TBI (Traumatic Brain Injury)
Conditions
Brief summary
Due to recent wars in Afghanistan and Iraq, the number of Veteran suffering from Mild traumatic brain(MTBI) injury and PTSD increases rapidly. Headache is one of the most debilitating clinical symptoms in Veteran with MTBI and the cause of it is still not entirely clear. Recently, the use of non-invasive brain stimulation such as repetitive transcranial magnetic stimulation(rTMS) has yielded favorable clinical outcome in a few intractable chronic central pain conditions including headaches. This study aims to 1) assess the effect of rTMS in relieving headache and improving neurophysiological functions; and 2)explore the neuronal mechanisms associated with MTBI related headache and the analgesic effect of rTMS with function magnetic resonance imaging (fMRI).
Detailed description
This study will only be conducted at the Veterans Affair hospital in San Diego.
Interventions
DEVICETranscranial Magnetic Stimulation
Active-repetitive transcranial magnetic stimulation (rTMS) at the dorsal lateral prefrontal cortex.
DEVICESham Transcranial Magnetic Stimulation
Sham rTMS will consist of the same parameters as active, however, the subject will be shielded from the magnetic field of the coil.
Sponsors
United States Naval Medical Center, San Diego
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Male or female age between 18 to 50 * History of MTBI based on the clinical diagnostic criteria * History of headache more than 3 months * No prior experience of TMS treatment * Pre-treatment headache intensity M-VAS 30(0-100 scale) and average daily headache NPS 3(0-10 scale) * At least one headache exacerbation per day * A normal brain MRI in the past 3 months
Exclusion criteria
* Pregnancy * History of pacemaker implant * Any ferromagnetic(e.g. bullet fragment, shrapnel, device implant) in the brain or body that will prohibit the patients from having a brain MRI * History of dementia, major psychiatric diseases, or life threatening diseases * Presence of any other chronic neuropathic pain states * History of seizure * Pending litigation * Lack of ability to understand the experimental protocol and to adequately communicate in English * History of chronic headache prior to the incidence of MTBI
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Composite Score of Debilitating Headache (Intensity x Duration x Frequency) | Subjects will have a total of 9 visits over the span of 3 months, the baseline, 1-week follow-up and 1-month follow up will qualify as a time point at which the outcome is measured and averaged. | The primary outcome time-point measurement will be averaged from each day the subject is enrolled in the study for each of the 3 time point periods: pre-treatment baseline, 1-week follow-up and 1-month follow-up. The results depict change in the composite score: intensity (scale of 0-10) x duration (# of hours) x frequency (# headaches per week). The larger composite score for each subject, the worse the debilitating headaches. |
| Percent Change in Persistent Headache Intensity | Subjects will have a total of 9 visits over the span of 3 months, the baseline, 1-week follow-up and 1-month follow up will qualify as a time point at which the outcome is measured and averaged. | The persistent headache measure was assessed through a daily headache log over the course of the subjects participation in the study and averaged for the time point period of baseline, 1-week and 1-month results. The persistent headache is based on a scale of 0-10, the higher the persistent headache intensity averaged score the worse the persistent headache. |
| Percent Change in Persistent Headache Prevalence | Subjects will have a total of 9 visits over the span of 3 months, the baseline, 1-week follow-up and 1-month follow up will qualify as a time point at which the outcome is measured. | The persistent headache prevalence measure was assessed through a daily headache log over the course of the subjects participation in the study and collected at baseline, 1-week and 1-month. The persistent headache is defined as having had 3+ continuous headaches over the course of the time point periods and was coded as either yes or no. The results indicate the percent change in the prevalence of persistent headaches for the subjects at the time points. A larger reduction percent indicates a larger decrease in subjects with those persistent headaches. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Depression Score From Baseline to 1-Week Post-treatment | Subjects will have a total of 9 visits over the span of 3 months and 3 of those visits will qualify as a time point at which outcome is measured. | Subjects assessed how their headaches interfered with their mood through the Hamilton Rating Scale for Depression assessment at baseline, 1-week follow-up and 1-month follow-up. The outcome was measured by adding the score of each question on the assessment and then comparing the averaged scores at the different time points. The larger the depression score, the more severe the depression. A larger percent change in depression score indicates a change in the severity of the depression. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Transcranial Magnetic Stimulation Active-repetitive transcranial magnetic stimulation (rTMS) at the dorsal lateral prefrontal cortex.
Transcranial Magnetic Stimulation: Active-repetitive transcranial magnetic stimulation (rTMS) at the dorsal lateral prefrontal cortex. | 14 |
| Sham Transcranial Magnetic Stimulation Sham rTMS will consist of the same parameters as active, however, the subject will be shielded from the magnetic field of the coil.
Sham Transcranial Magnetic Stimulation: Sham rTMS will consist of the same parameters as active, however, the subject will be shielded from the magnetic field of the coil. | 15 |
| Total | 29 |
Baseline characteristics
| Characteristic | Transcranial Magnetic Stimulation | Sham Transcranial Magnetic Stimulation | Total |
|---|---|---|---|
| Age, Continuous | 36.13 years STANDARD_DEVIATION 9.39 | 34.43 years STANDARD_DEVIATION 7.66 | 35.28 years STANDARD_DEVIATION 8.52 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 4 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 6 Participants | 10 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 5 Participants | 12 Participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 6 Participants |
| Sex: Female, Male Male | 12 Participants | 11 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 15 |
| other Total, other adverse events | 0 / 14 | 0 / 15 |
| serious Total, serious adverse events | 0 / 14 | 0 / 15 |
Outcome results
Primary
Percent Change in Composite Score of Debilitating Headache (Intensity x Duration x Frequency)
The primary outcome time-point measurement will be averaged from each day the subject is enrolled in the study for each of the 3 time point periods: pre-treatment baseline, 1-week follow-up and 1-month follow-up. The results depict change in the composite score: intensity (scale of 0-10) x duration (# of hours) x frequency (# headaches per week). The larger composite score for each subject, the worse the debilitating headaches.
Time frame: Subjects will have a total of 9 visits over the span of 3 months, the baseline, 1-week follow-up and 1-month follow up will qualify as a time point at which the outcome is measured and averaged.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Transcranial Magnetic Stimulation | Percent Change in Composite Score of Debilitating Headache (Intensity x Duration x Frequency) | 1-Week Follow-Up | -55.3 percent change from baseline | Standard Deviation 29 |
| Transcranial Magnetic Stimulation | Percent Change in Composite Score of Debilitating Headache (Intensity x Duration x Frequency) | 1-Month Follow-Up | -58.4 percent change from baseline | Standard Deviation 24.4 |
| Sham Transcranial Magnetic Stimulation | Percent Change in Composite Score of Debilitating Headache (Intensity x Duration x Frequency) | 1-Week Follow-Up | -1.7 percent change from baseline | Standard Deviation 41.2 |
| Sham Transcranial Magnetic Stimulation | Percent Change in Composite Score of Debilitating Headache (Intensity x Duration x Frequency) | 1-Month Follow-Up | -10 percent change from baseline | Standard Deviation 59.9 |
Comparison: Change from Baseline to 1-Week Post-Treatmentp-value: <0.0001ANOVA
Comparison: Change from Baseline to 1-Month Post-Treatmentp-value: <0.001ANOVA
Primary
Percent Change in Persistent Headache Intensity
The persistent headache measure was assessed through a daily headache log over the course of the subjects participation in the study and averaged for the time point period of baseline, 1-week and 1-month results. The persistent headache is based on a scale of 0-10, the higher the persistent headache intensity averaged score the worse the persistent headache.
Time frame: Subjects will have a total of 9 visits over the span of 3 months, the baseline, 1-week follow-up and 1-month follow up will qualify as a time point at which the outcome is measured and averaged.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Transcranial Magnetic Stimulation | Percent Change in Persistent Headache Intensity | 1-Week Follow-Up | -25.3 percent change from baseline | Standard Deviation 16.8 |
| Transcranial Magnetic Stimulation | Percent Change in Persistent Headache Intensity | 1-Month Follow-Up | -22.6 percent change from baseline | Standard Deviation 17.7 |
| Sham Transcranial Magnetic Stimulation | Percent Change in Persistent Headache Intensity | 1-Week Follow-Up | -1.0 percent change from baseline | Standard Deviation 11.7 |
| Sham Transcranial Magnetic Stimulation | Percent Change in Persistent Headache Intensity | 1-Month Follow-Up | -2.3 percent change from baseline | Standard Deviation 14.5 |
p-value: <0.001ANOVA
p-value: <0.01ANOVA
Primary
Percent Change in Persistent Headache Prevalence
The persistent headache prevalence measure was assessed through a daily headache log over the course of the subjects participation in the study and collected at baseline, 1-week and 1-month. The persistent headache is defined as having had 3+ continuous headaches over the course of the time point periods and was coded as either yes or no. The results indicate the percent change in the prevalence of persistent headaches for the subjects at the time points. A larger reduction percent indicates a larger decrease in subjects with those persistent headaches.
Time frame: Subjects will have a total of 9 visits over the span of 3 months, the baseline, 1-week follow-up and 1-month follow up will qualify as a time point at which the outcome is measured.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Transcranial Magnetic Stimulation | Percent Change in Persistent Headache Prevalence | 1-Week Follow-Up | -50 percent change from baseline | Standard Deviation 51 |
| Transcranial Magnetic Stimulation | Percent Change in Persistent Headache Prevalence | 1-Month Follow-Up | -57 percent change from baseline | Standard Deviation 52 |
| Sham Transcranial Magnetic Stimulation | Percent Change in Persistent Headache Prevalence | 1-Week Follow-Up | -7 percent change from baseline | Standard Deviation 26 |
| Sham Transcranial Magnetic Stimulation | Percent Change in Persistent Headache Prevalence | 1-Month Follow-Up | -20 percent change from baseline | Standard Deviation 41 |
p-value: 0.009ANOVA
p-value: <0.01ANOVA
Secondary
Percent Change in Depression Score From Baseline to 1-Week Post-treatment
Subjects assessed how their headaches interfered with their mood through the Hamilton Rating Scale for Depression assessment at baseline, 1-week follow-up and 1-month follow-up. The outcome was measured by adding the score of each question on the assessment and then comparing the averaged scores at the different time points. The larger the depression score, the more severe the depression. A larger percent change in depression score indicates a change in the severity of the depression.
Time frame: Subjects will have a total of 9 visits over the span of 3 months and 3 of those visits will qualify as a time point at which outcome is measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Transcranial Magnetic Stimulation | Percent Change in Depression Score From Baseline to 1-Week Post-treatment | -14.8 percent change in score from baseline | Standard Deviation 22.1 |
| Sham Transcranial Magnetic Stimulation | Percent Change in Depression Score From Baseline to 1-Week Post-treatment | -2.7 percent change in score from baseline | Standard Deviation 40.3 |
p-value: =0.033ANOVA