Back to resultsManaging MTBI-related Headaches With rTMS
Primary Purpose
Traumatic Brain Injury (TBI)
Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Transcranial Magnetic Stimulation
Sham Transcranial Magnetic Stimulation
Sponsored by
About this trial
This is an interventional treatment trial for Traumatic Brain Injury (TBI) focused on measuring TBI, traumatic brain injury, transcranial magnetic stimulation, headache
Eligibility Criteria
Inclusion Criteria:
- The following diagnostic criteria for MTBI based on the 1993 American Congress of Rehabilitation Medicine and recent recommendation from the DOD, and the current diagnostic criteria adopted by the VASDHS TBI Clinic will be used for the study. A traumatically induced physiological disruption of brain function, as manifested by at least one of the following:
- any loss of consciousness
- any loss of memory for events immediately before or after the accident
any alteration in mental state at the time of the accident, e.g.:
- feeling dazed
- disoriented
- confused)
Focal neurologic deficit (s) that may or may not be transient but where the severity of the injury does not exceed the following:
- loss of consciousness of approximately 30 min or less
- after 30 min, an initial Glasgow Coma Scale score of 13-15
- post-traumatic amnesia not greater than 24 hrs
In addition, the following established diagnostic criteria for " Persistent headache attributed to mild traumatic injury headache" based on the International Classification of Headache Disorder (ICHD-3) will be applied to the study subjects:
- A. Any headache fulfilling criteria C and D
- B. Traumatic injury to the head has occurred
- C. Headache is reported to have developed within 7 d after one of the following:
- 1. injury to the head
- 2. regaining of consciousness following the injury
- 3. discontinuation of medication(s) that impairs the ability to sense or report headache following the injury
- D. Headache persists for >3 mo after injury to the head
- E. Not better accounted for by another ICHD-3 diagnosis
Additional Inclusion Criteria:
- no prior experience of TMS treatment
- average persistent headache intensity more than 30 on the 0-100 mechanical visual analog scale(M-VAS) at the screening visit (visit 1) and average persistent headache intensity score greater than 3/10 on a numerical rating scale (NRS) reported in the headache diary (between visits 1&2)
- no history of daily persistent headache prior to the MTBI incidence
Exclusion Criteria:
- pregnancy; To be eligible for the study and to ensure no pregnancy risk, you will need to utilize contraception or practice abstinence until your study participation is completed
- history of pacemaker implant
any ferromagnetic material in the brain or body that would prohibit the patients from having a brain MRI, e.g.:
- bullet fragment
- shrapnel
- device implant
- history of dementia, major psychiatric 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 diagnoses such migraine, tension or cluster headaches prior to the incidence of MTBI.
- history of chronic headache prior to the MTBI incidence at a frequency more than once a month lasting more than one hour.
- evidence in the chart of recent exacerbation of depressive or anxiety symptoms, active substance dependence, suicidal intent or attempt within the previous month, and/or current psychotic symptoms
Sites / Locations
- VA San Diego Healthcare System, San Diego, CA
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Sham Comparator
Arm Label
Transcranial Magnetic Stimulation
Sham Transcranial Magnetic Stimulation
Arm Description
Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex.
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.
Outcomes
Primary Outcome Measures
Reduce the intensity, frequency and duration of MTBI-headaches
The outcome measure will be quantified through the headache diary log that tracks the intensity, frequency and duration of MTBI-headaches (MTBI-HA)
Change from Baseline to Post-Treatment Quality of Life scores
The outcome measure will be quantified through the self-assessed short form impact on quality of life (SF-36). The SF-36 has eight scaled scores; the scores are weighted sums of the questions in each section. Scores range from 0 - 100 where Lower scores = more disability and higher scores = less disability The sections include: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning and mental health.
Change from Baseline to Post-Treatment Depression scores
The outcome measure 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.
Change in attention scores from Baseline to Post-Treatment visits
The outcome measure will be quantified through the Connors continuous performance test for sustained and selective attention. This is administered on a laptop and is automatically scored.
Change from Baseline to Post-Treatment Global Pain scores.
The outcome measure will be quantified through the self-assessed global pain inventory survey. 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. 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 added together for an overall Global Pain score.
Change from Baseline to Post-Treatment Post Traumatic Stress Disorder (PTSD) scores
The outcome measure will be quantified through the administered CAPS, a structured interview designed to make a categorical PTSD diagnosis, as well as to provide a measure of PTSD symptom severity. The symptoms are rated for both frequency and intensity; these two scores are summed to provide severity ratings.
Change from Baseline to Post-Treatment memory scores
The outcome measure will be quantified through the Hopkins Verbal Learning Test (HVLT-R) for memory. When scoring the HVLT-R, the three learning trials are combined to calculate a total recall score and the delayed recall trial creates the delayed recall score.
Change from Baseline to Post-Treatment Executive Functioning
The outcome measure will be quantified through the Trail Making Test A and B and Stroop Test for executive functioning. The Trail Making Test consists of two parts in which the subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy. And the Stroop Test is a demonstration of interference in the reaction time of a task.
Secondary Outcome Measures
Explore the treatment effect on the pain related network of the brain
The outcome measure will be assessed through functional magnetic imaging scans and subsequent processing.
Full Information
NCT ID
NCT03314584
First Posted
October 4, 2017
Last Updated
October 4, 2023
Sponsor
VA Office of Research and Development
1. Study Identification
Unique Protocol Identification Number
NCT03314584
Brief Title
Managing MTBI-related Headaches With rTMS
Official Title
Long Term Efficacy of rTMS in Managing MTBI-related Headache
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 1, 2018 (Actual)
Primary Completion Date
September 30, 2023 (Actual)
Study Completion Date
November 30, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
VA Office of Research and Development
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Persistent headache is one of the most common debilitating symptoms in military personnel suffering from mild traumatic brain injury (MTBI). This study aims to assess the long-term effect of repetitive transcranial magnetic stimulation (rTMS) in managing MTBI related headaches for up to 2-3 months by comparing the treatment effect of active-rTMS to sham-rTMS.
Detailed Description
Headache is one of the most common debilitating chronic pain conditions in either active or retired military personnel with MTBI. This high prevalence of persistent chronic headache is often associated with neuropsychological dysfunction in mood, attention, and memory, which casts a profound negative impact on patients' quality of life and increases stress in their caregivers. Unfortunately, as witnessed by the investigators in their clinical practices, conventional pharmacological treatments for MTBI related headache (MTBI-HA) has not been shown to be effective and drugs such as narcotics contain many long-term untoward psychosomatic and abusive side effects. This calls for an urgent need in developing alternate and innovative long-term headache management strategies for this rapidly increasing patient population.
Coinciding with other published treatment protocols related to traumatic brain injury and pain, this initial clinical evidence provides compelling support for the current proposal aiming to assess the effect of a longer duration of rTMS protocol in managing MTBI-HA for up to 10 weeks after the initiation of the treatment. Given existing treatment options for MTBI-HA are limited, validating such a non-pharmacological and non-invasive treatment option will significantly enhance the capability of the VA healthcare system in caring for this rapidly increasing patient population.
PRE-TREATMENT PHASE (weeks 1-2) consists of Visit 1 (Screening Visit) and Visit 2 (Pre-treatment Assessments);
TREAMENT PHASE (week 3-4) consists of Visits 3-12 (Neuronagvigation guided rTMS consisting of 10 weekday treatments at >24 and < 72 hours apart, weekends excluded, maximum 5 weeks for treatment completion) rTMS will take place in Building 23 Room 105 at the VASDHS; and
POST-TREATMENT PHASE (week 5-14) consists of two initial weekly visits (Visits 13&14) and two additional biweekly visits (Visits 15&16) and one monthly visit (Visit 17).
Brain anatomical and functional MRI will be performed within 72 hours after Visits 2 and 13. Subjects will be required to fill out headache diary between assessment visits. Headache assessments along with quality of life, mood and functions assessments will be carried out at Visits 1,2, and 13--17. This frequency of treatment and duration of follow-up is in line with recently published rTMS articles related to TBI, headache and pain, and also in accordance with the 3-month post treatment initiation follow-up guideline/recommendation [32; 55; 80].
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Traumatic Brain Injury (TBI)
Keywords
TBI, traumatic brain injury, transcranial magnetic stimulation, headache
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Masking Description
This is a double-blinded study where only the statistician is aware of the randomization.
Allocation
Randomized
Enrollment
179 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Transcranial Magnetic Stimulation
Arm Type
Experimental
Arm Description
Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex.
Arm Title
Sham Transcranial Magnetic Stimulation
Arm Type
Sham Comparator
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
Transcranial Magnetic Stimulation
Intervention Description
Active-repetitive transcranial magnetic stimulation (rTMS) at the left motor cortex.
Intervention Type
Device
Intervention Name(s)
Sham Transcranial Magnetic Stimulation
Intervention Description
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.
Primary Outcome Measure Information:
Title
Reduce the intensity, frequency and duration of MTBI-headaches
Description
The outcome measure will be quantified through the headache diary log that tracks the intensity, frequency and duration of MTBI-headaches (MTBI-HA)
Time Frame
The measure will be assessed daily from baseline to the 3-month post-treatment follow up visit.
Title
Change from Baseline to Post-Treatment Quality of Life scores
Description
The outcome measure will be quantified through the self-assessed short form impact on quality of life (SF-36). The SF-36 has eight scaled scores; the scores are weighted sums of the questions in each section. Scores range from 0 - 100 where Lower scores = more disability and higher scores = less disability The sections include: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning and mental health.
Time Frame
The measure will be assessed at the Baseline visit, 1-Week, 1-Month, 2-Month and 3-month post-treatment follow up visits.
Title
Change from Baseline to Post-Treatment Depression scores
Description
The outcome measure 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.
Time Frame
The measure will be assessed at the Baseline visit, 1-Week, 1-Month, 2-Month and 3-month post-treatment follow up visits.
Title
Change in attention scores from Baseline to Post-Treatment visits
Description
The outcome measure will be quantified through the Connors continuous performance test for sustained and selective attention. This is administered on a laptop and is automatically scored.
Time Frame
The measure will be assessed at the Baseline visit, 1-Week, 1-Month, 2-Month and 3-month post-treatment follow up visits.
Title
Change from Baseline to Post-Treatment Global Pain scores.
Description
The outcome measure will be quantified through the self-assessed global pain inventory survey. 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. 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 added together for an overall Global Pain score.
Time Frame
The measure will be assessed at the Baseline visit, 1-Week, 1-Month, 2-Month and 3-month post-treatment follow up visits.
Title
Change from Baseline to Post-Treatment Post Traumatic Stress Disorder (PTSD) scores
Description
The outcome measure will be quantified through the administered CAPS, a structured interview designed to make a categorical PTSD diagnosis, as well as to provide a measure of PTSD symptom severity. The symptoms are rated for both frequency and intensity; these two scores are summed to provide severity ratings.
Time Frame
The measure will be assessed at the Baseline visit, 1-Month, 2-Month and 3-month post-treatment follow up visits.
Title
Change from Baseline to Post-Treatment memory scores
Description
The outcome measure will be quantified through the Hopkins Verbal Learning Test (HVLT-R) for memory. When scoring the HVLT-R, the three learning trials are combined to calculate a total recall score and the delayed recall trial creates the delayed recall score.
Time Frame
The measure will be assessed at the Baseline visit, 1-Week, 1-Month, 2-Month and 3-month post-treatment follow up visits.
Title
Change from Baseline to Post-Treatment Executive Functioning
Description
The outcome measure will be quantified through the Trail Making Test A and B and Stroop Test for executive functioning. The Trail Making Test consists of two parts in which the subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy. And the Stroop Test is a demonstration of interference in the reaction time of a task.
Time Frame
The measure will be assessed at the Baseline visit, 1-Week, 1-Month, 2-Month and 3-month post-treatment follow up visits.
Secondary Outcome Measure Information:
Title
Explore the treatment effect on the pain related network of the brain
Description
The outcome measure will be assessed through functional magnetic imaging scans and subsequent processing.
Time Frame
Subjects will have 2 functional magnetic imaging scans, at baseline and then at the 1-week post treatment follow-up.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
The following diagnostic criteria for MTBI based on the 1993 American Congress of Rehabilitation Medicine and recent recommendation from the DOD, and the current diagnostic criteria adopted by the VASDHS TBI Clinic will be used for the study. A traumatically induced physiological disruption of brain function, as manifested by at least one of the following:
any loss of consciousness
any loss of memory for events immediately before or after the accident
any alteration in mental state at the time of the accident, e.g.:
feeling dazed
disoriented
confused)
Focal neurologic deficit (s) that may or may not be transient but where the severity of the injury does not exceed the following:
loss of consciousness of approximately 30 min or less
after 30 min, an initial Glasgow Coma Scale score of 13-15
post-traumatic amnesia not greater than 24 hrs
In addition, the following established diagnostic criteria for " Persistent headache attributed to mild traumatic injury headache" based on the International Classification of Headache Disorder (ICHD-3) will be applied to the study subjects:
A. Any headache fulfilling criteria C and D
B. Traumatic injury to the head has occurred
C. Headache is reported to have developed within 7 d after one of the following:
1. injury to the head
2. regaining of consciousness following the injury
3. discontinuation of medication(s) that impairs the ability to sense or report headache following the injury
D. Headache persists for >3 mo after injury to the head
E. Not better accounted for by another ICHD-3 diagnosis
Additional Inclusion Criteria:
no prior experience of TMS treatment
average persistent headache intensity more than 30 on the 0-100 mechanical visual analog scale(M-VAS) at the screening visit (visit 1) and average persistent headache intensity score greater than 3/10 on a numerical rating scale (NRS) reported in the headache diary (between visits 1&2)
no history of daily persistent headache prior to the MTBI incidence
Exclusion Criteria:
pregnancy; To be eligible for the study and to ensure no pregnancy risk, you will need to utilize contraception or practice abstinence until your study participation is completed
history of pacemaker implant
any ferromagnetic material in the brain or body that would prohibit the patients from having a brain MRI, e.g.:
bullet fragment
shrapnel
device implant
history of dementia, major psychiatric 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 diagnoses such migraine, tension or cluster headaches prior to the incidence of MTBI.
history of chronic headache prior to the MTBI incidence at a frequency more than once a month lasting more than one hour.
evidence in the chart of recent exacerbation of depressive or anxiety symptoms, active substance dependence, suicidal intent or attempt within the previous month, and/or current psychotic symptoms
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Albert Yick Leung, MD
Organizational Affiliation
VA San Diego Healthcare System, San Diego, CA
Official's Role
Principal Investigator
Facility Information:
Facility Name
VA San Diego Healthcare System, San Diego, CA
City
San Diego
State/Province
California
ZIP/Postal Code
92161-0002
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Managing MTBI-related Headaches With rTMS
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