Combined Transcranial Magnetic Stimulation and Therapy for mTBI Related Headaches

Combined Nonpharmacological Therapies for MTBI-Related Headaches

This study will assess the combined effectiveness of repetitive transcranial magnetic stimulation (rTMS) and telehealth based therapy in helping manage mild traumatic brain injury (mTBI) related headaches. The investigators hypothesize that active rTMS combined with telehealth therapy will provide marked reduction in mTBI related headaches and symptoms in comparison to their placebo counterparts.

Study Overview

• Status: Recruiting
• Conditions: Depression; TBI (Traumatic Brain Injury); Headache
• Intervention / Treatment: Device: Active rTMS; Behavioral: Headache Management Therapy; Behavioral: Headache Education Control; Device: Sham rTMS

Detailed Description

This study will be enrolling a total of 240 veterans or active military over a 4 year period at the VA San Diego Healthcare System (VASDHS). Participants will be randomized into one of four groups:

Group A: active rTMS with telehealth headache management therapy Group B: active rTMS with telehealth headache education control Group C: sham rTMS with telehealth headache management therapy Group D: sham rTMS with telehealth headache education control

Individual participation will consist of 19 visits to the VASDHS and 11 telehealth sessions over the course of 6-7 months. The in person visits will be divided into the following phases:

1. PRE-TREATMENT ASSESSMENTS PHASE (weeks 1-2) which consists of Visit 1 (Screening Visit) and Visit 2 (Baseline Assessments with MRI scan);
2. INDUCTION TREATMENT PHASE (weeks 3-4) consists of Visits 3-12 (10 weekday neuronavigation guided rTMS sessions at >24 and <72 hours apart); and
3. POST-TREATMENT ASSESSMENTS AND MAINTENANCE TREATMENT PHASE (weeks 5-24) consists of 4 initial biweekly post-induction treatment assessments and maintenance treatments (Visits 13-16)) and two additional monthly post-induction assessments and maintenance treatments (Visits 17-18) and one final study visit (Visit 19).

Eight weekly telehealth therapy/education sessions will be conducted from week 3 to 10 with additional three bolster sessions at 4 weeks apart. During the baseline and follow up visits, assessments will be conducted to evaluate headaches, neurobehavioral symptoms, depressive symptoms, post-concussion symptoms, and quality of life.

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Caleb Lopez, BS; Phone Number: 2638 858-552-8585; Email: caleb.lopez@va.gov

Study Locations

• United States
  • California
    • San Diego, California, United States, 92161
      • Recruiting
      • VA San Diego Healthcare System
      • Principal Investigator: Albert Y Leung, MD
      • Contact: Caleb Lopez, BS; Phone Number: 2638 858-552-8585; Email: caleb.lopez@va.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Mild Traumatic Brain Injury (mTBI)
2. Chronic headaches > 3 months after injury
3. Aged 18-65
4. No prior TMS treatment
5. Persistent Headaches with an intensity > 30 / 100
6. No history of daily headache prior to mTBI

Exclusion Criteria:

1. Pregnant
2. Pacemaker or any metal in body that would prevent MRI
3. History of dementia or major psychiatric disease, such as bipolar disorder or schizophrenia
4. Presence of any other chronic neuropathic pain states
5. History of seizure
6. Pending litigation
7. Can't understand English
8. History of chronic headache like migraine prior to mTBI
9. Evidence in chart of exacerbation of depressive/anxiety symptoms, active substance dependence, suicidal intent or attempt within previous month

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active rTMS with telehealth headache management therapy; Participants receive both active rTMS treatment at the left dorsolateral prefrontal cortex and therapy for headache management	Device: Active rTMS; Active rTMS will be given at the left dorsolateral prefrontal cortex with a double blind TMS coil.; Behavioral: Headache Management Therapy; Therapy will be provided on headache management.
Other: Active rTMS with telehealth headache education control; Participants receive active rTMS treatment at the left dorsolateral prefrontal cortex and headache education	Device: Active rTMS; Active rTMS will be given at the left dorsolateral prefrontal cortex with a double blind TMS coil.; Behavioral: Headache Education Control; In the control, educational sessions on headaches will be provided.
Other: Sham rTMS with telehealth headache management therapy; Participants receive sham rTMS treatment at the left dorsolateral prefrontal cortex and therapy for headache management	Behavioral: Headache Management Therapy; Therapy will be provided on headache management.; Device: Sham rTMS; Sham rTMS will be given at the left dorsolateral prefrontal cortex. All parameters of the treatment will appear identical to the active treatment, with only the rTMS coil used to administer the treatment flipped 180 degrees to prevent stimulation.
Sham Comparator: Sham rTMS with telehealth headache education control; Participants receive sham rTMS treatment at the left dorsolateral prefrontal cortex and headache education	Behavioral: Headache Education Control; In the control, educational sessions on headaches will be provided.; Device: Sham rTMS; Sham rTMS will be given at the left dorsolateral prefrontal cortex. All parameters of the treatment will appear identical to the active treatment, with only the rTMS coil used to administer the treatment flipped 180 degrees to prevent stimulation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intensity of Persistent Headaches	Assesses the intensity of persistent headaches, from a scale of 0, being no pain, to 10, being worst possible pain.	Change from baseline to 2-, 4-, 6-, 8-, 12-, 16-, and 20-weeks follow up visit
Intensity of Debilitating Headaches	Assesses the intensity of debilitating headaches, from a scale of 0, being no pain, to 10, being worst possible pain.	Change from baseline to 2-, 4-, 6-, 8-, 12-, 16-, and 20-weeks follow up visit
Persistent Headache Frequency	Assesses the frequency per week of persistent headaches	Change from baseline to 2-, 4-, 6-, 8-, 12-, 16-, and 20-weeks follow up visit
Debilitating Headache Frequency	Assesses the frequency per week of debilitating headaches	Change from baseline to 2-, 4-, 6-, 8-, 12-, 16-, and 20-weeks follow up visit
Debilitating Headache Interference	Assesses the interference of debilitating headaches for activities of daily living, from 0, being no interference, to 10, being worst possible interference.	Change from baseline to 2-, 4-, 6-, 8-, 12-, 16-, and 20-weeks follow up visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Headache Impact Test	Measures the impact of headache on an individual's ability to function at work, school, home, and/or social situations. Each item is measured from never, rarely, sometimes, very often, or always, with scores of 6, 8, 10, 11, and 13 respectively. A higher score correlates to a greater negative impact of headaches on quality of life.	Change from baseline to 2-, 4-, 6-, 8-, 12-, 16-, and 20-weeks follow up visit
Neurobehavioral Symptom Inventory	Assesses the severity of symptoms in the following areas: somatic, cognitive, affective, and sensory. Each item ranges from 0-4 with a higher score indicating a worse outcome.	Change from baseline to 2-, 4-, 6-, 8-, 12-, 16-, and 20-weeks follow up visit
Hamilton Rating Scale for Depression	Rates the severity of symptoms observed in depression such as low mood, insomnia, agitation, anxiety and weight loss. Scores range from 0 to 53, with a higher score indicating a larger degree of depression.	Change from baseline to 2-, 4-, 6-, 8-, 12-, 16-, and 20-weeks follow up visit
Rivermead Post-Concussion Symptoms Questionnaire	Assesses somatic, cognitive, and emotional symptoms experiences after traumatic brain injury. Each item ranges from 0-4, with a higher score indicating a worse outcome.	Change from baseline to 2-, 4-, 6-, 8-, 12-, 16-, and 20-weeks follow up visit
Short Form Health Survey-36	Measures health status and quality of life in regards to eight main areas: vitality, physical functioning, bodily pain, health perceptions, physical, emotional, and social role functioning and mental health. Each item is scored on a 0 to 100 range, with a higher score indicating a worse outcome.	Change from baseline to 2-, 4-, 6-, 8-, 12-, 16-, and 20-weeks follow up visit
Short-Form NEURO-QoL	Assesses quality of life related to neurological disorders. Each item ranges from 1-5, with a higher score indicating a worse outcome.	Change from baseline to 2-, 4-, 6-, 8-, 12-, 16-, and 20-weeks follow up visit

Collaborators and Investigators

• Sponsor: Veterans Medical Research Foundation
• Investigators: Principal Investigator: Albert Y Leung, MD, San Diego Veterans Healthcare System

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Estimated): August 31, 2025
• Study Completion (Estimated): August 31, 2025

Study Registration Dates

• First Submitted: November 24, 2021
• First Submitted That Met QC Criteria: December 14, 2021
• First Posted (Actual): January 4, 2022

Study Record Updates

• Last Update Posted (Actual): August 9, 2023
• Last Update Submitted That Met QC Criteria: August 7, 2023
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: rTMS; therapy; transcranial magnetic stimulation
• 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: CP200229; W81XWH2110831 (Other Grant/Funding Number: Department of Defense); H210076 (Other Identifier: VA San Diego Healthcare System)

Drug and device information, study documents

• 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