Improving Functions in MTBI Patients With Headache by rTMS

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).

Study Overview

• Status: Completed
• Conditions: TBI (Traumatic Brain Injury)
• Intervention / Treatment: Device: Transcranial Magnetic Stimulation; Device: Sham Transcranial Magnetic Stimulation

Detailed Description

This study will only be conducted at the Veterans Affair hospital in San Diego.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92161
      • VA San Diego Healthcare System, San Diego, CA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Transcranial Magnetic Stimulation; Active-repetitive transcranial magnetic stimulation (rTMS) at the dorsal lateral prefrontal cortex.	Device: Transcranial Magnetic Stimulation; Active-repetitive transcranial magnetic stimulation (rTMS) at the dorsal lateral prefrontal cortex.
Sham Comparator: 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.	Device: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.
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.	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.
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.	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.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Collaborators: United States Naval Medical Center, San Diego
• Investigators: Principal Investigator: Albert Y Leung, MD, VA San Diego Healthcare System, San Diego, CA

Publications and helpful links

General Publications

• Vaninetti M, Lim M, Khalaf A, Metzger-Smith V, Flowers M, Kunnel A, Yang E, Song D, Lin L, Tsai A, Lee R, Golshan S, Leung A. fMRI findings in MTBI patients with headaches following rTMS. Sci Rep. 2021 May 5;11(1):9573. doi: 10.1038/s41598-021-89118-2.

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: September 17, 2013
• First Submitted That Met QC Criteria: September 19, 2013
• First Posted (Estimate): September 24, 2013

Study Record Updates

• Last Update Posted (Actual): March 26, 2018
• Last Update Submitted That Met QC Criteria: February 23, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Brain Injuries, Traumatic; Headache
• Other Study ID Numbers: F1359-P; H130281 SPiRE rTMS MTBI HA (Other Identifier: San Diego VA Healthcare System)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO