PTSD
Conditions
Keywords
safety memory, PTSD, tDCS, ventromedial prefrontal cortex, fear conditioning, context processing
Brief summary
The primary purpose of this study is to investigate the effects of tDCS timing on extinction memory in PTSD. A total of 90 participants will be randomized equally across one of three groups: 1. One group receiving active stimulation during extinction followed by sham stimulation during consolidation 2. One group receiving sham stimulation during extinction followed by active stimulation during consolidation 3. One group receiving sham stimulation both during extinction and consolidation This study also includes an online sub-study (Aim 2) focused on contextual processing along the PTSD spectrum. The online study tests if there is an association between threat and non-threat learning in contextual and non-contextual situations. A maximum of 500 participants will be recruited using an online, panel-based platform.
Detailed description
This is a three-arm study composed of four to five visits over an approximate period of three weeks. Up to ninety participants are exposed to a fear conditioning, extinction, and extinction memory paradigm at three separate study visits (day 3-5); one of these study visits will include active or sham transcranial direct current stimulation (tDCS) for a period of 15 minutes. Skin conductance reactivity during extinction memory (day 5) is the primary outcome. Additional study procedures include a screening period (day 1) and two optional MRI scans, one done on study day 2 and one done on study day 5. As the completion of MRI scans are an optional study component, MRI-related data is not reported here. SUB-STUDY: The objective of this sub-study is to test performance differences between contextual and non-contextual processing in individuals across the PTSD spectrum using an online, panel-based platform. Following a within-subjects study design, up to 500 adult participants, 18-89 years, will be asked to complete experimental tasks that assess contextual (configural) and non-contextual (elemental) threat and non-threat learning. They will also provide demographic information (age, sex, ethnicity) and complete questionnaires assessing self-reported PTSD, anxiety, and depression severity. As this sub-study does not reflect a randomized clinical trial (no groups, no randomization, no intervention), no further information is reported here.
Interventions
DEVICEtranscranial direct current stimulation
Active tDCS will consist of 15 minutes of 2 mA intensity once, either applied during or after extinction learning.
Sponsors
National Institute of General Medical Sciences (NIGMS)
Butler Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
Individuals deemed eligible for the study will be randomized to 1) receiving active tDCS during extinction learning; sham during extinction consolidation, 2) receiving sham during extinction learning; active tDCS during extinction consolidation, 3) receiving sham during extinction learning; sham during extinction consolidation. (Anticipated enrollment: 90 participants).
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Primary diagnosis of PTSD, assessed by the Structured Clinical Interview of DSM-5 (SCID); 2. aged 18-70; 3. ability to speak, read, write, and understand English sufficiently well to complete study procedures and provide informed consent; 4. Stable psychiatric medication use or treatment for at least 6 weeks.
Exclusion criteria
1. Lifetime history of psychotic or bipolar disorder; 2. Current moderate or severe substance use disorder; if mild, not under the influence at time of study participation; 3. Acute suicidal or homicidal ideation as detected on screening instruments or in the investigator team's opinion, is likely to attempt suicide within 6 months; 4. current (or past) significant neurological disorder, injury, or other intracranial pathology including severe traumatic brain injury or lifetime history of a) seizure disorder b) primary or secondary CNS tumors c) stroke or d) cerebral aneurysm; 5. lifetime history of moderate or, current unstable medical conditions; 6. Any problems that would interfere with study participation, including MRI- or tDCS-related contraindications (e.g., implanted metallic devices/substances, metallic tattoos, pregnancy, claustrophobia, holes in the skull, skin abnormalities under stimulation sites), or indication of colorblindness, or presence of any other condition or circumstance that, in the opinion of the investigator team, has the potential to prevent study completion and/or inability to schedule visit days within the allotted time, and/or to have a confounding effect on outcome assessments.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Skin Conductance Responses | Study visit day 4: during administration of fear extinction memory. | Main protocol: Threat reactivity as quantified by skin conductance responses to a conditioned and subsequently extinguished stimulus versus a never conditioned stimulus. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Then Sham Transcranial Direct Current Stimulation Participants received 2mA transcranial direct current stimulation (tDCS) during extinction learning of conditioned threat, followed by sham tDCS for the same duration | 19 |
| Sham Then Active Transcranial Direct Current Stimulation Participants received sham transcranial direct current stimulation (tDCS) during extinction learning of conditioned threat, followed by active, 2mA tDCS | 20 |
| Sham Then Sham Transcranial Direct Current Stimulation Participants received sham transcranial direct current stimulation (tDCS) during extinction learning of conditioned threat, followed by sham tDCS | 23 |
| Total | 62 |
Baseline characteristics
| Characteristic | Active Then Sham Transcranial Direct Current Stimulation | Sham Then Active Transcranial Direct Current Stimulation | Sham Then Sham Transcranial Direct Current Stimulation | Total |
|---|---|---|---|---|
| Age, Continuous | 45.2 years STANDARD_DEVIATION 14.7 | 46.9 years STANDARD_DEVIATION 15.5 | 43.7 years STANDARD_DEVIATION 16.6 | 45.2 years STANDARD_DEVIATION 15.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 20 Participants | 20 Participants | 59 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Posttraumatic Stress Disorder (PTSD) Checklist for DSM-5 | 48.00 Average score on the PCL-5 STANDARD_DEVIATION 12.34 | 44.80 Average score on the PCL-5 STANDARD_DEVIATION 14.48 | 41.98 Average score on the PCL-5 STANDARD_DEVIATION 15.52 | 44.73 Average score on the PCL-5 STANDARD_DEVIATION 14.26 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 17 Participants | 19 Participants | 18 Participants | 54 Participants |
| Sex: Female, Male Female | 15 Participants | 13 Participants | 21 Participants | 49 Participants |
| Sex: Female, Male Male | 4 Participants | 7 Participants | 2 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 20 | 0 / 23 |
| other Total, other adverse events | 16 / 19 | 18 / 20 | 19 / 23 |
| serious Total, serious adverse events | 0 / 19 | 0 / 20 | 0 / 23 |
Outcome results
Primary
Skin Conductance Responses
Main protocol: Threat reactivity as quantified by skin conductance responses to a conditioned and subsequently extinguished stimulus versus a never conditioned stimulus.
Time frame: Study visit day 4: during administration of fear extinction memory.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active tDCS During Extinction Learning Followed by Sham tDCS During Consolidation | Skin Conductance Responses | 0.075 Skin conductance in microsiemens | Standard Error 0.025 |
| Sham tDCS During Extinction Followed by Active tDCS During Consolidation | Skin Conductance Responses | 0.088 Skin conductance in microsiemens | Standard Error 0.026 |
| Sham tDCS During Extinction Followed by Sham tDCS During Consolidation | Skin Conductance Responses | 0.057 Skin conductance in microsiemens | Standard Error 0.025 |
Comparison: Comparison of groups (3) on skin conductance reactivity to the previously extinguished stimulus versus never conditioned stimulus during extinction recallp-value: 0.02Mixed Models Analysis