Post Traumatic Stress Disorder
Conditions
Keywords
Transcranial Magnetic Stimulation, PTSD, Biomarkers, Neuroimaging, Psychophysiology
Brief summary
The study will (1) assess feasibility of a TMS treatment in an underserved population; (2) determine if this TMS treatment protocol improves PTSD symptoms and biological markers of PTSD such as brain functioning and startle responses; (3) define new brain targets for future TMS studies; (4) provide the first data for individual differences, which will help personalize treatment for PTSD patients; (5) improve knowledge of the neurobiology of PTSD and treatment response.
Detailed description
Posttraumatic stress disorder is a psychiatric disorder that can develop in response to a traumatic event, and half of civilians living in inner-city areas with high levels of violence suffer from PTSD. The currently recommended treatment for PTSD is focused on discussing the trauma, but a third to half of patients cannot participate or do not benefit from this treatment, especially individuals with low levels of education or literacy. Therefore, new treatments for PTSD are needed. The study will (1) assess feasibility of a TMS treatment in an underserved population; (2) determine if this TMS treatment protocol improves PTSD symptoms and biological markers of PTSD such as brain functioning and startle responses; (3) define new brain targets for future TMS studies; (4) provide the first data for individual differences, which will help personalize treatment for PTSD patients; (5) improve knowledge of the neurobiology of PTSD and treatment response.
Interventions
DEVICETranscranial Magnetic Stimulation (TMS)
10-day treatment (2 per day with 10 minute break, 20 sessions in total) of active Transcranial Magnetic Stimulation (TMS). TMS is a noninvasive treatment that uses magnetic fields to induce a small electric current in specific brain regions.
10-day treatment (2 per day with 10 minute break, 20 sessions in total) of sham control.
Sponsors
Emory University
National Institute of Mental Health (NIMH)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Men and women 18-65 years of age. * Meet for partial PTSD, defined as 3 out of 4 symptom clusters always including cluster E (alterations in arousal and reactivity) according to the DSM-5 criteria using the Clinician-Administered PTSD Scale (CAPS-5). * Capable and willing to provide informed consent. * Able to adhere to the treatment schedule.
Exclusion criteria
* Having active suicidal intent or plan as defined by a positive answer to questions 4 and/or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS): Screening version; or in the clinician's opinion, is likely to attempt suicide within the next six months. * Unstable psychotropic medication status. Participants taking psychotropic medications (i.e.,antidepressants, antipsychotics, benzodiazepines and anticonvulsants, etc.) can be enrolled in the study as long as medication type and dose has been stable for at least 6 weeks, and additionally, medication type or dose does not change during the course of the study. * Lifetime diagnosis of psychotic disorder or bipolar I disorder per diagnostic interview. * Diagnosed with the following conditions: a neurological disorder, including a history of seizures, cerebrovascular disease, primary or secondary tumors in CNS, stroke, cerebral aneurysm or movement disorder or any lifetime history of loss of consciousness for more than 5 minutes due to head injury. * History of cranial surgery, metallic particles in the eye or head (exclusive of mouth), implanted cardiac pacemaker or any intra-cardiac lines, implanted neurostimulators, intra-cranial implants (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or implanted medical pumps. * Current substance abuse or dependence as indicated by a score of 6 or higher on the Drug Abuse Screening Test (DAST). * Current alcohol abuse or dependence as indicated by a score of 8 or higher on the Alcohol Use Disorder Identification Test (AUDIT). * Being pregnant or a positive pregnancy test at the beginning of each TMS treatment week for sexually active women of childbearing age who are on reliable birth control. * Currently participating in another clinical study or enrolled in another clinical study within 30 days prior to this study or started (new) treatment for PTSD within 3 months prior to this study. * Previously treated with TMS.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Amygdala Reactivity During Fear Processing Pre- to Post-treatment | Baseline, day 10 | Amygdala reactivity during fear processing were assessed by fMRI responses as participants viewed 15 blocks each of fearful face and neutral face stimuli, while amygdala reactivity was measured. The amygdala was separated in the right and left hemispheres. fMRI measures the blood oxygen level-dependent response, a measure of how much more oxygenated blood there is in a certain brain region, which reflects activation of the brain region. A regression model was used to determine the beta value as a measure of brain activity. Across voxels in each region (right amygdala, left amygdala), the beta value for response in the amygdala to Fearful faces and Neutral faces was extracted. |
| Change in Skin Conductance Response to Trauma Cues Pre- to Post-treatment | Baseline, day 10 | Change in skin conductance response to trauma cues pre- to post-treatment was assessed. The mobile skin conductance response was measured in microsiemens when participants described their worst trauma, followed by assessment of their symptoms. A numeric value estimating the skin conductance response was calculated by subtracting the baseline skin conductance reactivity from the reactivity during the trauma description. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Inhibition-related Activation in the Ventromedial Prefrontal Cortex (vmPFC) Pre- to Post-treatment | Baseline, day 10 | Change in inhibition-related activation in the vmPFC was assessed by fMRI responses as participants viewed 15 blocks each of fearful face and neutral face stimuli. At the same time, reactivity in the ventromedial prefrontal cortex was measured. Across voxels in the ventromedial prefrontal cortex, a contrast estimate of responses to Fearful \> Neutral faces was extracted. This is being reported as a numeric value estimating inhibition-related brain activation (contrast estimate fear versus neutral) |
| Change in Inhibition-related Activation in the Hippocampus Pre- to Post-treatment | Baseline, day 10 | Change in inhibition-related activation in the hippocampus was assessed by fMRI responses as participants viewed 15 blocks each of fearful face and neutral face stimuli, while hippocampal reactivity was measured. The hippocampus was separated into the right and left hemispheres. Across voxels in each region (right hippocampus, left hippocampus), a contrast estimate of Fearful \> Neutral faces was extracted. |
| Change in Ventromedial Prefrontal Cortex (vmPFC)-Amygdala Functional Connectivity Pre- to Post-treatment | Baseline, day 10 | Change in vmPFC-amygdala functional connectivity pre- to post-treatment was assessed. A numeric value estimating the correlation between the vmPFC and amygdala was measured. |
| Change in Dorsolateral Prefrontal Cortex (DLPFC)-Amygdala Functional Connectivity Pre- to Post-treatment | Baseline, day 10 | Change in DLPFC-amygdala functional connectivity pre- to post-treatment was assessed. A numeric value estimating the correlation between the DLPFC and amygdala was measured. |
| Change in Fear-Potentiated Startle Responses to Danger and Safety Cues Pre- to Post-treatment. | Baseline, day 10 (Post TMS) | Change in Fear-Potentiated Startle Responses to danger and safety cues pre- to post-treatment was assessed. An eye blink response was measured using electromyography with sensors placed near the eyes. Symbols were presented on a screen, one symbol followed by an airblast to the throat was the danger cue and a different symbol not followed by the airblast was the safety cue. The eye blink response in response to danger and safety cues was measured. |
| Change in Discrimination Between Danger and Safety Cues Pre- to Post-treatment | Baseline, day 10 | Change in discrimination between danger and safety cues pre- to post-treatment was assessed. An eye blink response was measured using electromyography with sensors placed near the eyes. Symbols were presented on a screen, with one symbol followed by an airblast to the throat serving as the danger cue, and a different symbol, not followed by the airblast, serving as the safety cue. The eye blink response in response to danger and safety cues was measured. The difference score for the eye blink response to danger and safety was calculated. |
| Change in Post-traumatic Stress Disorder (PTSD) Hyperarousal Symptoms Pre- to Post-treatment | Baseline, day 10 | The severity of self-reported PTSD hyperarousal symptoms was assessed with the PCL-5, sub-cluster E. The PCL-5 asks participants to recall the worst stressful event that is currently bothering them the most. Keeping this event in mind, participants respond to 20 questions indicating how bothered they have been by PTSD symptoms. Responses are on a 5-point scale, where 0 = not bothered at all and 4 = extremely bothered. The 6 questions related to hyperarousal were used. Total raw scores range from 0 to 24, where higher scores indicate greater distress from PTSD hyperarousal symptoms. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORSanne van Rooij, PhD
Emory University
Participant flow
Recruitment details
After confirming eligibility (≥3 DSM-5 PTSD criteria using CAPS-5), 5 participants were excluded for not meeting PTSD criteria, 1 for Bipolar I on diagnostic assessment, and 2 for neurological exclusions. Additionally, 5 participants withdrew before randomization. A total of 50 participants were randomized to active or sham TMS.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 30 Participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 24 |
| other Total, other adverse events | 7 / 26 | 4 / 24 |
| serious Total, serious adverse events | 0 / 26 | 0 / 24 |
Outcome results
None listed