Rapid Entrainment and Signal-guided Neuromodulation for Behavioral Health

NCT07812987 | Active Not Recruiting DMC FDA Device

• 2 other identifiers: 26-01TMRC 26-01
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Anxiety; PTSD; ADHD; Depression Disorders; Post-traumatic Stress; Substance Use; Executive Function; Sleep Disturbance

Keywords

neuroplasticity; audiovisual entrainment; biomarkers; inflammation; cognition; neuromodulation; multisensory entrainment; transcranial electrical stimulation; auricular vagus nerve stimulation; EMDR; Adaptive Information Processing; Predictive processing; Heart rate variability; EEG; fNIRS; Dyadic synchrony; therapeutic alliance; digital phenotyping; autonomic regulation; precision mental health; adaptive intervention; SMART design

Outcome Measures

Primary Outcomes (1)

• 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

  Baseline through 12 months

Secondary Outcomes (8)

• Clinician-Participant Heart Rate Variability Synchrony

  Selected treatment sessions during the 6-week acute intervention phase

• Clinician-Participant EEG Synchrony

  Selected treatment sessions during the 6-week acute intervention phase

• Clinician-Participant Electrodermal Activity Coupling

  Selected treatment sessions during the 6-week acute intervention phase

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

  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

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

Other Outcomes (3)

• Within-Session Change in EEG Spectral Power

  Immediately before and immediately after each of the 6 acute treatment sessions, over approximately 6 weeks

• Within-Session Change in Heart Rate Variability

  Immediately before and immediately after each of the 6 acute treatment sessions, once per week over approximately 6 weeks

• Within-Session Change in Electrodermal Activity

  Immediately before and immediately after each of the 6 (weekly) acute treatment sessions, over approximately 6 weeks

Study Arms (4)

Stack A - Autonomic Regulation + AIP-Informed Integrative Psychotherapy

EXPERIMENTAL

Participants assigned to Stack A receive a PRESET-Rx intervention emphasizing autonomic regulation, combined with AIP-informed integrative psychotherapy. The intervention may include noninvasive peripheral neuromodulation, regulated breathing, and related autonomic-regulation techniques, with treatment delivered according to prespecified protocol criteria. Physiologic and neurophysiologic measures are collected during study sessions.

Behavioral: AIP-Informed Integrative Psychotherapy; Device: Transcutaneous Auricular Vagus Nerve Stimulation; Behavioral: Regulated Breathing and Autonomic Regulation; Behavioral: Breathwork-Based Auditory Driving Entropy Module (BADEM)

Stack B - Multisensory Entrainment + AIP-Informed Integrative Psychotherapy

EXPERIMENTAL

Participants assigned to Stack B receive a PRESET-Rx intervention emphasizing multisensory state modulation, combined with AIP-informed integrative psychotherapy. The intervention may include noninvasive visual, auditory, and vibroacoustic stimulation, delivered according to prespecified protocol criteria. Physiologic and neurophysiologic measures are collected during study sessions.

Behavioral: AIP-Informed Integrative Psychotherapy; Device: Audiovisual Entrainment; Device: Vibroacoustic Stimulation; Behavioral: Breathwork-Based Auditory Driving Entropy Module (BADEM)

Stack C - Transcranial Electrical Stimulation + AIP-Informed Integrative Psychotherapy

EXPERIMENTAL

Participants assigned to Stack C receive a PRESET-Rx intervention emphasizing noninvasive cortical neuromodulation, combined with AIP-informed integrative psychotherapy. The intervention may include low-intensity transcranial electrical stimulation, delivered according to prespecified protocol criteria. Physiologic and neurophysiologic measures are collected during study sessions.

Behavioral: AIP-Informed Integrative Psychotherapy; Behavioral: Breathwork-Based Auditory Driving Entropy Module (BADEM); Device: Transcranial Electrical Stimulation

Stack D - AIP-Informed Integrative Psychotherapy

ACTIVE COMPARATOR

Participants assigned to Stack D receive AIP-informed integrative psychotherapy without active neuromodulation or multisensory stimulation. Study assessments and physiologic/neurophysiologic measurements are performed according to the same study procedures used across intervention arms. Stack D serves as the active psychotherapy comparator.

Behavioral: AIP-Informed Integrative Psychotherapy

Interventions

AIP-Informed Integrative Psychotherapy BEHAVIORAL

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.

Also known as: EMDR, Adaptive Information Processing-informed psychotherapy

Stack A - Autonomic Regulation + AIP-Informed Integrative Psychotherapy; Stack B - Multisensory Entrainment + AIP-Informed Integrative Psychotherapy; Stack C - Transcranial Electrical Stimulation + AIP-Informed Integrative Psychotherapy; Stack D - AIP-Informed Integrative Psychotherapy

Audiovisual Entrainment DEVICE

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

Also known as: AVE, patterned light and auditory entrainment

Stack B - Multisensory Entrainment + AIP-Informed Integrative Psychotherapy

Transcutaneous Auricular Vagus Nerve Stimulation DEVICE

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

Also known as: TaVNS

Stack A - Autonomic Regulation + AIP-Informed Integrative Psychotherapy

Vibroacoustic Stimulation DEVICE

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.

Also known as: Vibroacoustic entrainment, tactile acoustic stimulation

Stack B - Multisensory Entrainment + AIP-Informed Integrative Psychotherapy

Regulated Breathing and Autonomic Regulation BEHAVIORAL

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

Stack A - Autonomic Regulation + AIP-Informed Integrative Psychotherapy

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.

Stack A - Autonomic Regulation + AIP-Informed Integrative Psychotherapy; Stack B - Multisensory Entrainment + AIP-Informed Integrative Psychotherapy; Stack C - Transcranial Electrical Stimulation + AIP-Informed Integrative Psychotherapy

Transcranial Electrical Stimulation DEVICE

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

Also known as: tES, transcranial electrical neuromodulation

Stack C - Transcranial Electrical Stimulation + AIP-Informed Integrative Psychotherapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Tactical Mind Research Coalition, Inc.: lead

Study Sites (1)

Tactical Mind Research Coalition

Tampa, Florida, 33618, United States

Location

Related Publications (4)

• Chamberlin DE. The Predictive Processing Model of EMDR. Front Psychol. 2019 Oct 4;10:2267. doi: 10.3389/fpsyg.2019.02267. eCollection 2019.

  PMID: 31636594 BACKGROUND

• FAA Mental Health ARC. (2024). MENTAL HEALTH ARC FINAL REPORT. Federal Aviation Administration

  BACKGROUND

• 11. VA Office of Mental Health and Suicide Prevention. (2024). NATIONAL VETERAN SUICIDE PREVENTION ANNUAL REPORT.

  BACKGROUND

• Carhart-Harris RL, Friston KJ. REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics. Pharmacol Rev. 2019 Jul;71(3):316-344. doi: 10.1124/pr.118.017160.

  PMID: 31221820 BACKGROUND

MeSH Terms

Conditions

Anxiety Disorders; Stress Disorders, Post-Traumatic; Attention Deficit Disorder with Hyperactivity; Substance-Related Disorders; Parasomnias; Inflammation

Interventions

Eye Movement Desensitization Reprocessing; Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

Mental Disorders; Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Chemically-Induced Disorders; Sleep Wake Disorders; Nervous System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Desensitization, Psychologic; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities; Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Electroshock; Psychological Techniques

Study Officials

• Brian Pinkston, MD, MPH

  Tactical Mind Research Coalition

  PRINCIPAL INVESTIGATOR

• Cheryl Lowry, MD, MPH

  Tactical Mind Research Coalition

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Participants and treating investigators are not masked because the intervention modalities are readily distinguishable. To reduce analytic bias, designated data analysts may be masked to intervention stack assignment and session-phase labels during initial feature selection and model development until prespecified analyses are locked.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: RESYNC-BH uses a Sequential Multiple Assignment Randomized Trial (SMART) design evaluating four predefined intervention approaches. Participants are initially randomized among intervention options determined to be appropriate based on prespecified clinical and physiologic criteria. Treatment response and safety are assessed during the acute intervention phase. At prespecified decision points, treatment may be continued or adapted according to protocol-defined response and safety criteria. Clinical safety considerations supersede randomization.

Study Record Dates

• First Submitted: December 11, 2025
• First Posted: September 10, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: September 16, 2026

Record last verified: 2026-09

Locations

US (1)