Empower Neuromodulation System - Pilot Study for Anxiety Treatment

Study Overview
=================
Brief Summary
-----------------
This study evaluates the effects of peripheral nerve stimulation on anxiety levels in participants with Generalized Anxiety Disorder (GAD). This is a pilot investigation in which participants will randomized (1:1) to the active or sham treatment.

Detailed Description
-----------------
Generalized anxiety disorder (GAD) is a chronic, recurring condition that affects approximately 6.4 million American adults each year. GAD is one of the most common anxiety disorders and is costly to treat. First-line treatments for GAD include medication (e.g. SSRIs, SNRIs), cognitive behavioral therapy, or both in combination. Peripheral nerve stimulation via acupuncture has been shown to directly decrease clinical anxiety scores. The investigators have developed the Empower Neuromodulation System, a non-invasive, portable transcutaneous electrical nerve stimulation (TENS) device intended to stimulate peripheral nerves for the treatment of anxiety. In this study, a randomized, controlled study will be conducted in participants with GAD. Participants will self-administer twice daily treatments with the Empower device. In this pilot study, the primary endpoints will be feasibility and acceptability, with safety and effectiveness evaluated as exploratory endpoints.

Official Title
-----------------
Pilot Evaluation of the Empower Neuromodulation System for Anxiety Treatment

Conditions
-----------------
Generalized Anxiety Disorder

Intervention / Treatment
-----------------
* Device: Empower Neuromodulation System


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: ≥19 years old Current diagnosis of GAD per DSM-5 via M.I.N.I. assessment by clinician Hamilton Anxiety Rating Scale (HAM-A) ≥18 Negative urine pregnancy test at screening (females only) Able to provide informed consent Capable and willing to follow all study-related procedures Exclusion Criteria: Has current (past 30 days) psychotic or bipolar disorder, homicidal ideation, psychiatric hospitalization, or moderate/severe substance use disorders per clinician assessment via M.I.N.I. Hamilton Depression Rating Scale (HAM-D) ≥18 PTSD Checklist for DSM-5 (PCL-5) ≥51 Exhibits suicidal intent as confirmed on the Columbia-Suicide Severity Rating Scale-Revised (C-SSRS-R) with a Yes response to question 4 or question 5 or to question 6 in the past 3 months. Changes in psychoactive medications in the past 30 days (including but not limited to psychotropic medications, thyroid hormone medication, steroids), with the exception of benzodiazepines If regularly taking benzodiazepines, has had changes in benzodiazepine dosing in the past 30 days or average use >2 days per week Psychotherapy was initiated or discontinued in the past 30 days or psychotherapy modality was changes in the past 30 days Has a history of epilepsy or a seizure disorder Has been diagnosed with peripheral nerve damage of the arm or hand or has numbness or tingling in the arm or hand at least weekly Is currently pregnant or breastfeeding, has been pregnant within the past 6 months or intends to become pregnant during the study period Currently has an active implant and/or an electrical or neurostimulator device, including but not limited to cardiac pacemaker or defibrillator, vagal neurostimulator, deep brain stimulator, spinal stimulator, sacral stimulator, bone growth stimulator, or cochlear implant Has an electrically conductive metal object (e.g. jewelry) that cannot be removed from the upper extremities and will directly contact the gel electrodes of the Empower Neuromodulation System at the active or sham anatomic location Has an open incision, wound, scar, active infection or otherwise compromised skin that will directly contact the gel electrodes of the Empower Neuromodulation System at either the active or sham anatomic location Does not have daily access to an electrical outlet for charging the investigational device and associated smartphone Has used of an investigational drug/device therapy within the past four weeks Unable to provide informed written consent Has any medical condition that would, in the opinion of the investigator, make the participant ineligible

Ages Eligible for Study
-----------------
Minimum Age: 19 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: At enrollment, participants will be randomized (1:1) to receive either the active or sham treatment for the duration of the 6-week study.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active treatment<br>Participants will self-administer treatment with the Empower device at the active treatment anatomic location twice daily for six weeks. Treatment adherence will be assessed and participants will complete surveys to evaluate the feasibility and acceptability Empower active treatment. | Device: Empower Neuromodulation System<br>* Peripheral nerve stimulation with the Empower device. The active and sham treatments only differ by the location of application on the body.<br>|
| Sham Comparator: Sham treatment<br>Participants will self-administer treatment with the Empower device at the sham treatment anatomic location twice daily for six weeks. Treatment adherence will be assessed and participants will complete surveys to evaluate the feasibility and acceptability Empower sham treatment. | Device: Empower Neuromodulation System<br>* Peripheral nerve stimulation with the Empower device. The active and sham treatments only differ by the location of application on the body.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment adherence | Feasibility as assessed via treatment adherence (treatment sessions administered as a percentage of total possible) for each participant | 6 weeks | 
| Usability | Acceptability as assessed via a usability assessment (System Usability Scale (SUS)). For the SUS, the score range is 0 to 100, with a higher scoring meaning better usability. | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effective nerve stimulation | The percentage of treatment sessions that provide effective nerve stimulation as assessed via participant-reported confirmation of tingling sensation | 6 weeks | 
| Satisfaction with treatment | The overall satisfaction with treatment (via 100-mm Visual-Analog Scale (VAS)). For the VAS, the score range is 0 to 100, with a higher scoring meaning higher satisfaction. | 6 weeks | 
| Device-related adverse events | Safety assessment via device-related adverse events | 6 weeks | 
| Clinician-assessed anxiety severity | Anxiety severity evaluation via clinician-administered Hamilton Anxiety Rating Scale (HAM-A) score. For the HAM-A, the score range is 0 to 56, with a higher scoring meaning more severe anxiety. | 6 weeks | 
| Participant-reported anxiety severity | Anxiety severity evaluation via participant-reported Beck Anxiety Inventory (BAI) score. For the BAI, the score range is 0 to 63, with a higher scoring meaning more severe anxiety. | 6 weeks | 
| Responder rate | Percentage of participant who experience ≥50% reduction in HAM-A score from enrollment to study completion | 6 weeks |