Generalized Anxiety Disorder
Conditions
Brief summary
This study is investigating a new indication of Transcranial Magnetic Stimulation (TMS) by conducting a pilot randomized-controlled trial (RCT) comparing structural neuronavigation-directed TMS to Sham-TMS Placebo therapy for treatment of Generalized Anxiety Disorder (GAD).
Detailed description
Participants will complete structural MRI for neuronavigation. Participants will be randomly assigned to treatment condition. TMS or Sham-TMS sessions will occur daily 5 days/week for 6 weeks. Assessments will occur at pretreatment, weekly during treatment, post-treatment, and 3 month.
Interventions
DEVICETMS
Treatment will entail daily (5 days/week) sessions of TMS for 6 weeks.
Sponsors
Neuronetics
Hartford Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed with GAD as the principal or co-principal disorder * Clinical Global Impression Score ≥ 4 * Hamilton Anxiety Rating Scale ≥ 18 * Hamilton Rating Scale for Depression ≤ 17 * Fluency in English * Capacity to understand the nature of the study and willingness to sign informed consent form.
Exclusion criteria
* History of epilepsy or head trauma (LOC \> 5 minutes) within the past 6 months. * Lifetime history of increased intracranial pressure, seizure disorder, stroke, brain tumor, multiple sclerosis, or brain surgery. * A review of patient medications by the study physician indicates an increased risk of seizure. * An active autoimmune, endocrine, viral, or vascular disorder affecting the brain; any unstable cardiac disease; hypertension; or severe renal or liver insufficiency. * Substance use disorder or PTSD within the past 6 months. * Lifetime bipolar disorder, obsessive-compulsive disorder (OCD), psychotic disorder, mental retardation, or pervasive developmental disorder. * Any psychotic features, including dementia or delirium. Concurrent psychotherapy and unwillingness to discontinue * Medication change within past 3 months. * Current serious suicidal or homicidal ideation, and/or serious suicidal attempt within past 6 months. * Serious, unstable, or terminal medical condition or clinically judged too psychiatrically unstable to participate in the study. * Any contraindication for participation in MRI scan
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) at Post-treatment and 3-month Follow-up. | Pretreatment, Post-treatment (6 weeks after pretreatment), 3-month follow-up | Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) scores range from 0-56 with higher scores indicating more severe anxiety. |
| Responder Status | Post-treatment, 6 weeks | Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) scores range from 0-56 with higher scores indicating more severe anxiety. Responder status was defined as a ≥ 50% improvement (i.e., reduction) in SIGH-A scores from pre-treatment to post-treatment. |
| Remission Status | post-treatment, 6 weeks | Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) scores range from 0-56 with higher scores indicating more severe anxiety. Remission status was defined as a SIGH-A score \< 8 and Clinical Global Impression Improvement score = 1 (very much improved) or 2 (much improved) at post-treatment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TMS Therapy TMS treatment
TMS: Treatment will entail daily (5 days/week) sessions of TMS for 6 weeks.
Treatment in the substudy will entail 2 days/week sessions of TMS for 5 weeks. | 13 |
| TMS-Sham This is a sham TMS condition
TMS: Treatment will entail daily (5 days/week) sessions of TMS for 6 weeks.
Treatment in the substudy will entail 2 days/week sessions of TMS for 5 weeks. | 12 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 3-month Follow-up | Lost to Follow-up | 0 | 1 |
| Treatment Period | Adverse Event | 1 | 1 |
| Treatment Period | Protocol Violation | 3 | 1 |
| Treatment Period | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | TMS Therapy | TMS-Sham | Total |
|---|---|---|---|
| Age, Continuous | 44.00 years STANDARD_DEVIATION 11.95 | 44.58 years STANDARD_DEVIATION 14.75 | 44.28 years STANDARD_DEVIATION 13.09 |
| Region of Enrollment United States | 13 participants | 12 participants | 25 participants |
| Sex: Female, Male Female | 11 Participants | 8 Participants | 19 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 13 | 11 / 12 |
| serious Total, serious adverse events | 1 / 13 | 0 / 12 |
Outcome results
Primary
Change in the Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) at Post-treatment and 3-month Follow-up.
Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) scores range from 0-56 with higher scores indicating more severe anxiety.
Time frame: Pretreatment, Post-treatment (6 weeks after pretreatment), 3-month follow-up
Population: Intent-to-treat sample (n = 25)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TMS-Treatment | Change in the Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) at Post-treatment and 3-month Follow-up. | pre-treatment | 25.31 units on a scale | Standard Deviation 5.23 |
| TMS-Treatment | Change in the Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) at Post-treatment and 3-month Follow-up. | post-treatment | 12.10 units on a scale | Standard Deviation 5.77 |
| TMS-Treatment | Change in the Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) at Post-treatment and 3-month Follow-up. | 3-month follow-up | 10.36 units on a scale | Standard Deviation 7.86 |
| TMS-Sham | Change in the Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) at Post-treatment and 3-month Follow-up. | pre-treatment | 20.75 units on a scale | Standard Deviation 3.72 |
| TMS-Sham | Change in the Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) at Post-treatment and 3-month Follow-up. | post-treatment | 14.38 units on a scale | Standard Deviation 4.78 |
| TMS-Sham | Change in the Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) at Post-treatment and 3-month Follow-up. | 3-month follow-up | 17.95 units on a scale | Standard Deviation 7.48 |
p-value: 0.006ANOVA
Primary
Remission Status
Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) scores range from 0-56 with higher scores indicating more severe anxiety. Remission status was defined as a SIGH-A score \< 8 and Clinical Global Impression Improvement score = 1 (very much improved) or 2 (much improved) at post-treatment.
Time frame: post-treatment, 6 weeks
Population: Post-treatment completers
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TMS-Treatment | Remission Status | 3 participants |
| TMS-Sham | Remission Status | 1 participants |
Primary
Remission Status
Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) scores range from 0-56 with higher scores indicating more severe anxiety. Remission status was defined as a SIGH-A score \< 8 and Clinical Global Impression Improvement score = 1 (very much improved) or 2 (much improved) at 3-month follow-up.
Time frame: 3-month follow-up
Population: 3-month follow-up completers
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TMS-Treatment | Remission Status | 6 participants |
| TMS-Sham | Remission Status | 0 participants |
Primary
Responder Status
Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) scores range from 0-56 with higher scores indicating more severe anxiety. Responder status was defined as a ≥ 50% improvement (i.e., reduction) in SIGH-A scores from pre-treatment to post-treatment.
Time frame: Post-treatment, 6 weeks
Population: Post-treatment completers
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TMS-Treatment | Responder Status | 7 participants |
| TMS-Sham | Responder Status | 2 participants |
Primary
Responder Status
Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) scores range from 0-56 with higher scores indicating more severe anxiety. Responder status was defined as a ≥ 50% improvement (i.e., reduction) in SIGH-A scores from pre-treatment to 3-month follow-up.
Time frame: 3-month follow-up
Population: 3-month follow-up completers
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TMS-Treatment | Responder Status | 7 participants |
| TMS-Sham | Responder Status | 0 participants |