Chronic Post-Traumatic Stress Disorder
Conditions
Keywords
Quality of Life, Post-Traumatic Stress Disorder, Transcranial Magnetic Stimulation, Feasibility studies
Brief summary
The purpose of the proposed study is to evaluate initial feasibility and efficacy of Theta Burst Transcranial Magnetic Stimulation (TBS) as an adjunct treatment for Veterans with PTSD. Primary outcomes measures include a feasibility of TBS procedures, with secondary outcome measures focusing on changes in PTSD symptom severity and quality of life and social/occupation functioning.
Detailed description
The purpose of the proposed study is to evaluate the feasibility of theta burst transcranial magnetic stimulation (TBS) as an adjunct treatment for Veterans with PTSD. This project will result in development of methods needed to conduct an adequately powered, randomized controlled study of TBS for PTSD, which will assess the relationship between change in symptoms and quality of life. It will also lay the foundation for subsequent rehabilitation studies combining neuromodulation and psychotherapy in the longer term. TBS has several advantages compared to standard repetitive Transcranial Magnetic Stimulation (rTMS), including its ability to deliver large numbers of stimulation pulses in a shorter time period, and a stimulation pattern that may specifically affect key brain regions involved in PTSD. The significance of this research is the development of a novel, non-invasive brain stimulation approach for PTSD recovery. This project will provide the foundation for the development of methods needed to conduct an adequately powered, randomized controlled study of TBS for PTSD to ultimately develop brain stimulation techniques that can be combined with evidence-based psychotherapy, to develop a more powerful, individualized rehabilitation option for Veterans with PTSD.
Interventions
DEVICETheta burst stimulation
Theta burst transcranial magnetic stimulation
DEVICESham stimulation
Sham Theta burst transcranial magnetic stimulation
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of chronic PTSD according to DSM-5 criteria * Veteran (male or female) * age between 18-70 years * clinically symptomatic despite ongoing stable treatment regimens for at least 6 weeks prior to study procedures * capable of independently reading and understanding patient information materials and providing informed consent
Exclusion criteria
* Cardiac pacemaker * implanted device (deep brain stimulation) or metal in the brain * cervical spinal cord * or upper thoracic spinal cord * pregnancy/lactation, or planning to become pregnant during the study * lifetime history of moderate or severe traumatic brain injury (TBI) * current unstable medical conditions * current (or past if appropriate) significant neurological disorder, or lifetime history of: * seizure disorder * primary or secondary CNS tumors * stroke * cerebral aneurysm * primary psychotic disorder * bipolar I disorder * active moderate/severe substance use disorders (within the last month, excluding nicotine/caffeine * active suicidal intent or plan
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Retained, a Measure of Acceptability of TBS Procedures | 2 weeks | Measurement of TBS acceptability, measured using participant retention rates (all-cause discontinuation) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Quality of Life Due to TBS Treatment | Baseline and end of double-blind period (2 weeks) | Change in the quality of life, using the quality of life questionnaire QLESQ - Quality of Life Enjoyment and Satisfaction Questionnaire (General Quality of Life Index). A self-report scale covering multiple domains (physical health, subjective feelings, leisure time activities, social relationships, treatment satisfaction) The General Quality of Life Index took the mean of all domains. Scores range from 0-5, with higher scores indicating higher quality of life. |
| Change in PTSD Symptom Severity | Baseline and end of double-blind period (2 weeks) | Change in PTSD symptoms measured by the Clinician Administered PTSD Scale for DSM-5 (CAPS-5). The CAPS-5 is a structured interview to measure for PTSD symptom change and presence/absence of PTSD, items rated 0 = 'absent' to 4 = 'extreme/incapacitating,' total symptom severity score is calculated by summing severity scores for the 20 DSM-5 PTSD symptoms. Higher scores indicate more severe PTSD symptoms. |
| Change in Social/Occupational Functioning (QOL/SOF) Due to TBS Treatment | Baseline and end of double-blind period (2 weeks) | Change measured using the social/occupational functioning assessment scale (SOFAS). Clinician rating of social & occupational functioning. Scale of 0-100 with higher scores indicating higher functioning. |
Countries
United States
Participant flow
Recruitment details
Participants consented at a formal in-person eligibility determination (screening). Location: Providence, RI
Pre-assignment details
6 participants were excluded during pre-assignment. * 2 Not Eligible (1 due to the absence of Criterion A trauma, 1 declined to complete eligibility procedures) * 2 Withdrew Consent * 2 Discontinued (1 lost/unable to contact, 1 inpatient admission)
Participants by arm
| Arm | Count |
|---|---|
| Sham Stimulation Participants allocated to receive sham TBS during the double-blind period | 25 |
| Active Stimulation Participants allocated to receive active TBS during the double-blind period. | 25 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-Blind (0-2 Weeks) | Adverse Event | 1 | 0 |
| Double-Blind (0-2 Weeks) | Withdrawal by Subject | 1 | 1 |
| Follow-up | Lost to Follow-up | 1 | 1 |
| Unblinded (Optional 2-4 Weeks) | Lost to Follow-up | 0 | 1 |
| Unblinded (Optional 2-4 Weeks) | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Sham Stimulation | Active Stimulation |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 6 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 41 Participants | 19 Participants | 22 Participants |
| Age, Continuous | 51 years STANDARD_DEVIATION 12 | 53 years STANDARD_DEVIATION 12 | 49 years STANDARD_DEVIATION 13 |
| Depressive Symptom Severity | 41.02 score on a scale STANDARD_DEVIATION 11.74 | 39.20 score on a scale STANDARD_DEVIATION 11.52 | 42.84 score on a scale STANDARD_DEVIATION 11.91 |
| Education Advanced degree and/or education beyond college | 5 Participants | 3 Participants | 2 Participants |
| Education Bachelor's degree | 10 Participants | 8 Participants | 2 Participants |
| Education High school or equivalent | 7 Participants | 5 Participants | 2 Participants |
| Education Less than high school | 2 Participants | 1 Participants | 1 Participants |
| Education Multiple selections | 5 Participants | 1 Participants | 4 Participants |
| Education Some college | 18 Participants | 7 Participants | 11 Participants |
| Education Trade or vocational degree | 3 Participants | 0 Participants | 3 Participants |
| Employment Status Full time | 10 Participants | 4 Participants | 6 Participants |
| Employment Status Multiple selections | 3 Participants | 1 Participants | 2 Participants |
| Employment Status Part time | 3 Participants | 2 Participants | 1 Participants |
| Employment Status Retired | 15 Participants | 9 Participants | 6 Participants |
| Employment Status Unemployed | 19 Participants | 9 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 46 Participants | 23 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants |
| Mild Traumatic Brain Injury | 12 Participants | 5 Participants | 7 Participants |
| Military History Air Force | 3 Participants | 3 Participants | 0 Participants |
| Military History Army | 16 Participants | 8 Participants | 8 Participants |
| Military History Marines | 3 Participants | 1 Participants | 2 Participants |
| Military History Navy | 14 Participants | 6 Participants | 8 Participants |
| Military History No response | 14 Participants | 7 Participants | 7 Participants |
| Prior Brain Stimulation Electroconvulsive Therapy | 3 Participants | 1 Participants | 2 Participants |
| Prior Brain Stimulation Transcranial Magnetic Stimulation | 2 Participants | 2 Participants | 0 Participants |
| Psychiatric Comorbidity Bipolar II, most recent episode depressed | 5 Participants | 3 Participants | 2 Participants |
| Psychiatric Comorbidity Major Depressive Disorder (MDD) | 50 Participants | 25 Participants | 25 Participants |
| Psychiatric Comorbidity Opoiod use disorder | 11 Participants | 5 Participants | 6 Participants |
| Psychiatric Comorbidity Substance Use Disorder (Mild) | 27 Participants | 11 Participants | 16 Participants |
| Psychiatric History Inpatient hospitalization(s) | 28 Participants | 15 Participants | 13 Participants |
| Psychiatric History Suicide attempt(s) | 12 Participants | 6 Participants | 6 Participants |
| PTSD Symptom Severity CAPS-5 Score | 47.64 score on a scale STANDARD_DEVIATION 10.2 | 47.36 score on a scale STANDARD_DEVIATION 10.62 | 47.92 score on a scale STANDARD_DEVIATION 9.97 |
| PTSD Symptom Severity PCL-5 Score | 49.68 score on a scale STANDARD_DEVIATION 10.31 | 49.96 score on a scale STANDARD_DEVIATION 11.37 | 49.40 score on a scale STANDARD_DEVIATION 9.35 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 42 Participants | 20 Participants | 22 Participants |
| Region of Enrollment United States | 50 Participants | 25 Participants | 25 Participants |
| Sex: Female, Male Female | 8 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Male | 42 Participants | 22 Participants | 20 Participants |
| Social/Occupational Function & Quality of Life QLESQ (General Quality of Life Index) | 2.55 score on a scale STANDARD_DEVIATION 0.72 | 2.57 score on a scale STANDARD_DEVIATION 0.7 | 2.53 score on a scale STANDARD_DEVIATION 0.75 |
| Social/Occupational Function & Quality of Life SOFAS Score | 44.44 score on a scale STANDARD_DEVIATION 13.92 | 44.56 score on a scale STANDARD_DEVIATION 14.94 | 44.32 score on a scale STANDARD_DEVIATION 13.14 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 56 | 0 / 25 | 0 / 25 |
| other Total, other adverse events | 0 / 56 | 2 / 25 | 9 / 25 |
| serious Total, serious adverse events | 1 / 56 | 2 / 25 | 0 / 25 |
Outcome results
Primary
Number of Participants Retained, a Measure of Acceptability of TBS Procedures
Measurement of TBS acceptability, measured using participant retention rates (all-cause discontinuation)
Time frame: 2 weeks
Population: Data was analyzed in an intent-to-treat fashion, defined as participants that were randomized and received at least one iTBS session.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sham Stimulation | Number of Participants Retained, a Measure of Acceptability of TBS Procedures | 23 Participants |
| Active Stimulation | Number of Participants Retained, a Measure of Acceptability of TBS Procedures | 24 Participants |
Secondary
Change in PTSD Symptom Severity
Change in PTSD symptoms measured by the Clinician Administered PTSD Scale for DSM-5 (CAPS-5). The CAPS-5 is a structured interview to measure for PTSD symptom change and presence/absence of PTSD, items rated 0 = 'absent' to 4 = 'extreme/incapacitating,' total symptom severity score is calculated by summing severity scores for the 20 DSM-5 PTSD symptoms. Higher scores indicate more severe PTSD symptoms.
Time frame: Baseline and end of double-blind period (2 weeks)
Population: Included all subjects who were randomized. Primary outcomes were measured using analysis of variance to compare groups at the end of the 2-week double blind phase. Missing data was addressed using multiple imputation, with 20 imputations or maximum likelihood parameter estimation in mixed model analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sham Stimulation | Change in PTSD Symptom Severity | Baseline | 47.36 score on a scale | Standard Deviation 10.62 |
| Sham Stimulation | Change in PTSD Symptom Severity | End of Double-Blind | 39.38 score on a scale | Standard Deviation 13.77 |
| Active Stimulation | Change in PTSD Symptom Severity | Baseline | 47.92 score on a scale | Standard Deviation 9.97 |
| Active Stimulation | Change in PTSD Symptom Severity | End of Double-Blind | 38.58 score on a scale | Standard Deviation 11.42 |
p-value: 0.61ANCOVA
Secondary
Change in Quality of Life Due to TBS Treatment
Change in the quality of life, using the quality of life questionnaire QLESQ - Quality of Life Enjoyment and Satisfaction Questionnaire (General Quality of Life Index). A self-report scale covering multiple domains (physical health, subjective feelings, leisure time activities, social relationships, treatment satisfaction) The General Quality of Life Index took the mean of all domains. Scores range from 0-5, with higher scores indicating higher quality of life.
Time frame: Baseline and end of double-blind period (2 weeks)
Population: Data was analyzed in an intent-to-treat fashion. Primary outcomes were measured using analysis of variance to compare groups at the end of the 2-week double blind phase. Missing data was addressed using multiple imputation, with 20 imputations or maximum likelihood parameter estimation in mixed model analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sham Stimulation | Change in Quality of Life Due to TBS Treatment | Baseline | 2.57 score on a scale | Standard Deviation 0.7 |
| Sham Stimulation | Change in Quality of Life Due to TBS Treatment | End of Double-Blind | 2.71 score on a scale | Standard Deviation 0.8 |
| Active Stimulation | Change in Quality of Life Due to TBS Treatment | Baseline | 2.53 score on a scale | Standard Deviation 0.75 |
| Active Stimulation | Change in Quality of Life Due to TBS Treatment | End of Double-Blind | 2.81 score on a scale | Standard Deviation 0.78 |
p-value: 0.46ANCOVA
Secondary
Change in Social/Occupational Functioning (QOL/SOF) Due to TBS Treatment
Change measured using the social/occupational functioning assessment scale (SOFAS). Clinician rating of social & occupational functioning. Scale of 0-100 with higher scores indicating higher functioning.
Time frame: Baseline and end of double-blind period (2 weeks)
Population: Included all subjects who were randomized. Primary outcomes were measured using analysis of variance to compare groups at the end of the 2-week double blind phase. Missing data was addressed using multiple imputation, with 20 imputations or maximum likelihood parameter estimation in mixed model analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sham Stimulation | Change in Social/Occupational Functioning (QOL/SOF) Due to TBS Treatment | Baseline | 44.56 score on a scale | Standard Deviation 14.94 |
| Sham Stimulation | Change in Social/Occupational Functioning (QOL/SOF) Due to TBS Treatment | End of Double-Blind | 48.08 score on a scale | Standard Deviation 17.7 |
| Active Stimulation | Change in Social/Occupational Functioning (QOL/SOF) Due to TBS Treatment | Baseline | 44.32 score on a scale | Standard Deviation 13.14 |
| Active Stimulation | Change in Social/Occupational Functioning (QOL/SOF) Due to TBS Treatment | End of Double-Blind | 53.38 score on a scale | Standard Deviation 16.96 |
p-value: 0.04ANCOVA