Major Depressive Disorder, Posttraumatic Stress Disorder, Transcranial Magnetic Stimulation, Repetitive
Conditions
Keywords
PTSD, MDD, TMS, 5Hz
Brief summary
The purpose of this study is to see how well a treatment called Repetitive Transcranial Magnetic Stimulation works for patients who struggle with symptoms of both posttraumatic stress disorder and major depressive disorder.
Detailed description
This study aims to evaluate the safety and efficacy of repetitive transcranial magnetic stimulation (rTMS) for adults with comorbid posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). Although standard rTMS uses stimulations delivered to the left prefrontal cortex at 10 pulses per second, prior work has shown that other stimulation frequencies may work for both PTSD and MDD. In this study, we examine the efficacy of left-sided 5Hz in patients with PTSD and MDD, hypothesizing that this lower frequency will improve PTSD and MDD symptoms.
Interventions
DEVICETranscranial Magnetic Stimulation (TMS)
Up to 40 sessions of TMS delivered with the first 35 sessions delivered over 7 weeks, and final 5 treatments delivered in taper schedule over 3 weeks. Treatment is adjunct to ongoing stable pharmacotherapy.
Sponsors
Providence VA Medical Center
Neuronetics
Butler Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. To ensure subjects can safely receive rTMS, eligible subjects must meet all established screening criteria for safety during MRI (magnetic resonance imaging), since MRI involves magnetic fields at similar intensity to those emitted from the rTMS treatment coil. These are conservative measures require a patient not having the following (unless MRI-safe): Cardiac pacemaker, implanted device (deep brain stimulation) or metal in the brain, cervical spinal cord, or upper thoracic spinal cord; 2. Outpatients 18-70 years of age (inclusive) 3. Meet DSM-IV criteria for MDD (recurrent or single episode chronic) and PTSD (acute or chronic) at the time of the screening and baseline visits; 4. Have a baseline score of Moderately Ill or worse on both the CGI-S and the PGI-S. 5. Have failed at least one antidepressant medication trial as part of definitive and adequate treatment in the current episode, OR have demonstrated intolerance to at least one antidepressant medication as part of attempted treatment in the current episode of illness (i.e., meet FDA labeling requirements for administration of rTMS for depression); 6. Be on a stable psychotropic regimen for at least six weeks (42 days) prior to screening, or no psychotropic medication at all, and be willing to maintain the current regimen and dosing for the duration of the study (unless medical necessary to make changes with notification of research staff); 7. If female and of child bearing potential, agree to use an acceptable method of birth control for the duration of the study treatment period 8. Be willing and able to comply with all study related procedures and visits, 9. Be capable of independently reading and understanding patient information materials and giving written informed consent.
Exclusion criteria
1. Are pregnant or lactating or planning to become pregnant within the next three months. 2. Have a lifetime history of loss of consciousness due to head injury for greater than 10 minutes, or any lifetime history of loss of consciousness due to a head injury with documented evidence of brain injury (including brain atrophy). 3. Current (or past if appropriate) significant neurological disorder, or lifetime history of a) seizure disorder b) primary or secondary CNS tumors c) stroke or d) cerebral aneurysm; 4. Current Axis 1 primary psychotic disorder, or bipolar I disorder, current alcohol and/or substance dependence or abuse within the past 1 month; 5. Past treatment with TMS therapy 6. Have active suicidal intent or plan as detected on screening assessments, or in the Investigator's opinion, is likely to attempt suicide within the next six months. 7. Demonstrate the presence of any other condition or circumstance that, in the opinion of the investigator, has the potential to prevent study completion and/or to have a confounding effect on outcome assessments.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Score on PTSD Checklist for DSM-5 (PCL-5) | Baseline to final TMS session (up to 40 sessions over up to 8 weeks) | This self-report scale is called: PTSD Checklist for DSM-5 (abbreviated PCL-5) (see https://www.ptsd.va.gov/professional/assessment/adult-sr/ptsd-checklist.asp). Total PCL-5 score ranges from 0 to 80. Analysis of treatment effect on symptom severity will be evaluated by change in PCL-5 total score from baseline (pre-TMS) to endpoint (post-TMS)(or LOCF); Paired t-test compares the mean total PCL-score for the group at the two time points. A higher total score on the PCL-5 scale corresponds with more severe PTSD symptoms than a lower total score. A greater change from baseline to endpoint would correspond with better treatment outcome. |
| Total Score on Inventory of Depressive Symptomatology, Self-Report (IDS-SR) Scale | Baseline to final TMS session (up to 40 sessions over up to 8 weeks) | This self-report scale is called Inventory of Depressive Symptomatology, Self-Report (Abbreviated IDS-SR). IDS-SR Total Scores Range from 0 to 84, with a higher score reflecting greater depressive symptom severity. Paired t-test compares the change in mean total IDS-SR score from baseline (pre-TMS) to endpoint (last TMS session) or LOCF. A greater change reflects a better outcome than lesser change. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TMS Prescription 5Hz delivered over L DLPFC. Intensity: 120% of Motor Threshold, 5 Sec Train, 14 Sec Inter-Train Interval, Frequency: 5Hz, Total Pulses: 3000
Transcranial Magnetic Stimulation: Stimulating DLPFC at 5 Hz for up to 40 treatment sessions overall. 35 sessions delivered over 7 weeks, and final 5 treatments delivered in taper over 3 weeks. There will be a post treatment assessment 72 hours after final treatment, and then again 1 month after the final treatment. | 35 |
| Total | 35 |
Baseline characteristics
| Characteristic | TMS Prescription |
|---|---|
| Age, Continuous | 51.6 years STANDARD_DEVIATION 10.3 |
| Race/Ethnicity, Customized Black | 1 Participants |
| Race/Ethnicity, Customized Multiracial | 1 Participants |
| Race/Ethnicity, Customized White | 33 Participants |
| Region of Enrollment United States | 35 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 35 |
| serious Total, serious adverse events | 4 / 35 |
Outcome results
Primary
Total Score on Inventory of Depressive Symptomatology, Self-Report (IDS-SR) Scale
This self-report scale is called Inventory of Depressive Symptomatology, Self-Report (Abbreviated IDS-SR). IDS-SR Total Scores Range from 0 to 84, with a higher score reflecting greater depressive symptom severity. Paired t-test compares the change in mean total IDS-SR score from baseline (pre-TMS) to endpoint (last TMS session) or LOCF. A greater change reflects a better outcome than lesser change.
Time frame: Baseline to final TMS session (up to 40 sessions over up to 8 weeks)
Population: intent-to-treat population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Transcranial Magnetic Stimulation (TMS) | Total Score on Inventory of Depressive Symptomatology, Self-Report (IDS-SR) Scale | BASELINE | 47.8 units on a scale | Standard Deviation 11.9 |
| Transcranial Magnetic Stimulation (TMS) | Total Score on Inventory of Depressive Symptomatology, Self-Report (IDS-SR) Scale | ENDPOINT | 30.9 units on a scale | Standard Deviation 18.9 |
Primary
Total Score on PTSD Checklist for DSM-5 (PCL-5)
This self-report scale is called: PTSD Checklist for DSM-5 (abbreviated PCL-5) (see https://www.ptsd.va.gov/professional/assessment/adult-sr/ptsd-checklist.asp). Total PCL-5 score ranges from 0 to 80. Analysis of treatment effect on symptom severity will be evaluated by change in PCL-5 total score from baseline (pre-TMS) to endpoint (post-TMS)(or LOCF); Paired t-test compares the mean total PCL-score for the group at the two time points. A higher total score on the PCL-5 scale corresponds with more severe PTSD symptoms than a lower total score. A greater change from baseline to endpoint would correspond with better treatment outcome.
Time frame: Baseline to final TMS session (up to 40 sessions over up to 8 weeks)
Population: intent-to-treat population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Transcranial Magnetic Stimulation (TMS) | Total Score on PTSD Checklist for DSM-5 (PCL-5) | BASELINE | 52.2 units on a scale | Standard Deviation 13.1 |
| Transcranial Magnetic Stimulation (TMS) | Total Score on PTSD Checklist for DSM-5 (PCL-5) | ENDPOINT | 34.0 units on a scale | Standard Deviation 21.6 |