Trial Outcomes & Findings for Managing Mild Traumatic Brain Injury Related Headaches With Repetitive Transcranial Magnetic Stimulation (NCT NCT03314584)

NCT ID: NCT03314584

Last Updated: 2025-08-07

Results Overview

The outcome measure will be quantified through the headache diary log that tracks the intensity, frequency and duration of MTBI-headaches (MTBI-HA). Baseline data includes all logs from the start of the study until the start of treatment. Post-intervention data looked at the time between the 3-month follow-up and the previous visit.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

179 participants

Primary outcome timeframe

The measure will be assessed daily from baseline to the 3-month post-treatment follow up (treatment occurred for 2-5 weeks starting in week 3).

Results posted on

2025-08-07

Participant Flow

Participant milestones

Participant milestones
Measure
Transcranial Magnetic Stimulation
Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex. Transcranial Magnetic Stimulation: Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex. Magnetic resonance imaging (MRI): Brain imaging will be done via MRI prior to the first rTMS/Sham TMS session. Imaging will allow investigators to target specific areas in the brain.
Sham Transcranial Magnetic Stimulation
Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex. Sham Transcranial Magnetic Stimulation: Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex due to the use of a double sided Active/Sham coil used specifically for research studies. Magnetic resonance imaging (MRI): Brain imaging will be done via MRI prior to the first rTMS/Sham TMS session. Imaging will allow investigators to target specific areas in the brain.
Overall Study
STARTED
38
41
Overall Study
COMPLETED
31
38
Overall Study
NOT COMPLETED
7
3

Reasons for withdrawal

Reasons for withdrawal
Measure
Transcranial Magnetic Stimulation
Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex. Transcranial Magnetic Stimulation: Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex. Magnetic resonance imaging (MRI): Brain imaging will be done via MRI prior to the first rTMS/Sham TMS session. Imaging will allow investigators to target specific areas in the brain.
Sham Transcranial Magnetic Stimulation
Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex. Sham Transcranial Magnetic Stimulation: Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex due to the use of a double sided Active/Sham coil used specifically for research studies. Magnetic resonance imaging (MRI): Brain imaging will be done via MRI prior to the first rTMS/Sham TMS session. Imaging will allow investigators to target specific areas in the brain.
Overall Study
Withdrawal by Subject
3
3
Overall Study
Lost to Follow-up
4
0

Baseline Characteristics

Managing Mild Traumatic Brain Injury Related Headaches With Repetitive Transcranial Magnetic Stimulation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Transcranial Magnetic Stimulation
n=32 Participants
Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex. Transcranial Magnetic Stimulation: Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex. Magnetic resonance imaging (MRI): Brain imaging will be done via MRI prior to the first rTMS/Sham TMS session. Imaging will allow investigators to target specific areas in the brain.
Sham Transcranial Magnetic Stimulation
n=38 Participants
Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex. Sham Transcranial Magnetic Stimulation: Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex due to the use of a double sided Active/Sham coil used specifically for research studies. Magnetic resonance imaging (MRI): Brain imaging will be done via MRI prior to the first rTMS/Sham TMS session. Imaging will allow investigators to target specific areas in the brain.
Total
n=70 Participants
Total of all reporting groups
Race (NIH/OMB)
Unknown or Not Reported
2 Participants
n=5 Participants
5 Participants
n=7 Participants
7 Participants
n=5 Participants
Region of Enrollment
United States
32 Participants
n=5 Participants
38 Participants
n=7 Participants
70 Participants
n=5 Participants
Age, Continuous
37.88 years
STANDARD_DEVIATION 11.07 • n=5 Participants
40.76 years
STANDARD_DEVIATION 7.76 • n=7 Participants
39.44 years
STANDARD_DEVIATION 9.46 • n=5 Participants
Sex: Female, Male
Female
6 Participants
n=5 Participants
6 Participants
n=7 Participants
12 Participants
n=5 Participants
Sex: Female, Male
Male
26 Participants
n=5 Participants
32 Participants
n=7 Participants
58 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
5 Participants
n=5 Participants
8 Participants
n=7 Participants
13 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
24 Participants
n=5 Participants
28 Participants
n=7 Participants
52 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
3 Participants
n=5 Participants
2 Participants
n=7 Participants
5 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
1 Participants
n=5 Participants
3 Participants
n=7 Participants
4 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
2 Participants
n=5 Participants
2 Participants
n=7 Participants
4 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
4 Participants
n=5 Participants
5 Participants
n=7 Participants
9 Participants
n=5 Participants
Race (NIH/OMB)
White
23 Participants
n=5 Participants
23 Participants
n=7 Participants
46 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants

PRIMARY outcome

Timeframe: The measure will be assessed daily from baseline to the 3-month post-treatment follow up (treatment occurred for 2-5 weeks starting in week 3).

Population: Some subjects are missing their 3-month follow up data due to it not being collected.

The outcome measure will be quantified through the headache diary log that tracks the intensity, frequency and duration of MTBI-headaches (MTBI-HA). Baseline data includes all logs from the start of the study until the start of treatment. Post-intervention data looked at the time between the 3-month follow-up and the previous visit.

Outcome measures

Outcome measures
Measure
Transcranial Magnetic Stimulation
n=32 Participants
Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex. Transcranial Magnetic Stimulation: Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex. Magnetic resonance imaging (MRI): Brain imaging will be done via MRI prior to the first rTMS/Sham TMS session. Imaging will allow investigators to target specific areas in the brain.
Sham Transcranial Magnetic Stimulation
n=38 Participants
Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex. Sham Transcranial Magnetic Stimulation: Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex due to the use of a double sided Active/Sham coil used specifically for research studies. Magnetic resonance imaging (MRI): Brain imaging will be done via MRI prior to the first rTMS/Sham TMS session. Imaging will allow investigators to target specific areas in the brain.
Number of Headache Days Per Week
Pre-intervention persistent headache frequency
4.2 days/week
Standard Deviation 2.9
4.6 days/week
Standard Deviation 2.0
Number of Headache Days Per Week
Post-intervention (3-months after TX) persistent headache frequency
3.1 days/week
Standard Deviation 2.3
4.3 days/week
Standard Deviation 1.9

PRIMARY outcome

Timeframe: The measure will be assessed daily from baseline to the 3-month post-treatment follow up (treatment occurred for 2-5 weeks starting in week 3).

Population: Some subjects were excluded from the pre-intervention or post-intervention data due to missing data. Subjects did not need both to be included in the analysis. The number analyzed below reflects that total subjects with valid data for that group and time point.

The outcome measure will be quantified through the headache diary log that tracks the intensity, frequency and duration of MTBI-headaches (MTBI-HA). Baseline data includes all logs from the start of the study until the start of treatment. Post-intervention data looked at the time between the 3-month follow-up and the previous visit.

Outcome measures

Outcome measures
Measure
Transcranial Magnetic Stimulation
n=30 Participants
Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex. Transcranial Magnetic Stimulation: Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex. Magnetic resonance imaging (MRI): Brain imaging will be done via MRI prior to the first rTMS/Sham TMS session. Imaging will allow investigators to target specific areas in the brain.
Sham Transcranial Magnetic Stimulation
n=38 Participants
Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex. Sham Transcranial Magnetic Stimulation: Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex due to the use of a double sided Active/Sham coil used specifically for research studies. Magnetic resonance imaging (MRI): Brain imaging will be done via MRI prior to the first rTMS/Sham TMS session. Imaging will allow investigators to target specific areas in the brain.
Number of Days With Debilitating MTBI-headaches Per Week.
Pre-intervention debilitating headache frequency
2.1 days/week
Standard Deviation 2.0
2.1 days/week
Standard Deviation 1.9
Number of Days With Debilitating MTBI-headaches Per Week.
Post-intervention (3-months after TX) debilitating headache frequency
1.3 days/week
Standard Deviation 1.8
1.8 days/week
Standard Deviation 1.7

PRIMARY outcome

Timeframe: The measure will be assessed daily from baseline to the 3-month post-treatment follow up (treatments occurred for 2-5 weeks starting in week 3).

Population: Some subjects were excluded from the pre-intervention or post-intervention data due to missing data. Subjects did not need both to be included in the analysis. The number analyzed below reflects that total subjects with valid data for that group and time point.

The outcome measure will be quantified through the headache diary log that tracks the intensity, frequency and duration of MTBI-headaches (MTBI-HA). Baseline data includes all logs from the start of the study until the start of treatment. Post-intervention data looked at the time between the 3-month follow-up and the previous visit.

Outcome measures

Outcome measures
Measure
Transcranial Magnetic Stimulation
n=30 Participants
Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex. Transcranial Magnetic Stimulation: Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex. Magnetic resonance imaging (MRI): Brain imaging will be done via MRI prior to the first rTMS/Sham TMS session. Imaging will allow investigators to target specific areas in the brain.
Sham Transcranial Magnetic Stimulation
n=38 Participants
Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex. Sham Transcranial Magnetic Stimulation: Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex due to the use of a double sided Active/Sham coil used specifically for research studies. Magnetic resonance imaging (MRI): Brain imaging will be done via MRI prior to the first rTMS/Sham TMS session. Imaging will allow investigators to target specific areas in the brain.
Duration of Debilitating MTBI-headaches (Hours).
Pre-intervention debilitating headache duration
3.5 hours
Standard Deviation 1.6
5.5 hours
Standard Deviation 4.6
Duration of Debilitating MTBI-headaches (Hours).
Post-intervention (3-months after TX) debilitating headache duration
4.3 hours
Standard Deviation 3.3
5.0 hours
Standard Deviation 4.3

PRIMARY outcome

Timeframe: The measure will be assessed daily from baseline to the 3-month post-treatment follow up (treatment occurred for 2-5 weeks starting in week 3).

Population: Some subjects were excluded from the pre-intervention or post-intervention data due to missing data. Subjects did not need both to be included in the analysis. The number analyzed below reflects that total subjects with valid data for that group and time point.

The outcome measure will be quantified through the headache diary log that tracks the intensity, frequency, duration, and interference of MTBI-headaches (MTBI-HA). A score of 0 for interference would indicate no interference in daily activities while a score of 10 would indicate complete interference (e.g. the subject could not get out of bed and go to work due to their pain). Baseline data includes all logs from the start of the study until the start of treatment. Post-intervention data looked at the time between the 3-month follow-up and the previous visit.

Outcome measures

Outcome measures
Measure
Transcranial Magnetic Stimulation
n=30 Participants
Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex. Transcranial Magnetic Stimulation: Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex. Magnetic resonance imaging (MRI): Brain imaging will be done via MRI prior to the first rTMS/Sham TMS session. Imaging will allow investigators to target specific areas in the brain.
Sham Transcranial Magnetic Stimulation
n=38 Participants
Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex. Sham Transcranial Magnetic Stimulation: Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex due to the use of a double sided Active/Sham coil used specifically for research studies. Magnetic resonance imaging (MRI): Brain imaging will be done via MRI prior to the first rTMS/Sham TMS session. Imaging will allow investigators to target specific areas in the brain.
Average Interference (0-10) of Headaches in Daily Activities.
Pre-intervention debilitating headache interference
6.9 score on a scale
Standard Deviation 1.5
6.6 score on a scale
Standard Deviation 1.8
Average Interference (0-10) of Headaches in Daily Activities.
Post-intervention (3-months after TX) debilitating headache interference
5.8 score on a scale
Standard Deviation 2.1
5.7 score on a scale
Standard Deviation 2.6

PRIMARY outcome

Timeframe: The measure will be assessed every visit from baseline to the 3-month post-treatment follow up (treatment occurred for 2-5 weeks starting in week 3).

Population: Some subjects were excluded from the pre-intervention or post-intervention data due to missing data. Subjects did not need both to be included in the analysis. The number analyzed below reflects that total subjects with valid data for that group and time point.

The outcome measure is measuring headache impact on quality of life and will be quantified through the self-assessed Headache Impact Test (HIT-6). Each question ranges from 6-13 and the total score ranges from 36 to 78. The assessment indicates the effect that headaches have on normal daily life and ability to function with a higher score indicating more interference in daily life and function.

Outcome measures

Outcome measures
Measure
Transcranial Magnetic Stimulation
n=32 Participants
Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex. Transcranial Magnetic Stimulation: Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex. Magnetic resonance imaging (MRI): Brain imaging will be done via MRI prior to the first rTMS/Sham TMS session. Imaging will allow investigators to target specific areas in the brain.
Sham Transcranial Magnetic Stimulation
n=38 Participants
Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex. Sham Transcranial Magnetic Stimulation: Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex due to the use of a double sided Active/Sham coil used specifically for research studies. Magnetic resonance imaging (MRI): Brain imaging will be done via MRI prior to the first rTMS/Sham TMS session. Imaging will allow investigators to target specific areas in the brain.
Baseline vs Post-Treatment HIT-6 Scores (36-78).
Pre-intervention HIT-6 total score.
65.2 score on a scale
Standard Deviation 4.8
65.1 score on a scale
Standard Deviation 6.5
Baseline vs Post-Treatment HIT-6 Scores (36-78).
Post-intervention (3-months post TX) HIT-6 total score.
60.7 score on a scale
Standard Deviation 8.8
60.3 score on a scale
Standard Deviation 8.8

PRIMARY outcome

Timeframe: The measure will be assessed each visit from baseline to the 3-month post-treatment follow up (treatment occurred for 2-5 weeks starting in week 3).

Population: Some subjects were excluded from the pre-intervention or post-intervention data due to missing data. Subjects did not need both to be included in the analysis. The number analyzed below reflects that total subjects with valid data for that group and time point.

The outcome measure will be measuring depression scores and will be quantified through the administered Hamilton Scale for Depression. This contains 17 items to be rated (HDRS-17), but four other questions are not added to the total score and are used to provide additional clinical information. Each item on the questionnaire is scored on a 3 or 5 point scale, depending on the item, and the total score is compared to the corresponding descriptor. The total score ranges from 0 to 53 and is calculated from adding together the first 17 questions. A higher score indicated more severe depression.

Outcome measures

Outcome measures
Measure
Transcranial Magnetic Stimulation
n=33 Participants
Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex. Transcranial Magnetic Stimulation: Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex. Magnetic resonance imaging (MRI): Brain imaging will be done via MRI prior to the first rTMS/Sham TMS session. Imaging will allow investigators to target specific areas in the brain.
Sham Transcranial Magnetic Stimulation
n=38 Participants
Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex. Sham Transcranial Magnetic Stimulation: Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex due to the use of a double sided Active/Sham coil used specifically for research studies. Magnetic resonance imaging (MRI): Brain imaging will be done via MRI prior to the first rTMS/Sham TMS session. Imaging will allow investigators to target specific areas in the brain.
Change From Baseline to Post-Treatment HDRS-17 Scores
Pre-intervention HRSD total score.
14.5 score on a scale
Standard Deviation 7.4
16.5 score on a scale
Standard Deviation 7.1
Change From Baseline to Post-Treatment HDRS-17 Scores
Post-intervention (3-months post TX) HRSD total score.
11.8 score on a scale
Standard Deviation 8.8
12.3 score on a scale
Standard Deviation 7.8

PRIMARY outcome

Timeframe: The measure will be assessed every visit from baseline to the 3-month post-treatment follow up (treatment occurred for 2-5 weeks starting in week 3).

Population: Some subjects were excluded from the pre-intervention or post-intervention data due to missing data. Subjects did not need both to be included in the analysis. The number analyzed below reflects that total subjects with valid data for that group and time point.

The outcome measure quantified through the Connors continuous performance test will be sustained and selective attention. This is administered on a laptop and is automatically scored. Key performance indicators are reported as T-scores (mean of 50, SD = 10) and percentiles. T-scores are compared to the normative sample. Variability measure which looked at response speed consistency and indicated fluctuations in attention. A higher score indicated more fluctuations.

Outcome measures

Outcome measures
Measure
Transcranial Magnetic Stimulation
n=26 Participants
Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex. Transcranial Magnetic Stimulation: Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex. Magnetic resonance imaging (MRI): Brain imaging will be done via MRI prior to the first rTMS/Sham TMS session. Imaging will allow investigators to target specific areas in the brain.
Sham Transcranial Magnetic Stimulation
n=32 Participants
Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex. Sham Transcranial Magnetic Stimulation: Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex due to the use of a double sided Active/Sham coil used specifically for research studies. Magnetic resonance imaging (MRI): Brain imaging will be done via MRI prior to the first rTMS/Sham TMS session. Imaging will allow investigators to target specific areas in the brain.
Connors Continuous Performance Test Score.
Pre-intervention CPT-3 Variability score.
58.0 T-Score
Standard Deviation 15.2
66.1 T-Score
Standard Deviation 19.0
Connors Continuous Performance Test Score.
Post-intervention (3-months post TX) CPT-3 Variability score.
61.3 T-Score
Standard Deviation 18.8
56.1 T-Score
Standard Deviation 12.9

PRIMARY outcome

Timeframe: The measure will be assessed every visit from baseline to the 3-month post-treatment follow up (treatment occurred for 2-5 weeks starting in week 3).

Population: Some subjects were excluded from the pre-intervention or post-intervention data due to missing data. Subjects did not need both to be included in the analysis. The number analyzed below reflects that total subjects with valid data for that group and time point.

The outcome will measure global pain through the brief pain inventory assessment. Pain will be recorded at it's worst, it's best and on average over the previous 24 hours on a 0 to 10 scale These scores are reflected in questions 3-6 of the assessment and will be averaged together to give an overall average pain level score with a higher value reflecting more pain. Then the pain's impact on general activity, mood, walking ability, normal work, relationships, sleep and enjoyment of life will be measured on a 0 to 10 scale and averaged for an overall pain score. These scores are reflected in question 9a-g and will be averaged together to give an overall average pain interference level with a higher value indicating more interference in daily life.

Outcome measures

Outcome measures
Measure
Transcranial Magnetic Stimulation
n=25 Participants
Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex. Transcranial Magnetic Stimulation: Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex. Magnetic resonance imaging (MRI): Brain imaging will be done via MRI prior to the first rTMS/Sham TMS session. Imaging will allow investigators to target specific areas in the brain.
Sham Transcranial Magnetic Stimulation
n=33 Participants
Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex. Sham Transcranial Magnetic Stimulation: Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex due to the use of a double sided Active/Sham coil used specifically for research studies. Magnetic resonance imaging (MRI): Brain imaging will be done via MRI prior to the first rTMS/Sham TMS session. Imaging will allow investigators to target specific areas in the brain.
Brief Pain Inventory Global Score.
Pre-intervention BPI overall score.
5.1 score on a scale
Standard Deviation 1.4
5.5 score on a scale
Standard Deviation 1.8
Brief Pain Inventory Global Score.
Post-intervention (3-months post TX) BPI overall score.
4.2 score on a scale
Standard Deviation 2.6
4.3 score on a scale
Standard Deviation 2.4

PRIMARY outcome

Timeframe: The measure will be assessed every visit from baseline to the 3-month post-treatment follow up (treatment occurred for 2-5 weeks starting in week 3).

Population: Some subjects were excluded from the pre-intervention or post-intervention data due to missing data. Subjects did not need both to be included in the analysis. The number analyzed below reflects that total subjects with valid data for that group and time point.

The Hopkins Verbal Learning Test (HVLT-R) will be used to measure memory. In this assessment, 12 words are taught and subjects are tasked to recall those words in three difference trials. When scoring the HVLT-R, the number of words recalled are summed to calculate a total recall score which ranges from 0-36 with higher values indicating more words being recalled.

Outcome measures

Outcome measures
Measure
Transcranial Magnetic Stimulation
n=33 Participants
Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex. Transcranial Magnetic Stimulation: Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex. Magnetic resonance imaging (MRI): Brain imaging will be done via MRI prior to the first rTMS/Sham TMS session. Imaging will allow investigators to target specific areas in the brain.
Sham Transcranial Magnetic Stimulation
n=38 Participants
Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex. Sham Transcranial Magnetic Stimulation: Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex due to the use of a double sided Active/Sham coil used specifically for research studies. Magnetic resonance imaging (MRI): Brain imaging will be done via MRI prior to the first rTMS/Sham TMS session. Imaging will allow investigators to target specific areas in the brain.
Hopkins Verbal Learning Test (HVLT-R) Total Scores
Pre-intervention HVLT-R total recall score.
23.5 score on a scale
Standard Deviation 4.6
21.9 score on a scale
Standard Deviation 5.4
Hopkins Verbal Learning Test (HVLT-R) Total Scores
Post-intervention (3-months post TX) HVLT-R total recall score.
24.2 score on a scale
Standard Deviation 5.8
23.7 score on a scale
Standard Deviation 6.7

PRIMARY outcome

Timeframe: The measure will be assessed every visit from baseline to the 3-month post-treatment follow up (treatment occurred for 2-5 weeks starting in week 3).

Population: Some subjects were excluded from the pre-intervention or post-intervention data due to missing data. Subjects did not need both to be included in the analysis. The number analyzed below reflects that total subjects with valid data for that group and time point.

The Stroop test was administered to assess cognitive functioning performance. In the test, the participant must demonstrate inhibition of cognitive interference by naming the color of the colored word instead of the word itself based on the observation that normal individuals can read words much faster than they can identify and name colors. This follows two other trials where the participant just reads the words aloud and another trial of the participant just identifying the color of a series of x's. Each trial, the participant was given 45 second to identify as many colors as they could. There is no maximum score for this assessment. This assessment is scored by the number of items they were able to correctly read out rather than on a T-score. A higher score indicated higher cognitive functioning.

Outcome measures

Outcome measures
Measure
Transcranial Magnetic Stimulation
n=27 Participants
Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex. Transcranial Magnetic Stimulation: Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex. Magnetic resonance imaging (MRI): Brain imaging will be done via MRI prior to the first rTMS/Sham TMS session. Imaging will allow investigators to target specific areas in the brain.
Sham Transcranial Magnetic Stimulation
n=31 Participants
Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex. Sham Transcranial Magnetic Stimulation: Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex due to the use of a double sided Active/Sham coil used specifically for research studies. Magnetic resonance imaging (MRI): Brain imaging will be done via MRI prior to the first rTMS/Sham TMS session. Imaging will allow investigators to target specific areas in the brain.
Stroop Test Score
Pre-intervention Stroop color word total score.
36.6 Number of words
Standard Deviation 13.0
37.2 Number of words
Standard Deviation 14.2
Stroop Test Score
Post-intervention (3-months post TX) Stroop color word total score.
44.2 Number of words
Standard Deviation 12.2
43.6 Number of words
Standard Deviation 9.5

PRIMARY outcome

Timeframe: The measure will be assessed daily from baseline to the 3-month post-treatment follow up (treatment occurred for 2-5 weeks starting in week 3).

Population: Some subjects were excluded from the pre-intervention or post-intervention data due to missing data. Subjects did not need both to be included in the analysis. The number analyzed below reflects that total subjects with valid data for that group and time point.

The outcome measure will be quantified through the headache diary log that tracks the intensity, frequency and duration of MTBI-headaches (MTBI-HA). Intensity was rated on a scale of 0-10 with 0 indicating no pain and 10 indicating the worst pain they have experienced. Baseline data includes all logs from the start of the study until the start of treatment. Post-intervention data looked at the time between the 3-month follow-up and the previous visit.

Outcome measures

Outcome measures
Measure
Transcranial Magnetic Stimulation
n=32 Participants
Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex. Transcranial Magnetic Stimulation: Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex. Magnetic resonance imaging (MRI): Brain imaging will be done via MRI prior to the first rTMS/Sham TMS session. Imaging will allow investigators to target specific areas in the brain.
Sham Transcranial Magnetic Stimulation
n=38 Participants
Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex. Sham Transcranial Magnetic Stimulation: Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex due to the use of a double sided Active/Sham coil used specifically for research studies. Magnetic resonance imaging (MRI): Brain imaging will be done via MRI prior to the first rTMS/Sham TMS session. Imaging will allow investigators to target specific areas in the brain.
Average Intensity of Persistent Headaches.
Pre-intervention persistent headache intensity
5.0 score on a scale
Standard Deviation 1.3
4.7 score on a scale
Standard Deviation 1.5
Average Intensity of Persistent Headaches.
Post-intervention (3-months after TX) persistent headache Intensity
3.8 score on a scale
Standard Deviation 1.5
3.9 score on a scale
Standard Deviation 1.7

PRIMARY outcome

Timeframe: The measure will be assessed daily from baseline to the 3-month post-treatment follow up (treatment occurred for 2-5 weeks starting in week 3).

Population: Some subjects were excluded from the pre-intervention or post-intervention data due to missing data. Subjects did not need both to be included in the analysis. The number analyzed below reflects that total subjects with valid data for that group and time point.

The outcome measure will be quantified through the headache diary log that tracks the intensity, frequency and duration of MTBI-headaches (MTBI-HA). Intensity was rated on a scale of 0-10 with 0 indicating no pain and 10 indicating the worst pain they have experience. Baseline data includes all logs from the start of the study until the start of treatment. Post-intervention data looked at the time between the 3-month follow-up and the previous visit.

Outcome measures

Outcome measures
Measure
Transcranial Magnetic Stimulation
n=32 Participants
Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex. Transcranial Magnetic Stimulation: Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex. Magnetic resonance imaging (MRI): Brain imaging will be done via MRI prior to the first rTMS/Sham TMS session. Imaging will allow investigators to target specific areas in the brain.
Sham Transcranial Magnetic Stimulation
n=38 Participants
Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex. Sham Transcranial Magnetic Stimulation: Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex due to the use of a double sided Active/Sham coil used specifically for research studies. Magnetic resonance imaging (MRI): Brain imaging will be done via MRI prior to the first rTMS/Sham TMS session. Imaging will allow investigators to target specific areas in the brain.
Average Intensity of Debilitating Headaches.
Pre-intervention debilitating headache intensity
6.6 score on a scale
Standard Deviation 1.6
6.5 score on a scale
Standard Deviation 1.7
Average Intensity of Debilitating Headaches.
Post-intervention (3-months after TX) debilitating headache Intensity
5.8 score on a scale
Standard Deviation 2.0
5.7 score on a scale
Standard Deviation 2.4

SECONDARY outcome

Timeframe: Subjects will have 2 functional magnetic imaging scans, at baseline and then at the 1-week post treatment follow-up.

Population: Some subjects were excluded due to not having a resting state MRI scan performed.

Resting state functional magnetic imaging scans and subsequent processing using CONN Toolbox were used to determine T-values. ROIs (region of interest) where determined and compared to other ROIs to assess connectivity between regions. Value of "0" indicated no significant connectivity between regions (p\<0.01). The sign of the value indicated directionality of connectivity. Larger absolute values of the T-value indicated stronger connectivity.

Outcome measures

Outcome measures
Measure
Transcranial Magnetic Stimulation
n=28 Participants
Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex. Transcranial Magnetic Stimulation: Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex. Magnetic resonance imaging (MRI): Brain imaging will be done via MRI prior to the first rTMS/Sham TMS session. Imaging will allow investigators to target specific areas in the brain.
Sham Transcranial Magnetic Stimulation
n=35 Participants
Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex. Sham Transcranial Magnetic Stimulation: Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex due to the use of a double sided Active/Sham coil used specifically for research studies. Magnetic resonance imaging (MRI): Brain imaging will be done via MRI prior to the first rTMS/Sham TMS session. Imaging will allow investigators to target specific areas in the brain.
Significant T-Values for Connectivity Between Regions.
Left Motor Cortex (BA4) to Premotor (BA46)
-3.23 T-value
-3.61 T-value
Significant T-Values for Connectivity Between Regions.
Left Motor Cortex (BA4) to Insula (BA13)
6.57 T-value
5.50 T-value
Significant T-Values for Connectivity Between Regions.
Left Motor Cortex (BA4) to Cingulate (BA24-31)
4.06 T-value
6.12 T-value
Significant T-Values for Connectivity Between Regions.
Left Motor Cortex (BA4) to Premotor (BA6)
8.77 T-value
8.76 T-value
Significant T-Values for Connectivity Between Regions.
Left Motor Cortex (BA4) to Somatosensory (BA7)
2.85 T-value
0 T-value

Adverse Events

Transcranial Magnetic Stimulation

Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths

Sham Transcranial Magnetic Stimulation

Serious events: 2 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Transcranial Magnetic Stimulation
n=38 participants at risk
Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex. Transcranial Magnetic Stimulation: Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex. Magnetic resonance imaging (MRI): Brain imaging will be done via MRI prior to the first rTMS/Sham TMS session. Imaging will allow investigators to target specific areas in the brain.
Sham Transcranial Magnetic Stimulation
n=41 participants at risk
Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex. Sham Transcranial Magnetic Stimulation: Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation to the left motor cortex due to the use of a double sided Active/Sham coil used specifically for research studies. Magnetic resonance imaging (MRI): Brain imaging will be done via MRI prior to the first rTMS/Sham TMS session. Imaging will allow investigators to target specific areas in the brain.
General disorders
Vasovagal Response during study intervention
0.00%
0/38 • Up to 5 years
2.4%
1/41 • Number of events 1 • Up to 5 years
General disorders
Increased sensitivity to light w/ nausea
2.6%
1/38 • Number of events 1 • Up to 5 years
0.00%
0/41 • Up to 5 years
Reproductive system and breast disorders
Breast Cancer
0.00%
0/38 • Up to 5 years
2.4%
1/41 • Number of events 1 • Up to 5 years

Other adverse events

Adverse event data not reported

Additional Information

Dr. Albert Leung

VAORD

Phone: 858-552-8585

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place