Posttraumatic Stress Disorder (PTSD)
Conditions
Keywords
Transcranial Magnetic Stimulation, Posttraumatic Stress Disorder, Veterans, Precision Medicine
Brief summary
This study is testing a personalized form of brain stimulation called PrTMS as a treatment for post-traumatic stress disorder (PTSD) in military service members and veterans. Unlike standard approaches, this treatment uses a simple brainwave test (EEG) to tailor the therapy to each individual. Participants will be randomly assigned to receive either active treatment or a comparison (sham) treatment over 6 weeks. Researchers will track changes in PTSD symptoms, mood, sleep, and overall well-being, including using wearable devices to measure things like sleep and heart rate. The goal is to see whether this personalized approach can provide greater and longer-lasting relief for individuals living with PTSD.
Detailed description
This study is a randomized, double-blind, sham-controlled trial evaluating a personalized approach to repetitive transcranial magnetic stimulation (PrTMS) for the treatment of post-traumatic stress disorder (PTSD) in military service members and veterans. PrTMS integrates spectral electroencephalography (sEEG) with neurocognitive assessments to individualize stimulation parameters, including frequency and intensity, and to allow for dynamic adjustment over the course of treatment based on each participant's evolving neurophysiological profile. Participants will undergo a 6-week treatment protocol (5 sessions per week), followed by longitudinal assessments over 6 months to evaluate durability of response. Multimodal outcomes will include clinician-administered and self-report measures of PTSD, mood, anxiety, and sleep, as well as physiologic and behavioral data collected via wearable devices. This study is designed to determine whether EEG-guided, precision neuromodulation improves clinical outcomes compared to standard, non-personalized stimulation approaches and to inform the development of individualized treatment strategies in PTSD.
Interventions
DEVICETranscranial Magnetic Stimulation
Personalized repetitive transcranial magnetic stimulation (PrTMS) is delivered using the Neurocare Apollo TMS Therapy System for 30 minutes per session, 5 days per week, over 6 weeks. Stimulation parameters (frequency 8-13 Hz and intensity typically 50-60% of motor threshold) are individualized based on baseline and serial spectral EEG (sEEG) assessments, with adjustments made throughout treatment to optimize response.
DEVICETranscranial Magnetic Stimulation Sham
Sham stimulation will be delivered using the same Neurocare Apollo TMS Therapy System as the active intervention, with identical treatment schedule (5 days per week for 6 weeks; 30 minutes per session). A sham coil identical in appearance to the active coil will be used, which does not generate a therapeutic magnetic field. To mimic the sensory experience of active treatment, the sham procedure will produce similar auditory clicking and will include a surface electrical stimulation (TENS) applied to the forehead to replicate scalp sensations and mild muscle contraction. This approach is designed to maintain blinding while delivering no active neuromodulatory effect.
Sponsors
Massachusetts General Hospital
United States Air Force Research Laboratory
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Masking description
In addition to the masked participants and care providers, the study statistician and collaborating investigators at the United States Air Force Research Laboratory (AFRL) will also remain blinded to treatment allocation. All data shared with these parties will be coded and de-identified, with treatment groups labeled in a manner that prevents identification of active versus sham conditions until completion of the primary analysis or unless unblinding is required for safety reasons.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Reserve or former member of the military (veteran status) * Age 18 years or older * Primary diagnosis of post-traumatic stress disorder (PTSD) confirmed by the - Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) * Post-Traumatic Stress Disorder Checklist for DSM-5 (PCL-5) score ≥ 33, indicating clinically significant PTSD symptoms * Proficient in English (spoken and written) to ensure understanding of study procedures and informed consent
Exclusion criteria
* History of open-skull traumatic brain injury * Clinically significant seizure disorder or history of manic episodes * Neurological conditions associated with increased risk (e.g., increased intracranial pressure, brain lesions, stroke, cerebral aneurysm) * Electroencephalogram (EEG) abnormalities suggesting elevated seizure risk * Repetitive transcranial magnetic stimulation (rTMS) within 3 months prior to screening * Current use of antipsychotic or anticonvulsant medications * Presence of intracranial implants or non-removable metal in or near the head (excluding the mouth) * Clinically significant or unstable medical conditions, including active suicidal ideation * Uncontrolled medical illness (e.g., thyroid, hepatic, cardiac, pulmonary, or renal disease) * Initiation of PTSD-specific treatment within the past 4 weeks (participants on a stable regimen may be eligible) * Pregnancy (for women of childbearing potential) * Any condition that, in the opinion of the investigator, may interfere with study participation or completion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) | At baseline and the end of treatment at Week 6. | The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) is a structured interview and gold standard for diagnosing and assessing PTSD in clinical and research settings. It assesses current or lifetime PTSD based on DSM-5 criteria and measures symptom severity across the 20 PTSD symptoms, including the dissociative subtype, in relation to a single index traumatic event. Total severity scores range from 0 to 80, with higher scores indicating worse PTSD symptom severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Post-Traumatic Stress Disorder Checklist for DSM-5 (PCL-5) | At baseline, and weekly during Weeks 1-6, and at Week 10, Week 22, and Week 34. | The Post-Traumatic Stress Disorder Checklist for DSM-5 (PCL-5) is a 20-item self-report measure that assesses PTSD symptom presence and severity across DSM-5 symptom clusters, including re-experiencing, avoidance, negative alterations in cognition and mood, and arousal. Total scores range from 0 to 80, with higher scores indicating greater PTSD symptom severity. |
| Generalized Anxiety Disorder-7 (GAD-7) | At baseline, and weekly during Weeks 1-6, and at Week 10, Week 22, and Week 34. | The Generalized Anxiety Disorder-7 (GAD-7) is a seven-item self-report scale used to assess the severity of generalized anxiety symptoms and to screen for anxiety over the past two weeks. Total scores range from 0 to 21, with higher scores indicating greater anxiety severity. |
| Patient Health Questionnaire-9 (PHQ-9) | At baseline, and weekly during Weeks 1-6, and at Week 10, Week 22, and Week 34. | The Patient Health Questionnaire-9 (PHQ-9) is a 9-item self-report measure used to screen, diagnose, monitor, and assess the severity of depression. Total scores range from 0 to 27, with higher scores indicating greater depression severity. |
| Tinnitus Functional Index (TFI) | At baseline, and weekly during Weeks 1-6, and at Week 10, Week 22, and Week 34. | The Tinnitus Functional Index (TFI) is a 25-item self-report questionnaire designed to measure the severity, negative impact, and treatment-related changes of tinnitus on a person's daily life over the past week. Total scores range from 0 to 100, with higher scores indicating greater tinnitus severity and functional impact. |
| TMS Tolerability Worksheet (TTW) | At baseline and weekly during Weeks 1-6. | The TMS Tolerability Worksheet (TTW) is a clinician-administered tool used to document session-related side effects and adverse events associated with transcranial magnetic stimulation (TMS), including symptoms such as headache, neck pain, discomfort at the stimulation site, and hearing changes, with severity categorized as none, mild, moderate, or severe. |
| Pittsburgh Sleep Quality Index Addendum (PSQI-A) | At baseline, and weekly during Weeks 1-6, and at Week 10, Week 22, and Week 34. | The Pittsburgh Sleep Quality Index Addendum for PTSD (PSQI-A) is a self-report measure that assesses disruptive nocturnal behaviors associated with PTSD, including nightmares, panic, hot flashes, and acting out dreams. Total scores range from 0 to 21, with higher scores indicating greater severity of disruptive nocturnal behaviors. |
| Total Sleep Time (Oura Ring) | Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34. | Total sleep time, measured in hours per night using the Oura Ring wearable device. |
| Sleep Efficiency (Oura Ring) | Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34. | Sleep efficiency, expressed as a percentage (0-100%) representing the ratio of time spent asleep relative to the total time in bed, using the Oura Ring wearable device. |
| Sleep Latency (Oura Ring) | Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34. | Sleep latency, measured in minutes, defined as the time from the start of the sleep period to sleep onset, as recorded by the Oura Ring wearable device. Typical values range from approximately 0 to 60 minutes. |
| REM Sleep Duration (Oura Ring) | Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34. | Duration of rapid eye movement (REM) sleep, measured in minutes using the Oura Ring wearable device. |
| REM Sleep Percentage (Oura Ring) | Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34. | REM sleep expressed as a percentage of total sleep time, measured using the Oura Ring wearable device. |
| Light Sleep Duration (Oura Ring) | Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34. | Duration of light sleep, measured in minutes using the Oura Ring wearable device. |
| Light Sleep Percentage (Oura Ring) | Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34. | Light sleep expressed as a percentage of total sleep time, measured using the Oura Ring wearable device. |
| Deep Sleep Duration (Oura Ring) | Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34. | Duration of deep (slow-wave) sleep, measured in minutes using the Oura Ring wearable device. |
| Deep Sleep Percentage (Oura Ring) | Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34. | Deep (slow-wave) sleep expressed as a percentage of total sleep time, measured using the Oura Ring wearable device. |
| Resting Heart Rate (Oura Ring) | Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34. | Resting heart rate, measured in beats per minute (bpm) using the Oura Ring wearable device. |
| Heart Rate Variability (Oura Ring) | Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34. | Heart rate variability (HRV), measured in milliseconds (ms) using the Oura Ring wearable device. |
| Body Temperature (Oura Ring) | Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34. | Nightly body temperature deviation from baseline, measured in degrees Fahrenheit (°F) using the Oura Ring wearable device. |
| Daily Step Count (Oura Ring) | Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34. | Daily step count, measured as the number of steps per day using the Oura Ring wearable device. |
| Active Energy Expenditure (Oura Ring) | Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34. | Active energy expenditure, measured in kilocalories per day (kcal/day) using the Oura Ring wearable device. |
| Total Energy Expenditure (Oura Ring) | Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34. | Total energy expenditure, measured in kilocalories per day (kcal/day) using the Oura Ring wearable device. |
| Sedentary Activity Duration (Oura Ring) | Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34. | Duration of sedentary activity, measured in minutes per day using the Oura Ring wearable device. |
| Light Activity Duration (Oura Ring) | Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34. | Duration of light physical activity, measured in minutes per day using the Oura Ring wearable device. |
| Moderate Activity Duration (Oura Ring) | Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34. | Duration of moderate physical activity, measured in minutes per day using the Oura Ring wearable device. |
| Vigorous Activity Duration (Oura Ring) | Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34. | Duration of vigorous physical activity, measured in minutes per day using the Oura Ring wearable device. |
Countries
United States
Contacts
CONTACTJoseph Bonvie, PsyD
CONTACTAlan Berkeley, MBA
PRINCIPAL_INVESTIGATORSofia E Matta, MD
Massachusetts General Hospital
Outcome results
None listed