Regulated Stimulation for Optimized Network Activity and Therapeutic Equilibrium

Overview

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).

Detailed description

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

Interventions

• 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.

Primary outcome measures

• Incidence of device and/or procedure-related adverse events (AEs) [Time frame: During procedure to 12 months follow-up]

Secondary outcome measures (2)

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

Eligibility criteria

Inclusion criteria

• 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)
• Has a screening Montgomery-Åsberg Depression Rating Scale (MADRS) score of ≥20
• 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)
• Is willing and able to provide written informed consent
• Is 22-85 years of age
• Is willing and able to comply with the protocol, including follow-up visits
• 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

• Has a cranial implant (with the exception of dental implants), neurostimulator, implanted medication pump, spinal cord stimulator, or pacemaker/implantable cardioverter-defibrillator
• Has knowledge of planned magnetic resonance imaging (MRIs) in the next 12 months, after implant
• Is unable to undergo imaging with computed tomography (CT), magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), or functional magnetic resonance imaging (fMRI)
• In the opinion of the investigator, the implant and therapy pose an unacceptable surgical or medical risk to the patient
• Is currently taking blood thinners and cannot be taken off blood thinners
• 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
• 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
• Has a history of bipolar disorder
• Has a history of schizophrenia, schizoaffective disorder, or other psychotic disorder
• Has psychotic features in the current depressive episode
• 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)
• Currently taking medication that would alter the seizure threshold, increasing potential seizure risks
• Has a history of brain injury that resulted in current cognitive impairment
• Has a history of bony disorders that impact the safe and effective use of the device as well as device implantation
• Has a history of skin disorders that impact the safe and effective use of the device as well as device implantation
• 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
• Is planning to receive any other neuromodulation therapy during the study
• 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
• 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
• Has a life expectancy less than 12 months
• 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 \[C-SSRS\])
• 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:

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07594483 · TP-27

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗