Clinical trial NCT03314584: Managing Mild Traumatic Brain Injury Related Headaches With Repetitive Transcranial Magnetic Stimulation
Official title: Long Term Efficacy of rTMS in Managing MTBI-related Headache
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Traumatic Brain Injury (TBI)
Keywords: TBI
traumatic brain injury
transcranial magnetic stimulation
headache
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2017-10-19
Enrollment: 179
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

1. PRE-TREATMENT PHASE (weeks 1-2) consists of Visit 1 (Screening Visit) and Visit 2 (Pre-treatment Assessments);
2. TREAMENT PHASE (week 3-4) consists of Visits 3-12 (Neuronavigation 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
3. 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.

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

Primary outcomes:
measure: Reduce the intensity, frequency and duration of MTBI-headaches
timeFrame: The measure will be assessed daily from baseline to the 3-month post-treatment follow up visit.
measure: Change from Baseline to Post-Treatment Quality of Life scores
timeFrame: The measure will be assessed at the Baseline visit, 1-Week, 1-Month, 2-Month and 3-month post-treatment follow up visits.
measure: Change from Baseline to Post-Treatment Depression scores
timeFrame: The measure will be assessed at the Baseline visit, 1-Week, 1-Month, 2-Month and 3-month post-treatment follow up visits.
measure: Change in attention scores from Baseline to Post-Treatment visits
timeFrame: The measure will be assessed at the Baseline visit, 1-Week, 1-Month, 2-Month and 3-month post-treatment follow up visits.
measure: Change from Baseline to Post-Treatment Global Pain scores.
timeFrame: The measure will be assessed at the Baseline visit, 1-Week, 1-Month, 2-Month and 3-month post-treatment follow up visits.
measure: Change from Baseline to Post-Treatment Post Traumatic Stress Disorder (PTSD) scores
timeFrame: The measure will be assessed at the Baseline visit, 1-Month, 2-Month and 3-month post-treatment follow up visits.
measure: Change from Baseline to Post-Treatment memory scores
timeFrame: The measure will be assessed at the Baseline visit, 1-Week, 1-Month, 2-Month and 3-month post-treatment follow up visits.
measure: Change from Baseline to Post-Treatment Executive Functioning
timeFrame: The measure will be assessed at the Baseline visit, 1-Week, 1-Month, 2-Month and 3-month post-treatment follow up visits.
Secondary outcomes:
measure: Explore the treatment effect on the pain related network of the brain
timeFrame: Subjects will have 2 functional magnetic imaging scans, at baseline and then at the 1-week post treatment follow-up.
Other outcomes:
Locations:
city: San Diego
country: United States
facility: VA San Diego Healthcare System, San Diego, CA
state: California
Study officials:
affiliation: VA San Diego Healthcare System, San Diego, CA
name: Albert Yick Leung, MD
role: PRINCIPAL_INVESTIGATOR
References: