TBI Depression
Conditions
Keywords
TBI Depression, co-morbid psychiatric symptoms
Brief summary
Traumatic brain injury (TBI) is frequently complicated by depression and other problems such as post traumatic stress disorder (PTSD), sleep disturbance, cognitive deficits and behavioral problems. Untreated depression can lead to reduced productivity and poor global outcome. There is no Food and Drug Administration (FDA) approved drug for the treatment of TBI-related depression. The overarching goal of this small study is to determine the effectiveness of low frequency right (LFR) rTMS for the treatment of post-TBI depression and co-occurring psychiatric symptoms. Repetitive transcranial magnetic stimulation (rTMS) is a brain stimulation technique. It involves generating a brief magnetic field in a coil that is placed on the scalp. The magnetic field passes through the skull and induces a weak electrical current in the brain that briefly activates neural circuits at the stimulation site. Adults aged 18 and older, with a history of head injury of mild or moderate severity , who are currently experiencing symptoms of clinical depression may join the study.
Interventions
COMBINATION_PRODUCTLow Frequency Right sided repetitive transcranial magnetic stimulation (LFR rTMS)
LFR rTMS will be delivered at the Brain Stimulation Program at The Johns Hopkins Hospital with a Magstim Super Rapid 2 stimulator with a focal double 70-mm air cooled coil. LFR rTMS will be administered to the Experimental Group. Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength.
DEVICESham Comparator: Sham Treatment
Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength
Sponsors
United States Department of Defense
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Adults aged 18 and over 2. H/o closed head injury 3. Must meet Department of Defense (DoD) criteria for mild or moderate Traumatic Brain Injury (TBI) 4. Must meet criteria for major depression as assessed by the Structured Clinical Interview (SCID) for Diagnostic and Statistical Manual IV (DSM-IV) and a score greater than 10 on the Hamilton Depression 17 (HAM-D17) Scale
Exclusion criteria
1. Subjects with skull fracture 2. Subjects who meet DoD criteria for severe TBI 3. Subjects who are on psychotropics or mood stabilizing medications (e.g. antidepressants, antipsychotics, anxiolytics, sedative/hypnotics. 4. Subjects who are medically unstable 5. History of active substance abuse x 1 month 6. Current psychotic illness 7. Evidence of frontal lesions on brain scan. 8. Individuals with a significant neurological disorders that could increase risk of seizures such as brain tumor, cerebral aneurysm, any h/o seizures and/or family h/o seizures 9. Dementia 10. Mini Mental State Exam score of less than or equal to 24 11. A positive and unmitigated response to any question on the Transcranial Magnetic Stimulation Safety Screen questionnaire 12. Electroconvulsive therapy (ECT) treatment within 6 months prior to the screening visit 13. History of treatment with rTMS therapy for any disorder 14. History of treatment with Vagus Nerve Stimulation (VNS) 15. History of treatment with Deep Brain Stimulation (DBS) 16. Cardiac pacemakers, implanted medication pumps, intracardiac lines, 17. Intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed. 18. Implanted neurostimulators 19. Known or suspected pregnancy 20. Investigators, personnel affiliated with this study, and their immediate families.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Depression Score Using the Hamilton Depression (HAM-D) 17 Scale | Mean at baseline, 4 weeks, 8 weeks, 12 weeks, and 16 weeks | The HAM-D was used to determine the effectiveness of LFR rTMS for the treatment of post-TBI depression. The scale ranges from 0-54, with 0-7 = Normal; 8-13= Mild Depression; 14-18= Moderate Depression, 19-22= Severe Depression, \>/= 23 = Very Severe Depression. |
| Mean Clinical Global Improvement- Severity/Improvement Scale Score (CGI-I/CGI-S) | Mean at baseline, 4, 8, 12, and 16 weeks | The CGI scale is broken down into the CGI-S and CGI-I components. CGI-S is the baseline severity of mental illness. 1= normal, not at all ill; 2= borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients. The CGI-S is only performed at baseline. The CGI-I component (which is any measure after intervention) is as follows: 1=very much improved since the initiation of treatment; 2=much improved; 3=minimally improved; 4=no change from baseline (the initiation of treatment); 5=minimally worse; 6= much worse; 7=very much worse since the initiation of treatment. |
| Mean Suicidal Ideation as Assessed by the Beck Suicidal Ideation Scale (BSSI) | Mean at baseline, 4, 8, 12, and 16 weeks | The BSSI scale is used to assess the degree of suicidal ideation. The scale ranges from 0-38, with 0= no suicidality, and 38 = highest severity of suicidal ideation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cognitive Reasoning as Assessed by the Number of Correct Trials on the Wisconsin Card Scoring Test (WCST) | Mean at baseline and 16 weeks | The participant points to choice on the screen and the tester manipulates the mouse to make the response. The participant tells the tester if he or she wants to change the response and the tester clicks on the screen. The score is the number of correct trials, ranging from 0-128. A higher score reflects a better outcome. |
| Evaluation of Brain Injury as Assessed by the Trailmaking Test B Score | Mean at baseline and 16 weeks | The Trailmaking B score is the number of seconds spent connecting numbered circles (1-13) to circles containing letters of the alphabet (A-L) in alternating sequential order. A maximum of 300 seconds is allowed. Score ranges from 0-300. Higher score reflects poorer outcome. |
| Immediate Recall as Assessed by Hopkins Verbal Learning Test (HVLT) | Mean at baseline and 16 weeks | The Hopkins Verbal Learning Test (HVLT) consists of a 12-item word list, composed of four words from each of the three semantic categories. The subject is instructed to listen carefully as the examiner reads the word list and attempt to memorize the words. The word list is then read to the subject at the approximate rate of one word every 2 seconds. This is done for three trials. The number of correctly-recalled words in each trial is recorded (maximum of 12). The score is a sum of all the correctly-recalled words from each trial, for a maximum score of 36. |
| Delayed Recall as Assessed by Hopkins Verbal Learning Test (HVLT) | Mean at baseline and 16 weeks | The HVLT consists of a 12-item word list, composed of four words from each of the three semantic categories. The subject is instructed to listen carefully as the examiner reads the word list and attempt to memorize the words. The word list is then read to the subject at the approximate rate of one word every 2 seconds. This is done for three trials. After the third learning trial, the patient is read 24 words and is asked to say yes after each word that appeared on the recall list (12 targets) and no after each word that did not (12 distractors). Half of the distractors are drawn from the same semantic categories as the targets (related distractors) and half are drawn from other categories (unrelated distractors). The number of correctly-recalled words in each trial is recorded (maximum of 12 per trial). The score is the sum of all the correctly-recalled words from each trial, for a maximum of 36. T-scores are reported (average T-score of 50 (ranges 40-60) |
| Delayed Recall as Assessed by Brief Visual Memory Test (BVMT) | Mean at baseline and 16 weeks | BVMT is used to evaluate visuospatial memory abilities in neuropsychological populations. A visual display of six simple figures arranged in a 2 × 3 matrix on an 8 × 11 booklet is shown to participants for three consecutive 10-second trials. After each trial, participants are to draw as many designs as accurately as they can and in the correct location after a 25-minute delay filled with other distractor tasks. Scoring of the delayed recall is based on the accuracy of the drawings and the location of the figures. For each figure, one point is awarded to each satisfactory domain resulting in a maximum of 12-points per trial for a total score range of 0-36, with higher scores indicating a better outcome. |
| Immediate Recall as Assessed by Brief Visual Memory Test (BVMT) | Mean at baseline and 16 weeks | BVMT is used to evaluate visuospatial memory abilities in neuropsychological populations. A visual display of six simple figures arranged in a 2 × 3 matrix on an 8 × 11 booklet is shown to participants for three consecutive 10-second trials. After each trial, participants are to draw as many designs as accurately as they can and in the correct location. Scoring of the immediate recall is based on the accuracy of the drawings and the location of the figures. For each figure, one point is awarded to each satisfactory domain resulting in a maximum of 12-points per trial, for a total score ranging from 0-36, with a higher score reflecting a better outcome. |
| Evaluation of Brain Injury as Assessed by the Trailmaking Test A Score | Mean at baseline and 16 weeks | Trailmaking A is a psychological test with a score that is the number of seconds spent in connecting 25 numbered circles in sequential order. Score ranges from 0-150. Higher score reflects poorer outcome. |
| Mean Generalized Anxiety Disorder (GAD) - 7 Questionnaire | Baseline, 4, 8, 12, and 16 weeks | The GAD-7 questionnaire is used as a screening tool and severity measure for generalized anxiety disorder. The scale ranges from 0 - 21. 0-4 = normal 5-9 = mild 10-14 = moderate \>15 = severe |
| Mean Trauma Severity as Assessed by the Davidson Trauma Scale (DTS) | Baseline, 4, 8, 12, and 16 weeks | The DTS is a 17-item self-reported measure that assesses the 17 Diagnostic and Statistical Manual IV (DSM-IV) symptoms of post-traumatic stress disorder (PTSD). Items are rated on 5-point frequency (0 = not at all to 4 = every day) and severity scales (0 = not at all distressing to 4 = extremely distressing). The DTS yields a frequency score (ranging from 0 to 68), severity score (ranging from 0 to 68), and total score (ranging from 0 to 136). The severity score will be used to assess this outcome. |
| Ability to Inhibit Cognitive Interference as Assessed by the Stroop Color Word Test (SCWT) | Mean at baseline and 16 weeks | The SCWT is used to assess the ability to inhibit cognitive interference that occurs when the processing of a specific stimulus feature impedes the simultaneous processing of a second stimulus attribute. Participants are required to read three different tables as fast as possible. Two of the tables represent the congruous condition in which participants are required to read names of colors printed in black ink and name different color patches. In the third table, incongruous condition the color-words are printed in a different color in (ie: the word red is printed in green ink). Within this third table, participants are required to name the color of the ink instead of reading the word. The score is based on the number of items completed, which ranges from 0 to 100, with a higher score reflecting a better outcome. |
| Mean Level of Fatigue as Assessed by the Epworth Sleepiness Scale (ESS) | Baseline, 4, 8, 12, and 16 weeks | The ESS is used to determine the level of daytime sleepiness. It is a questionnaire composed of 8 questions. The participant answers each question on a scale of 0 to 3 (0=no sleepiness, 1= mild sleepiness, 2= moderate sleepiness, 3= severe sleepiness). The total score is the sum of all responses for a maximum score of 24. A higher score reflects increased sleepiness. |
| Mean Cognitive Function as Assessed by the Montreal Cognitive Assessment (MOCA) | Mean at baseline and 16 weeks | MOCA is designed to assess cognitive impairment and Alzheimer's Disease. It is composed of the following: Visuospatial and Executive Functioning: 5 points Animal Naming: 3 points Attention: 6 points Language: 3 points Abstraction: 2 points Delayed Recall (Short-term Memory): 5 points Orientation: 6 points Education Level: 1 point is added to the test-taker's score if he or she has 12 years or less of formal education. Score ranges 0-31, with ≥ 26 being normal cognitive function. The lower the score, the greater the level of cognitive impairment. |
| Presence of Neuropsychiatric Symptoms as Assessed by Neurobehavioral Rating Scale (NBRS) | Mean at baseline, 4, 8, 12, and 16 weeks | The NBRS is a 28-item interview which includes a test of orientation and memory for recent events, questions regarding emotional state, post-concussional symptoms, focused attention, and concentration (performing serial sevens), explanation of proverbs, tasks of planning and mental flexibility, and delayed recall of three objects presented at the beginning of a session. Observations are also made regarding the patient's fatigability, visible signs of anxiety, disinhibition, agitation, hostility, difficulties in expressive and receptive communication, and disturbance of mood. The balance of the items are rated according to the patient's performance on brief tasks and quality of answers to interview questions. Each of the 28 items are scored on a scale of 0 (not severe) to 6 (extremely severe), for a maximum score of 168. A higher score reflects increased severity of neuropsychiatric symptoms. |
| Presence of Post-concussive Symptoms as Assessed by the Rivermead Post-Concussion Questionnaire (RPQ) | Mean at baseline, 4, 8, 12, and 16 weeks | Participants are asked to rate the severity of 16 different symptoms over the past 24 hours, on a severity scale from 0 to 4 (0 = not experienced, 1 = no more of a problem, 2 = mild problem, 3 = moderate problem, 4 = severe problem). The 16 symptoms include: headaches, dizziness, nausea and/or vomiting, hyperacusis, sleep disturbance, fatigue, being irritable, feeling depressed, feeling frustrated, forgetfulness, poor concentration, taking longer to think, blurred vision, light sensitivity, double vision, restlessness. Score ranges from 0 to 64, with a higher score reflecting increased severity of post-concussive symptoms. |
| Fatigue Severity as Assessed by the Fatigue Severity Scale (FSS) | Mean at baseline, 4, 8, 12, and 16 weeks | The FSS is a 9-item questionnaire which measures the severity of fatigue and how it interferes with certain activities. The items are scored on a 7-point scale with 1=strongly disagree and 7=strongly agree. The score ranges from 9 to a maximum of 63. A higher score reflects greater fatigue severity. |
| Aggressive Behavior as Assessed by the Modified Overt Aggression Scale (MOAS) | Mean at baseline, 4, 8, 12, and 16 weeks | MOAS measures four types of aggressive behavior as witnessed in the past week. Each section consists of five items, with the first section regarding verbal aggression, the second section focusing on aggression against property, the third section measuring autoaggression, and the fourth section concerning physical aggression. Participants are asked to check each item that is true over the last week. Items are allocated 0, 1, 2, 3 or 4 point(s), and then all points for each selected item are summed. The maximum total for each section is 10 if all items are selected. Total score ranges from 0-40 with a higher score indicating more aggressive behavior. |
| Overall Satisfaction With Life as Assessed by the Satisfaction With Life (SWL) Questionnaire | Mean at baseline, 4, 8, 12, and 16 weeks | The SWL is a 7-point Likert-style response scale. The possible range of scores is 5-35, with a score of 20 representing a neutral point on the scale. Scores between 5-9 indicate the respondent is extremely dissatisfied with life, whereas scores between 31-35 indicate the respondent is extremely satisfied. |
| Presence of Social Connections as Assessed by the Social Ties Checklist (STC) | Mean at baseline, 4, 8, 12, and 16 weeks | The STC reflects the level of social contact. The score ranges from 0-10, with 0= excellent contact, 10=no contact. A higher score reflects poorer social contact. |
| Mean Level of Fatigue as Assessed by Patient Sleep Quality Index (PSQI) | Baseline, 4, 8, 12, and 16 weeks | The PSQI score scale ranges from 0-21. 0 = very good sleep quality 21 = very bad sleep quality A total score of 5 or greater is indicative of poor sleep quality (reflecting a higher level of fatigue) |
| Cognitive Reasoning as Assessed by the Number of Completed Categories on the Wisconsin Card Scoring Test (WCST) | Mean at baseline and 16 weeks | The participant points to choice on the screen and the tester manipulates the mouse to make the response. The participant tells the tester if he or she wants to change the response and the tester clicks on the screen. The score is the number of completed categories, ranging from 0-6. A higher score reflects a better outcome. |
| Cognitive Reasoning as Assessed by the Number of Errors Made on the Wisconsin Card Sorting Test (WCST) | Mean at baseline and 16 weeks | The participant points to choice on the screen and the tester manipulates the mouse to make the response. The participant tells the tester if he or she wants to change the response and the tester clicks on the screen. The score is the number of errors, ranging from 0-128. A higher score reflects a poorer outcome. |
Countries
United States
Participant flow
Recruitment details
70 participants passed screening & were enrolled in study. 36 were not randomized.14 lost to follow-up, 5 refused due to scheduling, 5 did not meet DSM IV criteria: major depression, 3 concerns about receiving rTMS, 2 psychotropics, 2 did not have TBI, 1 using illicit drugs, 1 skull fracture, 1 severe TBI, 1 with seizure history, 1 MRI focal lesion
Participants by arm
| Arm | Count |
|---|---|
| Sham Treatment Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength
Sham Comparator: Sham Treatment: Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength | 17 |
| LFR rTMS Investigators propose to deliver 1200 pulses daily at 110% Motor threshold for 4 weeks using four trains of 300 pulses daily separated by an intertrain interval of 60 seconds.
Low Frequency Right sided repetitive transcranial magnetic stimulation (LFR rTMS): LFR rTMS will be delivered at the Brain Stimulation Program at The Johns Hopkins Hospital with a Magstim Super Rapid 2 stimulator with a focal double 70-mm air cooled coil. LFR rTMS will be administered to the Experimental Group.
Control patients will receive treatment using an identically appearing coil that produces the same sound and is the same weight as the active coil, but has negligible magnetic field strength. | 13 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | severe headache after intervention | 2 | 0 |
| Overall Study | unable to find transportation | 2 | 0 |
Baseline characteristics
| Characteristic | Sham Treatment | LFR rTMS | Total |
|---|---|---|---|
| Age, Continuous | 40.2 years STANDARD_DEVIATION 14.6 | 39.8 years STANDARD_DEVIATION 14.2 | 40 years STANDARD_DEVIATION 14.4 |
| Months Depressed Since Injury | 39.4 months STANDARD_DEVIATION 43 | 39.6 months STANDARD_DEVIATION 36.1 | 39.47 months STANDARD_DEVIATION 39.51 |
| Race/Ethnicity, Customized Non-White | 7 Participants | 4 Participants | 11 Participants |
| Race/Ethnicity, Customized White | 10 Participants | 9 Participants | 19 Participants |
| Region of Enrollment United States | 17 Participants | 13 Participants | 30 Participants |
| Sex: Female, Male Female | 6 Participants | 8 Participants | 14 Participants |
| Sex: Female, Male Male | 11 Participants | 5 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 17 |
| other Total, other adverse events | 6 / 17 | 7 / 17 |
| serious Total, serious adverse events | 0 / 17 | 0 / 17 |
Outcome results
Primary
Average Depression Score Using the Hamilton Depression (HAM-D) 17 Scale
The HAM-D was used to determine the effectiveness of LFR rTMS for the treatment of post-TBI depression. The scale ranges from 0-54, with 0-7 = Normal; 8-13= Mild Depression; 14-18= Moderate Depression, 19-22= Severe Depression, \>/= 23 = Very Severe Depression.
Time frame: Mean at baseline, 4 weeks, 8 weeks, 12 weeks, and 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LFR rTMS | Average Depression Score Using the Hamilton Depression (HAM-D) 17 Scale | 4 weeks | 13.154 units on a scale | Standard Deviation 8.444 |
| LFR rTMS | Average Depression Score Using the Hamilton Depression (HAM-D) 17 Scale | 12 weeks | 14.077 units on a scale | Standard Deviation 10.21 |
| LFR rTMS | Average Depression Score Using the Hamilton Depression (HAM-D) 17 Scale | 8 weeks | 12.538 units on a scale | Standard Deviation 9.744 |
| LFR rTMS | Average Depression Score Using the Hamilton Depression (HAM-D) 17 Scale | 16 weeks | 11.154 units on a scale | Standard Deviation 9.529 |
| LFR rTMS | Average Depression Score Using the Hamilton Depression (HAM-D) 17 Scale | Baseline | 23.154 units on a scale | Standard Deviation 4.375 |
| Sham Treatment | Average Depression Score Using the Hamilton Depression (HAM-D) 17 Scale | 16 weeks | 12.941 units on a scale | Standard Deviation 8.877 |
| Sham Treatment | Average Depression Score Using the Hamilton Depression (HAM-D) 17 Scale | Baseline | 23.076 units on a scale | Standard Deviation 4.356 |
| Sham Treatment | Average Depression Score Using the Hamilton Depression (HAM-D) 17 Scale | 4 weeks | 12.706 units on a scale | Standard Deviation 6.697 |
| Sham Treatment | Average Depression Score Using the Hamilton Depression (HAM-D) 17 Scale | 8 weeks | 12.647 units on a scale | Standard Deviation 6.901 |
| Sham Treatment | Average Depression Score Using the Hamilton Depression (HAM-D) 17 Scale | 12 weeks | 12.824 units on a scale | Standard Deviation 8.435 |
Primary
Mean Clinical Global Improvement- Severity/Improvement Scale Score (CGI-I/CGI-S)
The CGI scale is broken down into the CGI-S and CGI-I components. CGI-S is the baseline severity of mental illness. 1= normal, not at all ill; 2= borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients. The CGI-S is only performed at baseline. The CGI-I component (which is any measure after intervention) is as follows: 1=very much improved since the initiation of treatment; 2=much improved; 3=minimally improved; 4=no change from baseline (the initiation of treatment); 5=minimally worse; 6= much worse; 7=very much worse since the initiation of treatment.
Time frame: Mean at baseline, 4, 8, 12, and 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LFR rTMS | Mean Clinical Global Improvement- Severity/Improvement Scale Score (CGI-I/CGI-S) | CGI 4 weeks (improvement) | 2.308 units on a scale | Standard Deviation 1.109 |
| LFR rTMS | Mean Clinical Global Improvement- Severity/Improvement Scale Score (CGI-I/CGI-S) | CGI 12 weeks (improvement) | 2.385 units on a scale | Standard Deviation 1.0444 |
| LFR rTMS | Mean Clinical Global Improvement- Severity/Improvement Scale Score (CGI-I/CGI-S) | CGI 8 weeks (improvement) | 2.385 units on a scale | Standard Deviation 1.044 |
| LFR rTMS | Mean Clinical Global Improvement- Severity/Improvement Scale Score (CGI-I/CGI-S) | CGI 16 weeks (improvement) | 2.077 units on a scale | Standard Deviation 0.854 |
| LFR rTMS | Mean Clinical Global Improvement- Severity/Improvement Scale Score (CGI-I/CGI-S) | CGI Baseline (severity) | 4.846 units on a scale | Standard Deviation 0.801 |
| Sham Treatment | Mean Clinical Global Improvement- Severity/Improvement Scale Score (CGI-I/CGI-S) | CGI 16 weeks (improvement) | 2.471 units on a scale | Standard Deviation 1.281 |
| Sham Treatment | Mean Clinical Global Improvement- Severity/Improvement Scale Score (CGI-I/CGI-S) | CGI Baseline (severity) | 5 units on a scale | Standard Deviation 0.791 |
| Sham Treatment | Mean Clinical Global Improvement- Severity/Improvement Scale Score (CGI-I/CGI-S) | CGI 4 weeks (improvement) | 2.824 units on a scale | Standard Deviation 1.334 |
| Sham Treatment | Mean Clinical Global Improvement- Severity/Improvement Scale Score (CGI-I/CGI-S) | CGI 8 weeks (improvement) | 2.471 units on a scale | Standard Deviation 1.125 |
| Sham Treatment | Mean Clinical Global Improvement- Severity/Improvement Scale Score (CGI-I/CGI-S) | CGI 12 weeks (improvement) | 2.588 units on a scale | Standard Deviation 1.064 |
Primary
Mean Suicidal Ideation as Assessed by the Beck Suicidal Ideation Scale (BSSI)
The BSSI scale is used to assess the degree of suicidal ideation. The scale ranges from 0-38, with 0= no suicidality, and 38 = highest severity of suicidal ideation
Time frame: Mean at baseline, 4, 8, 12, and 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LFR rTMS | Mean Suicidal Ideation as Assessed by the Beck Suicidal Ideation Scale (BSSI) | Baseline | 0.462 units on a scale | Standard Deviation 1.127 |
| LFR rTMS | Mean Suicidal Ideation as Assessed by the Beck Suicidal Ideation Scale (BSSI) | 12 weeks | 0 units on a scale | Standard Deviation 0 |
| LFR rTMS | Mean Suicidal Ideation as Assessed by the Beck Suicidal Ideation Scale (BSSI) | 4 weeks | 0.077 units on a scale | Standard Deviation 0.277 |
| LFR rTMS | Mean Suicidal Ideation as Assessed by the Beck Suicidal Ideation Scale (BSSI) | 16 weeks | 0.00 units on a scale | Standard Deviation 0 |
| LFR rTMS | Mean Suicidal Ideation as Assessed by the Beck Suicidal Ideation Scale (BSSI) | 8 weeks | 0.154 units on a scale | Standard Deviation 0.376 |
| Sham Treatment | Mean Suicidal Ideation as Assessed by the Beck Suicidal Ideation Scale (BSSI) | 16 weeks | 0.471 units on a scale | Standard Deviation 0.943 |
| Sham Treatment | Mean Suicidal Ideation as Assessed by the Beck Suicidal Ideation Scale (BSSI) | 4 weeks | 0.706 units on a scale | Standard Deviation 1.359 |
| Sham Treatment | Mean Suicidal Ideation as Assessed by the Beck Suicidal Ideation Scale (BSSI) | 8 weeks | 0.353 units on a scale | Standard Deviation 0.862 |
| Sham Treatment | Mean Suicidal Ideation as Assessed by the Beck Suicidal Ideation Scale (BSSI) | 12 weeks | 0.529 units on a scale | Standard Deviation 1.007 |
| Sham Treatment | Mean Suicidal Ideation as Assessed by the Beck Suicidal Ideation Scale (BSSI) | Baseline | 1.294 units on a scale | Standard Deviation 1.896 |
Secondary
Ability to Inhibit Cognitive Interference as Assessed by the Stroop Color Word Test (SCWT)
The SCWT is used to assess the ability to inhibit cognitive interference that occurs when the processing of a specific stimulus feature impedes the simultaneous processing of a second stimulus attribute. Participants are required to read three different tables as fast as possible. Two of the tables represent the congruous condition in which participants are required to read names of colors printed in black ink and name different color patches. In the third table, incongruous condition the color-words are printed in a different color in (ie: the word red is printed in green ink). Within this third table, participants are required to name the color of the ink instead of reading the word. The score is based on the number of items completed, which ranges from 0 to 100, with a higher score reflecting a better outcome.
Time frame: Mean at baseline and 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LFR rTMS | Ability to Inhibit Cognitive Interference as Assessed by the Stroop Color Word Test (SCWT) | 0 weeks | 43.2 items completed | Standard Deviation 13.3 |
| LFR rTMS | Ability to Inhibit Cognitive Interference as Assessed by the Stroop Color Word Test (SCWT) | 16 weeks | 45.4 items completed | Standard Deviation 11.9 |
| Sham Treatment | Ability to Inhibit Cognitive Interference as Assessed by the Stroop Color Word Test (SCWT) | 0 weeks | 42.4 items completed | Standard Deviation 8.2 |
| Sham Treatment | Ability to Inhibit Cognitive Interference as Assessed by the Stroop Color Word Test (SCWT) | 16 weeks | 43.1 items completed | Standard Deviation 11.6 |
Secondary
Aggressive Behavior as Assessed by the Modified Overt Aggression Scale (MOAS)
MOAS measures four types of aggressive behavior as witnessed in the past week. Each section consists of five items, with the first section regarding verbal aggression, the second section focusing on aggression against property, the third section measuring autoaggression, and the fourth section concerning physical aggression. Participants are asked to check each item that is true over the last week. Items are allocated 0, 1, 2, 3 or 4 point(s), and then all points for each selected item are summed. The maximum total for each section is 10 if all items are selected. Total score ranges from 0-40 with a higher score indicating more aggressive behavior.
Time frame: Mean at baseline, 4, 8, 12, and 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LFR rTMS | Aggressive Behavior as Assessed by the Modified Overt Aggression Scale (MOAS) | 4 weeks | 1.308 units on a scale | Standard Deviation 1.377 |
| LFR rTMS | Aggressive Behavior as Assessed by the Modified Overt Aggression Scale (MOAS) | 12 weeks | 1.417 units on a scale | Standard Deviation 2.429 |
| LFR rTMS | Aggressive Behavior as Assessed by the Modified Overt Aggression Scale (MOAS) | 8 weeks | 0.692 units on a scale | Standard Deviation 0.855 |
| LFR rTMS | Aggressive Behavior as Assessed by the Modified Overt Aggression Scale (MOAS) | 16 weeks | 1.308 units on a scale | Standard Deviation 2.213 |
| LFR rTMS | Aggressive Behavior as Assessed by the Modified Overt Aggression Scale (MOAS) | Baseline | 2.308 units on a scale | Standard Deviation 2.136 |
| Sham Treatment | Aggressive Behavior as Assessed by the Modified Overt Aggression Scale (MOAS) | 16 weeks | 0.706 units on a scale | Standard Deviation 1.312 |
| Sham Treatment | Aggressive Behavior as Assessed by the Modified Overt Aggression Scale (MOAS) | Baseline | 3 units on a scale | Standard Deviation 4.016 |
| Sham Treatment | Aggressive Behavior as Assessed by the Modified Overt Aggression Scale (MOAS) | 4 weeks | 1.118 units on a scale | Standard Deviation 2.759 |
| Sham Treatment | Aggressive Behavior as Assessed by the Modified Overt Aggression Scale (MOAS) | 8 weeks | 0.471 units on a scale | Standard Deviation 1.068 |
| Sham Treatment | Aggressive Behavior as Assessed by the Modified Overt Aggression Scale (MOAS) | 12 weeks | 1 units on a scale | Standard Deviation 1.932 |
Secondary
Cognitive Reasoning as Assessed by the Number of Completed Categories on the Wisconsin Card Scoring Test (WCST)
The participant points to choice on the screen and the tester manipulates the mouse to make the response. The participant tells the tester if he or she wants to change the response and the tester clicks on the screen. The score is the number of completed categories, ranging from 0-6. A higher score reflects a better outcome.
Time frame: Mean at baseline and 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LFR rTMS | Cognitive Reasoning as Assessed by the Number of Completed Categories on the Wisconsin Card Scoring Test (WCST) | 0 weeks | 5.5 completed categories | Standard Deviation 0.707 |
| LFR rTMS | Cognitive Reasoning as Assessed by the Number of Completed Categories on the Wisconsin Card Scoring Test (WCST) | 16 weeks | 6 completed categories | Standard Deviation 0 |
| Sham Treatment | Cognitive Reasoning as Assessed by the Number of Completed Categories on the Wisconsin Card Scoring Test (WCST) | 0 weeks | 6 completed categories | Standard Deviation 0 |
| Sham Treatment | Cognitive Reasoning as Assessed by the Number of Completed Categories on the Wisconsin Card Scoring Test (WCST) | 16 weeks | 6 completed categories | Standard Deviation 0 |
Secondary
Cognitive Reasoning as Assessed by the Number of Correct Trials on the Wisconsin Card Scoring Test (WCST)
The participant points to choice on the screen and the tester manipulates the mouse to make the response. The participant tells the tester if he or she wants to change the response and the tester clicks on the screen. The score is the number of correct trials, ranging from 0-128. A higher score reflects a better outcome.
Time frame: Mean at baseline and 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LFR rTMS | Cognitive Reasoning as Assessed by the Number of Correct Trials on the Wisconsin Card Scoring Test (WCST) | Baseline | 74.5 correct trials | Standard Deviation 14.849 |
| LFR rTMS | Cognitive Reasoning as Assessed by the Number of Correct Trials on the Wisconsin Card Scoring Test (WCST) | 16 weeks | 67 correct trials | Standard Deviation 4.05 |
| Sham Treatment | Cognitive Reasoning as Assessed by the Number of Correct Trials on the Wisconsin Card Scoring Test (WCST) | Baseline | 68.857 correct trials | Standard Deviation 9.703 |
| Sham Treatment | Cognitive Reasoning as Assessed by the Number of Correct Trials on the Wisconsin Card Scoring Test (WCST) | 16 weeks | 69.667 correct trials | Standard Deviation 8.981 |
Secondary
Cognitive Reasoning as Assessed by the Number of Errors Made on the Wisconsin Card Sorting Test (WCST)
The participant points to choice on the screen and the tester manipulates the mouse to make the response. The participant tells the tester if he or she wants to change the response and the tester clicks on the screen. The score is the number of errors, ranging from 0-128. A higher score reflects a poorer outcome.
Time frame: Mean at baseline and 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LFR rTMS | Cognitive Reasoning as Assessed by the Number of Errors Made on the Wisconsin Card Sorting Test (WCST) | Baseline | 26 errors | Standard Deviation 24.042 |
| LFR rTMS | Cognitive Reasoning as Assessed by the Number of Errors Made on the Wisconsin Card Sorting Test (WCST) | 16 weeks | 10.5 errors | Standard Deviation 2.881 |
| Sham Treatment | Cognitive Reasoning as Assessed by the Number of Errors Made on the Wisconsin Card Sorting Test (WCST) | Baseline | 11 errors | Standard Deviation 5.354 |
| Sham Treatment | Cognitive Reasoning as Assessed by the Number of Errors Made on the Wisconsin Card Sorting Test (WCST) | 16 weeks | 8.667 errors | Standard Deviation 1.633 |
Secondary
Delayed Recall as Assessed by Brief Visual Memory Test (BVMT)
BVMT is used to evaluate visuospatial memory abilities in neuropsychological populations. A visual display of six simple figures arranged in a 2 × 3 matrix on an 8 × 11 booklet is shown to participants for three consecutive 10-second trials. After each trial, participants are to draw as many designs as accurately as they can and in the correct location after a 25-minute delay filled with other distractor tasks. Scoring of the delayed recall is based on the accuracy of the drawings and the location of the figures. For each figure, one point is awarded to each satisfactory domain resulting in a maximum of 12-points per trial for a total score range of 0-36, with higher scores indicating a better outcome.
Time frame: Mean at baseline and 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LFR rTMS | Delayed Recall as Assessed by Brief Visual Memory Test (BVMT) | Baseline | 9.23 accurately-drawn figures | Standard Deviation 2.713 |
| LFR rTMS | Delayed Recall as Assessed by Brief Visual Memory Test (BVMT) | 16 weeks | 8.308 accurately-drawn figures | Standard Deviation 3.066 |
| Sham Treatment | Delayed Recall as Assessed by Brief Visual Memory Test (BVMT) | Baseline | 9.688 accurately-drawn figures | Standard Deviation 3.005 |
| Sham Treatment | Delayed Recall as Assessed by Brief Visual Memory Test (BVMT) | 16 weeks | 8.813 accurately-drawn figures | Standard Deviation 2.509 |
Secondary
Delayed Recall as Assessed by Hopkins Verbal Learning Test (HVLT)
The HVLT consists of a 12-item word list, composed of four words from each of the three semantic categories. The subject is instructed to listen carefully as the examiner reads the word list and attempt to memorize the words. The word list is then read to the subject at the approximate rate of one word every 2 seconds. This is done for three trials. After the third learning trial, the patient is read 24 words and is asked to say yes after each word that appeared on the recall list (12 targets) and no after each word that did not (12 distractors). Half of the distractors are drawn from the same semantic categories as the targets (related distractors) and half are drawn from other categories (unrelated distractors). The number of correctly-recalled words in each trial is recorded (maximum of 12 per trial). The score is the sum of all the correctly-recalled words from each trial, for a maximum of 36. T-scores are reported (average T-score of 50 (ranges 40-60)
Time frame: Mean at baseline and 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LFR rTMS | Delayed Recall as Assessed by Hopkins Verbal Learning Test (HVLT) | Baseline | 44.364 T-score of correctly-recalled words | Standard Deviation 10.604 |
| LFR rTMS | Delayed Recall as Assessed by Hopkins Verbal Learning Test (HVLT) | 16 weeks | 49.111 T-score of correctly-recalled words | Standard Deviation 12.956 |
| Sham Treatment | Delayed Recall as Assessed by Hopkins Verbal Learning Test (HVLT) | Baseline | 43.071 T-score of correctly-recalled words | Standard Deviation 9.635 |
| Sham Treatment | Delayed Recall as Assessed by Hopkins Verbal Learning Test (HVLT) | 16 weeks | 47.692 T-score of correctly-recalled words | Standard Deviation 5.836 |
Secondary
Evaluation of Brain Injury as Assessed by the Trailmaking Test A Score
Trailmaking A is a psychological test with a score that is the number of seconds spent in connecting 25 numbered circles in sequential order. Score ranges from 0-150. Higher score reflects poorer outcome.
Time frame: Mean at baseline and 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LFR rTMS | Evaluation of Brain Injury as Assessed by the Trailmaking Test A Score | 16 weeks | 23.133 seconds | Standard Deviation 5.8 |
| LFR rTMS | Evaluation of Brain Injury as Assessed by the Trailmaking Test A Score | Baseline | 27.725 seconds | Standard Deviation 8.285 |
| Sham Treatment | Evaluation of Brain Injury as Assessed by the Trailmaking Test A Score | Baseline | 31.434 seconds | Standard Deviation 10.02 |
| Sham Treatment | Evaluation of Brain Injury as Assessed by the Trailmaking Test A Score | 16 weeks | 30.027 seconds | Standard Deviation 12.642 |
Secondary
Evaluation of Brain Injury as Assessed by the Trailmaking Test B Score
The Trailmaking B score is the number of seconds spent connecting numbered circles (1-13) to circles containing letters of the alphabet (A-L) in alternating sequential order. A maximum of 300 seconds is allowed. Score ranges from 0-300. Higher score reflects poorer outcome.
Time frame: Mean at baseline and 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LFR rTMS | Evaluation of Brain Injury as Assessed by the Trailmaking Test B Score | Baseline | 68.411 seconds | Standard Deviation 32.106 |
| LFR rTMS | Evaluation of Brain Injury as Assessed by the Trailmaking Test B Score | 16 weeks | 56.439 seconds | Standard Deviation 16.723 |
| Sham Treatment | Evaluation of Brain Injury as Assessed by the Trailmaking Test B Score | Baseline | 71.432 seconds | Standard Deviation 42.1 |
| Sham Treatment | Evaluation of Brain Injury as Assessed by the Trailmaking Test B Score | 16 weeks | 68.015 seconds | Standard Deviation 25.023 |
Secondary
Fatigue Severity as Assessed by the Fatigue Severity Scale (FSS)
The FSS is a 9-item questionnaire which measures the severity of fatigue and how it interferes with certain activities. The items are scored on a 7-point scale with 1=strongly disagree and 7=strongly agree. The score ranges from 9 to a maximum of 63. A higher score reflects greater fatigue severity.
Time frame: Mean at baseline, 4, 8, 12, and 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LFR rTMS | Fatigue Severity as Assessed by the Fatigue Severity Scale (FSS) | 4 weeks | 28.385 units on a scale | Standard Deviation 15.788 |
| LFR rTMS | Fatigue Severity as Assessed by the Fatigue Severity Scale (FSS) | 12 weeks | 23.25 units on a scale | Standard Deviation 11.787 |
| LFR rTMS | Fatigue Severity as Assessed by the Fatigue Severity Scale (FSS) | 8 weeks | 20.769 units on a scale | Standard Deviation 13.116 |
| LFR rTMS | Fatigue Severity as Assessed by the Fatigue Severity Scale (FSS) | 16 weeks | 21.23 units on a scale | Standard Deviation 13.02 |
| LFR rTMS | Fatigue Severity as Assessed by the Fatigue Severity Scale (FSS) | Baseline | 28.308 units on a scale | Standard Deviation 15.124 |
| Sham Treatment | Fatigue Severity as Assessed by the Fatigue Severity Scale (FSS) | 16 weeks | 29 units on a scale | Standard Deviation 17.274 |
| Sham Treatment | Fatigue Severity as Assessed by the Fatigue Severity Scale (FSS) | Baseline | 41.176 units on a scale | Standard Deviation 11.975 |
| Sham Treatment | Fatigue Severity as Assessed by the Fatigue Severity Scale (FSS) | 4 weeks | 23.375 units on a scale | Standard Deviation 15.362 |
| Sham Treatment | Fatigue Severity as Assessed by the Fatigue Severity Scale (FSS) | 8 weeks | 29.938 units on a scale | Standard Deviation 16.643 |
| Sham Treatment | Fatigue Severity as Assessed by the Fatigue Severity Scale (FSS) | 12 weeks | 27.286 units on a scale | Standard Deviation 18.168 |
Secondary
Immediate Recall as Assessed by Brief Visual Memory Test (BVMT)
BVMT is used to evaluate visuospatial memory abilities in neuropsychological populations. A visual display of six simple figures arranged in a 2 × 3 matrix on an 8 × 11 booklet is shown to participants for three consecutive 10-second trials. After each trial, participants are to draw as many designs as accurately as they can and in the correct location. Scoring of the immediate recall is based on the accuracy of the drawings and the location of the figures. For each figure, one point is awarded to each satisfactory domain resulting in a maximum of 12-points per trial, for a total score ranging from 0-36, with a higher score reflecting a better outcome.
Time frame: Mean at baseline and 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LFR rTMS | Immediate Recall as Assessed by Brief Visual Memory Test (BVMT) | Baseline | 22.846 accurately-drawn figures | Standard Deviation 9.547 |
| LFR rTMS | Immediate Recall as Assessed by Brief Visual Memory Test (BVMT) | 16 weeks | 23.231 accurately-drawn figures | Standard Deviation 8.833 |
| Sham Treatment | Immediate Recall as Assessed by Brief Visual Memory Test (BVMT) | Baseline | 24.313 accurately-drawn figures | Standard Deviation 7.355 |
| Sham Treatment | Immediate Recall as Assessed by Brief Visual Memory Test (BVMT) | 16 weeks | 21.438 accurately-drawn figures | Standard Deviation 6.593 |
Secondary
Immediate Recall as Assessed by Hopkins Verbal Learning Test (HVLT)
The Hopkins Verbal Learning Test (HVLT) consists of a 12-item word list, composed of four words from each of the three semantic categories. The subject is instructed to listen carefully as the examiner reads the word list and attempt to memorize the words. The word list is then read to the subject at the approximate rate of one word every 2 seconds. This is done for three trials. The number of correctly-recalled words in each trial is recorded (maximum of 12). The score is a sum of all the correctly-recalled words from each trial, for a maximum score of 36.
Time frame: Mean at baseline and 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LFR rTMS | Immediate Recall as Assessed by Hopkins Verbal Learning Test (HVLT) | Baseline | 23.077 sum of correctly-recalled words | Standard Deviation 5.722 |
| LFR rTMS | Immediate Recall as Assessed by Hopkins Verbal Learning Test (HVLT) | 16 weeks | 23.538 sum of correctly-recalled words | Standard Deviation 7.287 |
| Sham Treatment | Immediate Recall as Assessed by Hopkins Verbal Learning Test (HVLT) | Baseline | 25.938 sum of correctly-recalled words | Standard Deviation 5.285 |
| Sham Treatment | Immediate Recall as Assessed by Hopkins Verbal Learning Test (HVLT) | 16 weeks | 25.5 sum of correctly-recalled words | Standard Deviation 5.279 |
Secondary
Mean Cognitive Function as Assessed by the Montreal Cognitive Assessment (MOCA)
MOCA is designed to assess cognitive impairment and Alzheimer's Disease. It is composed of the following: Visuospatial and Executive Functioning: 5 points Animal Naming: 3 points Attention: 6 points Language: 3 points Abstraction: 2 points Delayed Recall (Short-term Memory): 5 points Orientation: 6 points Education Level: 1 point is added to the test-taker's score if he or she has 12 years or less of formal education. Score ranges 0-31, with ≥ 26 being normal cognitive function. The lower the score, the greater the level of cognitive impairment.
Time frame: Mean at baseline and 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LFR rTMS | Mean Cognitive Function as Assessed by the Montreal Cognitive Assessment (MOCA) | 16 weeks | 26 units on a scale | Standard Deviation 3.342 |
| LFR rTMS | Mean Cognitive Function as Assessed by the Montreal Cognitive Assessment (MOCA) | Baseline | 25.769 units on a scale | Standard Deviation 2.619 |
| Sham Treatment | Mean Cognitive Function as Assessed by the Montreal Cognitive Assessment (MOCA) | Baseline | 26.5 units on a scale | Standard Deviation 3.141 |
| Sham Treatment | Mean Cognitive Function as Assessed by the Montreal Cognitive Assessment (MOCA) | 16 weeks | 26.875 units on a scale | Standard Deviation 3.442 |
Secondary
Mean Generalized Anxiety Disorder (GAD) - 7 Questionnaire
The GAD-7 questionnaire is used as a screening tool and severity measure for generalized anxiety disorder. The scale ranges from 0 - 21. 0-4 = normal 5-9 = mild 10-14 = moderate \>15 = severe
Time frame: Baseline, 4, 8, 12, and 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LFR rTMS | Mean Generalized Anxiety Disorder (GAD) - 7 Questionnaire | 4 weeks | 7.5 units on a scale | Standard Deviation 6.375 |
| LFR rTMS | Mean Generalized Anxiety Disorder (GAD) - 7 Questionnaire | 12 weeks | 6.923 units on a scale | Standard Deviation 5.423 |
| LFR rTMS | Mean Generalized Anxiety Disorder (GAD) - 7 Questionnaire | 8 weeks | 6.917 units on a scale | Standard Deviation 6.417 |
| LFR rTMS | Mean Generalized Anxiety Disorder (GAD) - 7 Questionnaire | 16 weeks | 7.538 units on a scale | Standard Deviation 6.603 |
| LFR rTMS | Mean Generalized Anxiety Disorder (GAD) - 7 Questionnaire | Baseline | 12.636 units on a scale | Standard Deviation 4.61 |
| Sham Treatment | Mean Generalized Anxiety Disorder (GAD) - 7 Questionnaire | 16 weeks | 7.412 units on a scale | Standard Deviation 5.853 |
| Sham Treatment | Mean Generalized Anxiety Disorder (GAD) - 7 Questionnaire | Baseline | 12.75 units on a scale | Standard Deviation 5 |
| Sham Treatment | Mean Generalized Anxiety Disorder (GAD) - 7 Questionnaire | 4 weeks | 7.824 units on a scale | Standard Deviation 5.028 |
| Sham Treatment | Mean Generalized Anxiety Disorder (GAD) - 7 Questionnaire | 8 weeks | 7.588 units on a scale | Standard Deviation 5.874 |
| Sham Treatment | Mean Generalized Anxiety Disorder (GAD) - 7 Questionnaire | 12 weeks | 7.688 units on a scale | Standard Deviation 5.594 |
Secondary
Mean Level of Fatigue as Assessed by Patient Sleep Quality Index (PSQI)
The PSQI score scale ranges from 0-21. 0 = very good sleep quality 21 = very bad sleep quality A total score of 5 or greater is indicative of poor sleep quality (reflecting a higher level of fatigue)
Time frame: Baseline, 4, 8, 12, and 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LFR rTMS | Mean Level of Fatigue as Assessed by Patient Sleep Quality Index (PSQI) | 4 weeks | 10.23 units on a scale | Standard Deviation 4.585 |
| LFR rTMS | Mean Level of Fatigue as Assessed by Patient Sleep Quality Index (PSQI) | 12 weeks | 9.5 units on a scale | Standard Deviation 4.758 |
| LFR rTMS | Mean Level of Fatigue as Assessed by Patient Sleep Quality Index (PSQI) | 8 weeks | 9.846 units on a scale | Standard Deviation 4.356 |
| LFR rTMS | Mean Level of Fatigue as Assessed by Patient Sleep Quality Index (PSQI) | 16 weeks | 9.154 units on a scale | Standard Deviation 4.913 |
| LFR rTMS | Mean Level of Fatigue as Assessed by Patient Sleep Quality Index (PSQI) | Baseline | 13.846 units on a scale | Standard Deviation 3.848 |
| Sham Treatment | Mean Level of Fatigue as Assessed by Patient Sleep Quality Index (PSQI) | 16 weeks | 9.625 units on a scale | Standard Deviation 3.793 |
| Sham Treatment | Mean Level of Fatigue as Assessed by Patient Sleep Quality Index (PSQI) | Baseline | 13.688 units on a scale | Standard Deviation 3.591 |
| Sham Treatment | Mean Level of Fatigue as Assessed by Patient Sleep Quality Index (PSQI) | 4 weeks | 10.647 units on a scale | Standard Deviation 4.133 |
| Sham Treatment | Mean Level of Fatigue as Assessed by Patient Sleep Quality Index (PSQI) | 8 weeks | 10.176 units on a scale | Standard Deviation 2.877 |
| Sham Treatment | Mean Level of Fatigue as Assessed by Patient Sleep Quality Index (PSQI) | 12 weeks | 10.235 units on a scale | Standard Deviation 4.161 |
Secondary
Mean Level of Fatigue as Assessed by the Epworth Sleepiness Scale (ESS)
The ESS is used to determine the level of daytime sleepiness. It is a questionnaire composed of 8 questions. The participant answers each question on a scale of 0 to 3 (0=no sleepiness, 1= mild sleepiness, 2= moderate sleepiness, 3= severe sleepiness). The total score is the sum of all responses for a maximum score of 24. A higher score reflects increased sleepiness.
Time frame: Baseline, 4, 8, 12, and 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LFR rTMS | Mean Level of Fatigue as Assessed by the Epworth Sleepiness Scale (ESS) | 4 weeks | 5.846 units on a scale | Standard Deviation 4.896 |
| LFR rTMS | Mean Level of Fatigue as Assessed by the Epworth Sleepiness Scale (ESS) | 12 weeks | 6.667 units on a scale | Standard Deviation 5.015 |
| LFR rTMS | Mean Level of Fatigue as Assessed by the Epworth Sleepiness Scale (ESS) | 8 weeks | 5.923 units on a scale | Standard Deviation 3.883 |
| LFR rTMS | Mean Level of Fatigue as Assessed by the Epworth Sleepiness Scale (ESS) | 16 weeks | 6.077 units on a scale | Standard Deviation 4.609 |
| LFR rTMS | Mean Level of Fatigue as Assessed by the Epworth Sleepiness Scale (ESS) | Baseline | 9.769 units on a scale | Standard Deviation 4.746 |
| Sham Treatment | Mean Level of Fatigue as Assessed by the Epworth Sleepiness Scale (ESS) | 16 weeks | 6 units on a scale | Standard Deviation 3.857 |
| Sham Treatment | Mean Level of Fatigue as Assessed by the Epworth Sleepiness Scale (ESS) | Baseline | 9.412 units on a scale | Standard Deviation 6.81 |
| Sham Treatment | Mean Level of Fatigue as Assessed by the Epworth Sleepiness Scale (ESS) | 4 weeks | 7.563 units on a scale | Standard Deviation 4.381 |
| Sham Treatment | Mean Level of Fatigue as Assessed by the Epworth Sleepiness Scale (ESS) | 8 weeks | 6.063 units on a scale | Standard Deviation 3.586 |
| Sham Treatment | Mean Level of Fatigue as Assessed by the Epworth Sleepiness Scale (ESS) | 12 weeks | 7 units on a scale | Standard Deviation 4.536 |
Secondary
Mean Trauma Severity as Assessed by the Davidson Trauma Scale (DTS)
The DTS is a 17-item self-reported measure that assesses the 17 Diagnostic and Statistical Manual IV (DSM-IV) symptoms of post-traumatic stress disorder (PTSD). Items are rated on 5-point frequency (0 = not at all to 4 = every day) and severity scales (0 = not at all distressing to 4 = extremely distressing). The DTS yields a frequency score (ranging from 0 to 68), severity score (ranging from 0 to 68), and total score (ranging from 0 to 136). The severity score will be used to assess this outcome.
Time frame: Baseline, 4, 8, 12, and 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LFR rTMS | Mean Trauma Severity as Assessed by the Davidson Trauma Scale (DTS) | 4 weeks | 15 units on a scale | Standard Deviation 20.01 |
| LFR rTMS | Mean Trauma Severity as Assessed by the Davidson Trauma Scale (DTS) | 12 weeks | 14.833 units on a scale | Standard Deviation 22.938 |
| LFR rTMS | Mean Trauma Severity as Assessed by the Davidson Trauma Scale (DTS) | 8 weeks | 11.462 units on a scale | Standard Deviation 20.711 |
| LFR rTMS | Mean Trauma Severity as Assessed by the Davidson Trauma Scale (DTS) | 16 weeks | 16 units on a scale | Standard Deviation 29.243 |
| LFR rTMS | Mean Trauma Severity as Assessed by the Davidson Trauma Scale (DTS) | Baseline | 34.154 units on a scale | Standard Deviation 30.306 |
| Sham Treatment | Mean Trauma Severity as Assessed by the Davidson Trauma Scale (DTS) | 16 weeks | 18.647 units on a scale | Standard Deviation 32.581 |
| Sham Treatment | Mean Trauma Severity as Assessed by the Davidson Trauma Scale (DTS) | Baseline | 41.706 units on a scale | Standard Deviation 40.769 |
| Sham Treatment | Mean Trauma Severity as Assessed by the Davidson Trauma Scale (DTS) | 4 weeks | 24.063 units on a scale | Standard Deviation 33.657 |
| Sham Treatment | Mean Trauma Severity as Assessed by the Davidson Trauma Scale (DTS) | 8 weeks | 17.294 units on a scale | Standard Deviation 32.711 |
| Sham Treatment | Mean Trauma Severity as Assessed by the Davidson Trauma Scale (DTS) | 12 weeks | 27.125 units on a scale | Standard Deviation 33.478 |
Secondary
Overall Satisfaction With Life as Assessed by the Satisfaction With Life (SWL) Questionnaire
The SWL is a 7-point Likert-style response scale. The possible range of scores is 5-35, with a score of 20 representing a neutral point on the scale. Scores between 5-9 indicate the respondent is extremely dissatisfied with life, whereas scores between 31-35 indicate the respondent is extremely satisfied.
Time frame: Mean at baseline, 4, 8, 12, and 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LFR rTMS | Overall Satisfaction With Life as Assessed by the Satisfaction With Life (SWL) Questionnaire | 4 weeks | 21.538 units on a scale | Standard Deviation 8.511 |
| LFR rTMS | Overall Satisfaction With Life as Assessed by the Satisfaction With Life (SWL) Questionnaire | 12 weeks | 22 units on a scale | Standard Deviation 8.524 |
| LFR rTMS | Overall Satisfaction With Life as Assessed by the Satisfaction With Life (SWL) Questionnaire | 8 weeks | 22.231 units on a scale | Standard Deviation 8.207 |
| LFR rTMS | Overall Satisfaction With Life as Assessed by the Satisfaction With Life (SWL) Questionnaire | 16 weeks | 23.923 units on a scale | Standard Deviation 6.898 |
| LFR rTMS | Overall Satisfaction With Life as Assessed by the Satisfaction With Life (SWL) Questionnaire | Baseline | 14.231 units on a scale | Standard Deviation 7.132 |
| Sham Treatment | Overall Satisfaction With Life as Assessed by the Satisfaction With Life (SWL) Questionnaire | 16 weeks | 18.647 units on a scale | Standard Deviation 9.367 |
| Sham Treatment | Overall Satisfaction With Life as Assessed by the Satisfaction With Life (SWL) Questionnaire | Baseline | 10.625 units on a scale | Standard Deviation 4.015 |
| Sham Treatment | Overall Satisfaction With Life as Assessed by the Satisfaction With Life (SWL) Questionnaire | 4 weeks | 18.471 units on a scale | Standard Deviation 8.769 |
| Sham Treatment | Overall Satisfaction With Life as Assessed by the Satisfaction With Life (SWL) Questionnaire | 8 weeks | 17.647 units on a scale | Standard Deviation 9.88 |
| Sham Treatment | Overall Satisfaction With Life as Assessed by the Satisfaction With Life (SWL) Questionnaire | 12 weeks | 17 units on a scale | Standard Deviation 8.809 |
Secondary
Presence of Neuropsychiatric Symptoms as Assessed by Neurobehavioral Rating Scale (NBRS)
The NBRS is a 28-item interview which includes a test of orientation and memory for recent events, questions regarding emotional state, post-concussional symptoms, focused attention, and concentration (performing serial sevens), explanation of proverbs, tasks of planning and mental flexibility, and delayed recall of three objects presented at the beginning of a session. Observations are also made regarding the patient's fatigability, visible signs of anxiety, disinhibition, agitation, hostility, difficulties in expressive and receptive communication, and disturbance of mood. The balance of the items are rated according to the patient's performance on brief tasks and quality of answers to interview questions. Each of the 28 items are scored on a scale of 0 (not severe) to 6 (extremely severe), for a maximum score of 168. A higher score reflects increased severity of neuropsychiatric symptoms.
Time frame: Mean at baseline, 4, 8, 12, and 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LFR rTMS | Presence of Neuropsychiatric Symptoms as Assessed by Neurobehavioral Rating Scale (NBRS) | 4 weeks | 40.545 units on a scale | Standard Deviation 10.709 |
| LFR rTMS | Presence of Neuropsychiatric Symptoms as Assessed by Neurobehavioral Rating Scale (NBRS) | 12 weeks | 43.222 units on a scale | Standard Deviation 10.072 |
| LFR rTMS | Presence of Neuropsychiatric Symptoms as Assessed by Neurobehavioral Rating Scale (NBRS) | 8 weeks | 44.222 units on a scale | Standard Deviation 12.498 |
| LFR rTMS | Presence of Neuropsychiatric Symptoms as Assessed by Neurobehavioral Rating Scale (NBRS) | 16 weeks | 39.154 units on a scale | Standard Deviation 11.866 |
| LFR rTMS | Presence of Neuropsychiatric Symptoms as Assessed by Neurobehavioral Rating Scale (NBRS) | Baseline | 51.23 units on a scale | Standard Deviation 5.89 |
| Sham Treatment | Presence of Neuropsychiatric Symptoms as Assessed by Neurobehavioral Rating Scale (NBRS) | 16 weeks | 40.375 units on a scale | Standard Deviation 10.513 |
| Sham Treatment | Presence of Neuropsychiatric Symptoms as Assessed by Neurobehavioral Rating Scale (NBRS) | Baseline | 56.125 units on a scale | Standard Deviation 10.683 |
| Sham Treatment | Presence of Neuropsychiatric Symptoms as Assessed by Neurobehavioral Rating Scale (NBRS) | 4 weeks | 40.727 units on a scale | Standard Deviation 7.837 |
| Sham Treatment | Presence of Neuropsychiatric Symptoms as Assessed by Neurobehavioral Rating Scale (NBRS) | 8 weeks | 42.786 units on a scale | Standard Deviation 13.116 |
| Sham Treatment | Presence of Neuropsychiatric Symptoms as Assessed by Neurobehavioral Rating Scale (NBRS) | 12 weeks | 39.273 units on a scale | Standard Deviation 9.056 |
Secondary
Presence of Post-concussive Symptoms as Assessed by the Rivermead Post-Concussion Questionnaire (RPQ)
Participants are asked to rate the severity of 16 different symptoms over the past 24 hours, on a severity scale from 0 to 4 (0 = not experienced, 1 = no more of a problem, 2 = mild problem, 3 = moderate problem, 4 = severe problem). The 16 symptoms include: headaches, dizziness, nausea and/or vomiting, hyperacusis, sleep disturbance, fatigue, being irritable, feeling depressed, feeling frustrated, forgetfulness, poor concentration, taking longer to think, blurred vision, light sensitivity, double vision, restlessness. Score ranges from 0 to 64, with a higher score reflecting increased severity of post-concussive symptoms.
Time frame: Mean at baseline, 4, 8, 12, and 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LFR rTMS | Presence of Post-concussive Symptoms as Assessed by the Rivermead Post-Concussion Questionnaire (RPQ) | 4 weeks | 11.833 units on a scale | Standard Deviation 8.747 |
| LFR rTMS | Presence of Post-concussive Symptoms as Assessed by the Rivermead Post-Concussion Questionnaire (RPQ) | 12 weeks | 12.75 units on a scale | Standard Deviation 12.009 |
| LFR rTMS | Presence of Post-concussive Symptoms as Assessed by the Rivermead Post-Concussion Questionnaire (RPQ) | 8 weeks | 14.154 units on a scale | Standard Deviation 11.753 |
| LFR rTMS | Presence of Post-concussive Symptoms as Assessed by the Rivermead Post-Concussion Questionnaire (RPQ) | 16 weeks | 10.538 units on a scale | Standard Deviation 7.817 |
| LFR rTMS | Presence of Post-concussive Symptoms as Assessed by the Rivermead Post-Concussion Questionnaire (RPQ) | Baseline | 26.769 units on a scale | Standard Deviation 8.719 |
| Sham Treatment | Presence of Post-concussive Symptoms as Assessed by the Rivermead Post-Concussion Questionnaire (RPQ) | 16 weeks | 14.294 units on a scale | Standard Deviation 14.886 |
| Sham Treatment | Presence of Post-concussive Symptoms as Assessed by the Rivermead Post-Concussion Questionnaire (RPQ) | Baseline | 23.125 units on a scale | Standard Deviation 14.184 |
| Sham Treatment | Presence of Post-concussive Symptoms as Assessed by the Rivermead Post-Concussion Questionnaire (RPQ) | 4 weeks | 11.765 units on a scale | Standard Deviation 9.451 |
| Sham Treatment | Presence of Post-concussive Symptoms as Assessed by the Rivermead Post-Concussion Questionnaire (RPQ) | 8 weeks | 11 units on a scale | Standard Deviation 8.075 |
| Sham Treatment | Presence of Post-concussive Symptoms as Assessed by the Rivermead Post-Concussion Questionnaire (RPQ) | 12 weeks | 11.857 units on a scale | Standard Deviation 10.369 |
Secondary
Presence of Social Connections as Assessed by the Social Ties Checklist (STC)
The STC reflects the level of social contact. The score ranges from 0-10, with 0= excellent contact, 10=no contact. A higher score reflects poorer social contact.
Time frame: Mean at baseline, 4, 8, 12, and 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LFR rTMS | Presence of Social Connections as Assessed by the Social Ties Checklist (STC) | 4 weeks | 3.077 units on a scale | Standard Deviation 1.706 |
| LFR rTMS | Presence of Social Connections as Assessed by the Social Ties Checklist (STC) | 12 weeks | 2.846 units on a scale | Standard Deviation 1.573 |
| LFR rTMS | Presence of Social Connections as Assessed by the Social Ties Checklist (STC) | 8 weeks | 2.769 units on a scale | Standard Deviation 1.536 |
| LFR rTMS | Presence of Social Connections as Assessed by the Social Ties Checklist (STC) | 16 weeks | 2.846 units on a scale | Standard Deviation 1.676 |
| LFR rTMS | Presence of Social Connections as Assessed by the Social Ties Checklist (STC) | Baseline | 3.154 units on a scale | Standard Deviation 1.573 |
| Sham Treatment | Presence of Social Connections as Assessed by the Social Ties Checklist (STC) | 16 weeks | 3.471 units on a scale | Standard Deviation 2.065 |
| Sham Treatment | Presence of Social Connections as Assessed by the Social Ties Checklist (STC) | Baseline | 4.563 units on a scale | Standard Deviation 2.065 |
| Sham Treatment | Presence of Social Connections as Assessed by the Social Ties Checklist (STC) | 4 weeks | 3.765 units on a scale | Standard Deviation 1.855 |
| Sham Treatment | Presence of Social Connections as Assessed by the Social Ties Checklist (STC) | 8 weeks | 3.471 units on a scale | Standard Deviation 1.7 |
| Sham Treatment | Presence of Social Connections as Assessed by the Social Ties Checklist (STC) | 12 weeks | 3.688 units on a scale | Standard Deviation 2.243 |