behavioral-health treatment and applicable noninvasive neuromodulation or multisensory entrainment * If taking psychotropic or other relevant medications, on a stable dose for at least 4 weeks before baseline, with no planned changes during the acute intervention phase except as clinically necessary * Sufficient proficiency in English or another IRB-approved language to understand study procedures and provide informed consent, with approved translated materials or interpreter support when available * If of reproductive potential, agrees to applicable pregnancy-prevention requirements during the acute intervention phase * Willing to follow study lifestyle and safety requirements, including restrictions on alcohol and substance use before study sessions and applicable post-session safety recommendations Exclusion Criteria: * History of seizure disorder or other condition that, in the investigator's judgment, would make exposure to stroboscopic or patterned light stimulation unsafe * Severe photosensitivity or light sensitivity that could be worsened by exposure to flashing or patterned light * Implanted electronic or other medical device that is incompatible with study neuromodulation procedures * Unstable or clinically significant cardiovascular, neurologic, or other medical condition that could make study participation unsafe * Unstable or high-risk psychiatric condition, including: * Recent suicide attempt or current imminent suicide risk * Active psychosis * Uncontrolled mania or other acute psychiatric instability requiring a higher level of care * Pregnant or breastfeeding at screening or during participation * Acute intoxication or inability/unwillingness to comply with study safety restrictions regarding alcohol or non-prescribed/recreational substance use before study sessions * Unstable or rapidly changing psychotropic medication regimen at baseline * Concurrent participation in another interventional trial targeting behavioral health or neuromodulation that, in the investigator's judgment, would confound study outcomes or create a safety concern * Any other medical, psychiatric, cognitive, or behavioral condition that, in the investigator's judgment, would prevent safe participation or meaningful completion of study procedures

Outcomes

Primary Outcomes

Change in RESYNC Index Composite Score

The RESYNC Index is a standardized, unitless multimodal composite score designed to summarize treatment-related change across prespecified clinical/behavioral, autonomic, neurophysiologic, cognitive, and biomarker measures. The outcome is change from baseline in RESYNC Index score during the acute treatment phase and longitudinal follow-up. The index is interpreted according to the prespecified scoring framework, with change in score representing the magnitude and direction of multimodal treatment response. Unit of Measure: Standardized unitless composite score

Time frame: Baseline through 12 months

Secondary Outcomes

Clinician-Participant Heart Rate Variability Synchrony

Physiologic synchrony between the participant and clinician is assessed using simultaneous heart rate and heart rate variability (HRV) recordings obtained during selected treatment sessions. The outcome is a unitless HRV synchrony coefficient representing the degree of physiologic coupling between clinician and participant; higher values indicate greater synchrony. Unit of Measure: Unitless HRV synchrony coefficient

Time frame: Selected treatment sessions during the 6-week acute intervention phase

Clinician-Participant EEG Synchrony

Neural synchrony between the participant and clinician is assessed using simultaneous EEG recordings obtained during selected treatment sessions. The outcome is a unitless EEG synchrony coefficient representing the degree of inter-brain coupling between clinician and participant; higher values indicate greater synchrony. Unit of Measure: Unitless EEG synchrony coefficient

Time frame: Selected treatment sessions during the 6-week acute intervention phase

Clinician-Participant Electrodermal Activity Coupling

Electrodermal coupling will be calculated from simultaneous participant and clinician electrodermal activity recordings during selected sessions using a prespecified time-series coupling metric. Unit of Measure: Unitless coupling coefficient

Time frame: Selected treatment sessions during the 6-week acute intervention phase

Correlation Between Clinician-Participant EEG Synchrony and Acute Change in RESYNC Index

This outcome assesses the association between clinician-participant EEG synchrony measured during the acute treatment phase and change from baseline in the RESYNC Index at the end of acute treatment. The reported outcome is a correlation coefficient ranging from -1 to +1, where values farther from 0 indicate a stronger association and the sign indicates the direction of the relationship. Unit of Measure: Correlation coefficient

Time frame: EEG synchrony assessed during prespecified dyadic sessions through Week 6; RESYNC Index assessed at baseline and Week 6.

Change in Patient Health Questionnaire-9 Score

Depressive symptom severity will be assessed using the Patient Health Questionnaire-9 (PHQ-9), a 9-item self-report measure. Total scores range from 0 to 27, with higher scores indicating greater depressive symptom severity. The outcome is change in PHQ-9 total score from baseline over the acute intervention phase and follow-up period. Unit of Measure: Points on the PHQ-9 scale

Time frame: Baseline; prior to treatment sessions during Weeks 1-6; and follow-up at 1, 3, 6, and 12 months

Change in Generalized Anxiety Disorder-7 Score

Anxiety symptom severity will be assessed using the Generalized Anxiety Disorder-7 (GAD-7), a 7-item self-report measure. Total scores range from 0 to 21, with higher scores indicating greater anxiety symptom severity. The outcome is change in GAD-7 total score from baseline over the acute intervention phase and follow-up period. Unit of Measure: Points on the GAD-7 scale

Time frame: Baseline; prior to treatment sessions during Weeks 1-6; and follow-up at 1, 3, 6, and 12 months

Change in PTSD Checklist for DSM-5 Score

Post-traumatic stress symptom severity will be assessed using the PTSD Checklist for DSM-5 (PCL-5), a 20-item self-report measure. Total scores range from 0 to 80, with higher scores indicating greater PTSD symptom severity. The outcome is change in PCL-5 total score from baseline over the acute intervention phase and follow-up period. Unit of Measure: Points on the PCL-5 scale

Time frame: Baseline; prior to treatment sessions during Weeks 1-6; and follow-up at 1, 3, 6, and 12 months

Change in Depression Anxiety Stress Scales-8 Score

Global psychological distress will be assessed using the Depression Anxiety Stress Scales-8 (DASS-8), an 8-item self-report measure assessing depression, anxiety, and stress symptoms. Higher total scores indicate greater overall psychological distress. The outcome is change in DASS-8 total score from baseline over the acute intervention phase and follow-up period. Unit of Measure: Points on the DASS-8 scale

Time frame: Baseline; prior to treatment sessions during Weeks 1-6; and follow-up at 1, 3, 6, and 12 months

Rapid Entrainment and Signal-guided Neuromodulation for Behavioral Health

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes