Regulated Stimulation for Optimized Network Activity and Therapeutic Equilibrium (RESONATE)

The objective of this study is to evaluate the safety, tolerability, and preliminary efficacy of the Motif eXternally powered Cortical Stimulation (XCS) System when used as indicated for treatment-resistant depression (TRD).

Study Overview

• Status: Not yet recruiting
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Device: Motif XCS System

Detailed Description

The Motif XCS System study is a prospective, multi-center, single-arm, open-label early feasibility study (EFS).

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ted Meehan; Email: ted.meehan@brightresearch.com
• Study Contact Backup: Name: Catherine Lapp; Phone Number: 201-381-1534; Email: cate@motifneuro.tech

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Has a diagnosis of unipolar non-psychotic Major Depressive Disorder (MDD) and is currently experiencing a major depressive episode (MDE) as defined by Diagnostic and Statistical Manual of Mental Disorders (DSM-5)
2. Has a screening Montgomery-Åsberg Depression Rating Scale (MADRS) score of ≥20
3. Has not had a sustained response to 2 or more adequately dosed antidepressant treatments from at least 2 different antidepressant treatment classes in at least one episode of major depressive disorder, according to the Antidepressant Treatment History Form (ATHF)
4. Is willing and able to provide written informed consent
5. Is 22-85 years of age
6. Is willing and able to comply with the protocol, including follow-up visits
7. Has been on a stable psychiatric treatment regimen for 30 days before the study screening MADRS and is willing to maintain a stable psychiatric treatment regimen through the Week 4 follow-up visit

Exclusion Criteria:

1. Has a cranial implant (with the exception of dental implants), neurostimulator, implanted medication pump, spinal cord stimulator, or pacemaker/implantable cardioverter-defibrillator
2. Has knowledge of planned magnetic resonance imaging (MRIs) in the next 12 months, after implant
3. Is unable to undergo imaging with computed tomography (CT), magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), or functional magnetic resonance imaging (fMRI)
4. In the opinion of the investigator, the implant and therapy pose an unacceptable surgical or medical risk to the patient
5. Is currently taking blood thinners and cannot be taken off blood thinners
6. Has taken ketamine or esketamine in the past 30 days or is planning on taking ketamine or esketamine before the 4-week follow-up visit
7. Has taken hallucinogenic or dissociative medications in the past 30 days or is planning on taking hallucinogenic or dissociative medications for the treatment of mood or anxiety disorders before the 4-week follow-up visit
8. Has a history of bipolar disorder
9. Has a history of schizophrenia, schizoaffective disorder, or other psychotic disorder
10. Has psychotic features in the current depressive episode
11. Has a chronic and clinically significant neurological disorder (epilepsy, dementia, delirium, amnestic disorder, brain tumor), or neuroimaging findings that would potentially impact the efficacy of treatment (e.g., extensive white matter disease, demyelinating lesions, atrophy, brain tumor)
12. Currently taking medication that would alter the seizure threshold, increasing potential seizure risks
13. Has a history of brain injury that resulted in current cognitive impairment
14. Has a history of bony disorders that impact the safe and effective use of the device as well as device implantation
15. Has a history of skin disorders that impact the safe and effective use of the device as well as device implantation
16. Has failed all attempts to achieve at least 50% reduction in depressive symptoms after completion of approved treatment courses of electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) for treatment of MDD
17. Is planning to receive any other neuromodulation therapy during the study
18. Meets the DSM-5 criteria for alcohol use disorder or other substance use disorder (not including tobacco/nicotine) within 12 months prior to study enrollment or, in the opinion of the investigator, is using illicit drugs recreationally or therapeutically which could impact the safety or effectiveness of the therapy
19. Female who is pregnant at the time of inclusion, or planning to become pregnant during the duration of the study, or not willing to use an effective method of birth control
20. Has a life expectancy less than 12 months
21. In the opinion of the investigator, is considered to be acutely suicidal (e.g., Type 4 or 5 on the Columbia-Suicide Severity Rating Scale [C-SSRS])
22. In the investigator's opinion, any known comorbidity that would complicate the assessment of safety or prevent participation in follow-up visits

Before implantation of the Motif Digitally Programmable Over-Brain Therapeutic (DOT) Implant, subjects must continue to meet all study eligibility criteria. Subjects must also meet the following additional criteria:

1. Psychiatric treatment regimen has remained stable
2. Has skull thickness ≥5.5 mm and ≤15.5 mm over the implant target

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Motif XCS System	Device: Motif XCS System; The Motif XCS System is a programmable device that delivers stimulation through surface electrodes implanted in a burr hole in the skull, positioned over the left dorsolateral prefrontal cortex (DLPFC), without penetrating the dura.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of device and/or procedure-related adverse events (AEs)	During procedure to 12 months follow-up

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in score on clinical outcome measures of treatment-resistant depression (Montgomery-Åsberg Depression Rating Scale [MADRS])	After treatment to 12 months follow-up
The incidence of stimulation-induced side effects	After treatment to 12 months follow-up

Collaborators and Investigators

• Sponsor: Motif Neurotech, Inc.
• Collaborators: Bright Research Partners
• Investigators: Study Director: Ted Meehan, Bright Research

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: May 8, 2026
• First Submitted That Met QC Criteria: May 14, 2026
• First Posted (Actual): May 18, 2026

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: May 14, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Depression; Treatment-resistant depression
• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Mood Disorders; Depressive Disorder; Behavior; Depression; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant
• Other Study ID Numbers: TP-27

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes