Generalized Anxiety Disorder
Conditions
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.
Interventions
Peripheral nerve stimulation with the Empower device. The active and sham treatments only differ by the location of application on the body.
Sponsors
National Center for Complementary and Integrative Health (NCCIH)
University of Nebraska
Theranova, L.L.C.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Research staff will not provide any details that would cause participants to become unblinded to the treatment groups.
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Adherence | 6 weeks | Feasibility as assessed via treatment adherence (treatment sessions administered as a percentage of total possible) for each participant |
| Usability | 6 weeks | Acceptability as assessed via a usability assessment (System Usability Scale (SUS)). For the SUS, the score range is 0 to 100, with a higher score indicating the stimulation system's better usability. The survey includes 10 questions in which statements about the system are rated from Strongly disagree up to Strongly agree. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Device-related Adverse Events | 6 weeks | Safety assessment via device-related adverse events |
| Change in Hamilton Anxiety Rating Scale (HAM-A) Score From Baseline to 6weeks | 6 weeks | 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. |
| Change in Participant-reported Beck Anxiety Inventory (BAI) Score From Baseline to 6 Weeks | 6 weeks | Anxiety severity evaluation via participant-reported Beck Anxiety Inventory (BAI) score from Baseline to 6 weeks. For the BAI, the score range is 0 to 63, with a higher scoring meaning more severe anxiety. |
| Effective Nerve Stimulation | 6 weeks | The percentage of treatment sessions that provide effective nerve stimulation as assessed via participant-reported confirmation of tingling sensation |
| Satisfaction With Treatment | 6 weeks | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Participant Blinding to Treatment Group at 6 Weeks | 6 weeks | Participant blinding to treatment group will be assessed. All participants will be asked if they believe that they have received the real treatment, with possible responses of Yes, No, or Don't Know. Then, for the active and sham treatment groups, the blinding index will be calculated, where the blinding index can range from -1 to 1. A score of 1 means that all participants have guessed correctly about group assignment, a score of -1 means that all participants have guessed incorrectly about group assignment. |
Countries
United States
Participant flow
Recruitment details
18 participants signed the Informed Consent Form and screened. 12 Subjects were fully enrolled.
Pre-assignment details
Of 18 subjects that signed the Informed Consent, 6 did not meet all of the Inclusion/Exclusion criteria before randomization to a study arm. Therefore, only 12 subjects were fully enrolled and randomized into the trial.
Participants by arm
| Arm | Count |
|---|---|
| Active Treatment 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.
Empower Neuromodulation System: Peripheral nerve stimulation with the Empower device. The active and sham treatments only differ by the location of application on the body. | 6 |
| Sham Treatment 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.
Empower Neuromodulation System: Peripheral nerve stimulation with the Empower device. The active and sham treatments only differ by the location of application on the body. | 6 |
| Total | 12 |
Baseline characteristics
| Characteristic | Active Treatment | Sham Treatment | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 6 Participants | 12 Participants |
| Age, Continuous | 44 Years | 41 Years | 41 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 6 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 5 Participants | 6 Participants | 11 Participants |
| Region of Enrollment United States | 6 Participants | 6 Participants | 12 Participants |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 9 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 1 / 6 | 2 / 6 |
| serious Total, serious adverse events | 0 / 6 | 1 / 6 |
Outcome results
Primary
Treatment Adherence
Feasibility as assessed via treatment adherence (treatment sessions administered as a percentage of total possible) for each participant
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Treatment | Treatment Adherence | 82 Percentage of Treatment Sessions | Standard Deviation 19 |
| Sham Treatment | Treatment Adherence | 72 Percentage of Treatment Sessions | Standard Deviation 29 |
Primary
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 score indicating the stimulation system's better usability. The survey includes 10 questions in which statements about the system are rated from Strongly disagree up to Strongly agree.
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Treatment | Usability | 73 Units on a scale | Standard Deviation 19 |
| Sham Treatment | Usability | 77 Units on a scale | Standard Deviation 19 |
Secondary
Change in Hamilton Anxiety Rating Scale (HAM-A) Score From Baseline to 6weeks
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.
Time frame: 6 weeks
Population: Change in HAM-A score from Baseline to 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Treatment | Change in Hamilton Anxiety Rating Scale (HAM-A) Score From Baseline to 6weeks | -6.0 Score | Standard Deviation 9.4 |
| Sham Treatment | Change in Hamilton Anxiety Rating Scale (HAM-A) Score From Baseline to 6weeks | -12.2 Score | Standard Deviation 4.5 |
Secondary
Change in Participant-reported Beck Anxiety Inventory (BAI) Score From Baseline to 6 Weeks
Anxiety severity evaluation via participant-reported Beck Anxiety Inventory (BAI) score from Baseline to 6 weeks. For the BAI, the score range is 0 to 63, with a higher scoring meaning more severe anxiety.
Time frame: 6 weeks
Population: Change in BAI score from Baseline to 6 week visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Treatment | Change in Participant-reported Beck Anxiety Inventory (BAI) Score From Baseline to 6 Weeks | -2.8 Score | Standard Deviation 9.4 |
| Sham Treatment | Change in Participant-reported Beck Anxiety Inventory (BAI) Score From Baseline to 6 Weeks | -2 Score | Standard Deviation 5.8 |
Secondary
Effective Nerve Stimulation
The percentage of treatment sessions that provide effective nerve stimulation as assessed via participant-reported confirmation of tingling sensation
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Treatment | Effective Nerve Stimulation | 98 % of treatments that felt skin tingling | Standard Deviation 2 |
| Sham Treatment | Effective Nerve Stimulation | 100 % of treatments that felt skin tingling | Standard Deviation 1 |
Secondary
Number of Participants With Device-related Adverse Events
Safety assessment via device-related adverse events
Time frame: 6 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Treatment | Number of Participants With Device-related Adverse Events | 0 Participants |
| Sham Treatment | Number of Participants With Device-related Adverse Events | 1 Participants |
Secondary
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.
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Treatment | Satisfaction With Treatment | 52 VAS score | Standard Deviation 25 |
| Sham Treatment | Satisfaction With Treatment | 42 VAS score | Standard Deviation 22 |
Other Pre-specified
Participant Blinding to Treatment Group at 6 Weeks
Participant blinding to treatment group will be assessed. All participants will be asked if they believe that they have received the real treatment, with possible responses of Yes, No, or Don't Know. Then, for the active and sham treatment groups, the blinding index will be calculated, where the blinding index can range from -1 to 1. A score of 1 means that all participants have guessed correctly about group assignment, a score of -1 means that all participants have guessed incorrectly about group assignment.
Time frame: 6 weeks
Population: Blinding Index at 6 week visit
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Active Treatment | Participant Blinding to Treatment Group at 6 Weeks | -0.4 Index |
| Sham Treatment | Participant Blinding to Treatment Group at 6 Weeks | -0.17 Index |