Ignite Creation Date:
2024-05-06 @ 3:13 PM
Last Modification Date:
2024-10-26 @ 1:45 PM
Study NCT ID:
NCT04568369
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2023-11-24
First Post:
2020-09-04
Brief Title:
Treatment of Post-concussion Syndrome With TMS Using FNIRS as a Biomarker of Response
Sponsor:
University of Calgary
Organization:
University of Calgary
Study Overview
Official Title:
Functional Near Infrared Spectroscopy as a Biomarker of Response in Patients With Post-concussion Syndrome Treated With Transcranial Magnetic Stimulation
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2023-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Every year approximately 2 million people in the United States and 280000 in Canada experience a mild traumatic brain injuryconcussion In patients with concussion symptoms experienced following injury usually get better within 3 months However approximately 5-25 of people will experience symptoms beyond the 3 month period characterized by persistent headaches fatigue insomnia anxiety depression and thinking or concentration problems which contribute to significant functional impairment Chronic headache is the most common symptom following concussions They can last beyond 5 years following injury significantly impacting daily activities To date post-concussion symptoms have no known cure
One potential approach to treating post-concussion symptoms may involve using drug-free interventions such as neuromodulation therapy This has the goal of restoring normal brain activity Repetitive transcranial magnetic stimulation rTMS is one method currently being explored as a treatment option TMS is a procedure where brain electrical activity is influenced by a magnetic field Numerous studies using rTMS to treat other disorders such as dementia stroke cerebral palsy addictions depression and anxiety have shown much promise The primary objective of this study is to determine whether rTMS treatment can significantly improve persistent post-concussion symptoms A secondary objective is to explore the relationship between potential changes in brain function and clinical markers associated with rTMS treatment and how functional near-infrared spectroscopy fNIRS a neuroimaging technology may be used to assess rTMS-treatment response
One potential approach to treating post-concussion symptoms may involve using drug-free interventions such as neuromodulation therapy This has the goal of restoring normal brain activity Repetitive transcranial magnetic stimulation rTMS is one method currently being explored as a treatment option TMS is a procedure where brain electrical activity is influenced by a magnetic field Numerous studies using rTMS to treat other disorders such as dementia stroke cerebral palsy addictions depression and anxiety have shown much promise The primary objective of this study is to determine whether rTMS treatment can significantly improve persistent post-concussion symptoms A secondary objective is to explore the relationship between potential changes in brain function and clinical markers associated with rTMS treatment and how functional near-infrared spectroscopy fNIRS a neuroimaging technology may be used to assess rTMS-treatment response
Detailed Description:
Annually up to 280000 people in Canada and 42 million worldwide experience a mild traumatic brain injury mTBI In patients with mTBI symptoms experienced following injury usually resolve within 3 months However up to 25 of patients will experience persistent post-concussion symptoms PPCS which can continue up to 1 year following injury Common symptoms include headaches dizziness fatigue irritability depression anxiety emotional lability concentration or memory difficulties insomnia and reduced alcohol tolerance ICD-10 post-concussion syndrome diagnostic criteria To date there is no cure for PPCS and current treatment entails trial and error with behavior management environmental modifications and medications Consequently there is a significant need for new approaches to symptom management in order to help improve functional impairment and disease burden associated with PPCS Transcranial magnetic stimulation TMS has been studied as an intervention for many mental health and neurological conditions including major depression and migraines and has shown initial promise for PPCS We intend to study the efficacy of TMS for PPCS further in a randomized sham-controlled trial
Mild traumatic injury is considered a risk factor in the development of post-traumatic stress disorder As such post-traumatic stress disorder and mild traumatic brain injury often co-occur and share similar symptoms such as irritability post-traumatic amnesia sleep disturbances concentration difficulties and cognitive processing deficits Several studies have suggested the efficacy and safety of rTMS for the treatment of PTSD however a gap in the literature exists regarding treating comorbid post-traumatic stress disorder and PPCS following mild traumatic brain injury To study potential differences in response to treatment between individuals experiencing PPCS with or without co-morbid post-traumatic stress disorder we intend to measure PTSD symptoms for those with a clinical diagnosis of post-traumatic stress disorder Tracking PTSD symptoms will allow insight into whether the presence of PTSD symptoms affects rTMS treatment outcomes in individuals experiencing PPCS
RESEARCH QUESTIONS AND OBJECTIVES
The overall goal is to study the application of rTMS treatment to the left dorsal lateral prefrontal cortex DLPFC in patients with PPCS to improve overall symptom burden and to explore biomarkers of response specifically functional near infrared spectroscopy fNIRS
Specifically the objectives are
1 Primary Objective to determine changes in brain physiology associated with rTMS treatment as recorded by fNIRS
2 Secondary Objective to determine whether patients with PPCS have significant improvement to a 20-day high frequency rTMS treatment protocol of the left DLPFC compared to patients with PPCS receiving a sham rTMS protocol as measured by the Rivermead post-concussion symptom questionnaire at 1 and 3 months post-treatment
3 Third Objective To determine what exploratory outcomes such as quality of life headaches anxiety depression sleep and somatic symptoms also improve with TMS treatment in individuals suffering with PPCS Quality of life will be measured via the Quality of Life after Brain Injury questionnaire QOLIBRI headache intensity will be measured via the Headache intensity Test - 6 HIT-6 feelings of depression will be measured via the Patient Health Questionnaire -9 PHQ-9 anxiety via the Generalized Anxiety Disorder -7 GAD-7 sleep via the Sleep and Concussion Questionnaire and somatic symptoms which are commonly present in functional neurological disorders via the SOMS-CD and Patient Health Questionnaire-15 PHQ-15 Since Functional Neurological Disorder is often associated with past trauma trauma history will be assessed via the Brief Trauma Questionnaire BTQ and the Life Stress Questionnaire LSQ
4 To determine whether those with PPCS and PTSD respond differently to rTMS and what effect this has on their PTSD symptoms measured via the Clinician-Administered PTSD Scale for DSM-5 CAPS-5 and the Montgomery-Asberg Depression Rating Scale Participants with PTSD will be identified as those with scores higher than 33 in the PCL-5 and a clinical diagnosis of PTSD by a medical professional
5 To examine potential blood biomarkers of post-concussion syndrome and post-traumatic stress disorder
METHODS
This study will be a double-blind sham-controlled concealed allocation randomized clinical trial
Clinical Assessments Demographic information will be collected prior to starting the study including age sex education headache history concussion history past medical history medication use and family medical history Baseline questionnaires will be completed including Headache Impact Test - 6 HIT-6 Rivermead PPCS questionnaire British Columbia post-concussion symptom inventory BC-PSI quality of life after brain injury questionnaire QOLIBRI patient health questionnaire-9 PHQ-9 generalized anxiety disorder scale-7 GADS-7the St Louis University Mental examination Tool SLUMS the screening for somatoform symptoms questionnaire SOMS-CD the post traumatic stress disorder checklist for DSM-5 PCL-5 the Brief Trauma Questionniare BTQ the Life Stress Questionnaire LSQ the Patient Health Questionnaire-15 PHQ-15 and the Sleep and Concussion Questionnaire SCQ Those who are identified as having a PCL-5 score of greater than 33 in addition to a clinical diagnosis of post-traumatic stress disorder will also complete the LEC-5 CAPS-5 MADRS and Columbia Suicide Severity Rating Scale Patients will be reassessed at the completion of their rTMS treatment and at 1 and 3 months post-treatment The questionnaires that will be completed at all follow-up visits include the Rivermead PPCS questionnaire the HIT-6 the BC-PSI the QOLIBRI the PHQ-9 the GAD-7 the PCL-5 the SLUMS the SOMS-CD the PHQ-15 and the Sleep and Concussion Questionnaire For the Sleep and Concussion Questionnaire the initial screening section will not be completed at follow-ups Participants in the PTSD sub-group will also complete the MADRS CAPS-5 and Columbia Suicide Severity Rating Scale at the 1 month and 3-month follow-up visits
TMS Protocol Patients will engage in a four-week treatment protocol 20 treatments This was chosen as it is the midpoint between typical depression and migraine protocol durations A standardized atlas brain with Montreal Neurologic Institute MNI coordinates will be used for navigation The DLPFC will be located through MNI coordinates -50 30 36 The intensity of the rTMS will be 100-120 of resting motor threshold amplitude with a frequency of 10 Hz 10 trains of 60 pulsestrain total of 600 pulses and inter-train interval of 45s In the sham condition a sham coil will be applied to the scalp after the resting motor threshold is determined Patients will be able to hear the sound and feel the vibration of sham coil but will not experience any effective stimulation Previous sham studies have demonstrated efficacy of the blinding method
Imaging Functional near infrared spectroscopy fNIRS measurements will be recorded at baseline immediately following rTMS and at one month and 3-month follow-ups post-rTMS to investigate changes in brain physiology associated with rTMS treatment fNIRS data will be recorded over the frontoparietal cortex at a sampling rate of 391 Hz using the TechEn fNIRS system TechEn Inc Milford MA USA Each recording will consist of a 5 min rest period followed by a finger tapping exercise and a graded working memory task previously described by Hocke et al 2018 The fNIRS data will be processed and analyzed for task-evoked activation using an ordinary least squares method of general linear modeling as implemented in the NIRS Brain AnalyzIR Toolbox
Blood Samples Blood samples will be collected from a certified phlebotomist at the Heritage Medical Research Clinic located in the Cal Wenzel Precision Health building at the Foothills Medical Centre Campus Analysis will focus on blood biomarkers of inflammation and CNS injury
Statistical Analysis Outcome parameters within each specific group rTMS sham sex PTSD diagnosis will be analyzed by a one-way repeated measures analysis of variance RM-ANOVA
Mild traumatic injury is considered a risk factor in the development of post-traumatic stress disorder As such post-traumatic stress disorder and mild traumatic brain injury often co-occur and share similar symptoms such as irritability post-traumatic amnesia sleep disturbances concentration difficulties and cognitive processing deficits Several studies have suggested the efficacy and safety of rTMS for the treatment of PTSD however a gap in the literature exists regarding treating comorbid post-traumatic stress disorder and PPCS following mild traumatic brain injury To study potential differences in response to treatment between individuals experiencing PPCS with or without co-morbid post-traumatic stress disorder we intend to measure PTSD symptoms for those with a clinical diagnosis of post-traumatic stress disorder Tracking PTSD symptoms will allow insight into whether the presence of PTSD symptoms affects rTMS treatment outcomes in individuals experiencing PPCS
RESEARCH QUESTIONS AND OBJECTIVES
The overall goal is to study the application of rTMS treatment to the left dorsal lateral prefrontal cortex DLPFC in patients with PPCS to improve overall symptom burden and to explore biomarkers of response specifically functional near infrared spectroscopy fNIRS
Specifically the objectives are
1 Primary Objective to determine changes in brain physiology associated with rTMS treatment as recorded by fNIRS
2 Secondary Objective to determine whether patients with PPCS have significant improvement to a 20-day high frequency rTMS treatment protocol of the left DLPFC compared to patients with PPCS receiving a sham rTMS protocol as measured by the Rivermead post-concussion symptom questionnaire at 1 and 3 months post-treatment
3 Third Objective To determine what exploratory outcomes such as quality of life headaches anxiety depression sleep and somatic symptoms also improve with TMS treatment in individuals suffering with PPCS Quality of life will be measured via the Quality of Life after Brain Injury questionnaire QOLIBRI headache intensity will be measured via the Headache intensity Test - 6 HIT-6 feelings of depression will be measured via the Patient Health Questionnaire -9 PHQ-9 anxiety via the Generalized Anxiety Disorder -7 GAD-7 sleep via the Sleep and Concussion Questionnaire and somatic symptoms which are commonly present in functional neurological disorders via the SOMS-CD and Patient Health Questionnaire-15 PHQ-15 Since Functional Neurological Disorder is often associated with past trauma trauma history will be assessed via the Brief Trauma Questionnaire BTQ and the Life Stress Questionnaire LSQ
4 To determine whether those with PPCS and PTSD respond differently to rTMS and what effect this has on their PTSD symptoms measured via the Clinician-Administered PTSD Scale for DSM-5 CAPS-5 and the Montgomery-Asberg Depression Rating Scale Participants with PTSD will be identified as those with scores higher than 33 in the PCL-5 and a clinical diagnosis of PTSD by a medical professional
5 To examine potential blood biomarkers of post-concussion syndrome and post-traumatic stress disorder
METHODS
This study will be a double-blind sham-controlled concealed allocation randomized clinical trial
Clinical Assessments Demographic information will be collected prior to starting the study including age sex education headache history concussion history past medical history medication use and family medical history Baseline questionnaires will be completed including Headache Impact Test - 6 HIT-6 Rivermead PPCS questionnaire British Columbia post-concussion symptom inventory BC-PSI quality of life after brain injury questionnaire QOLIBRI patient health questionnaire-9 PHQ-9 generalized anxiety disorder scale-7 GADS-7the St Louis University Mental examination Tool SLUMS the screening for somatoform symptoms questionnaire SOMS-CD the post traumatic stress disorder checklist for DSM-5 PCL-5 the Brief Trauma Questionniare BTQ the Life Stress Questionnaire LSQ the Patient Health Questionnaire-15 PHQ-15 and the Sleep and Concussion Questionnaire SCQ Those who are identified as having a PCL-5 score of greater than 33 in addition to a clinical diagnosis of post-traumatic stress disorder will also complete the LEC-5 CAPS-5 MADRS and Columbia Suicide Severity Rating Scale Patients will be reassessed at the completion of their rTMS treatment and at 1 and 3 months post-treatment The questionnaires that will be completed at all follow-up visits include the Rivermead PPCS questionnaire the HIT-6 the BC-PSI the QOLIBRI the PHQ-9 the GAD-7 the PCL-5 the SLUMS the SOMS-CD the PHQ-15 and the Sleep and Concussion Questionnaire For the Sleep and Concussion Questionnaire the initial screening section will not be completed at follow-ups Participants in the PTSD sub-group will also complete the MADRS CAPS-5 and Columbia Suicide Severity Rating Scale at the 1 month and 3-month follow-up visits
TMS Protocol Patients will engage in a four-week treatment protocol 20 treatments This was chosen as it is the midpoint between typical depression and migraine protocol durations A standardized atlas brain with Montreal Neurologic Institute MNI coordinates will be used for navigation The DLPFC will be located through MNI coordinates -50 30 36 The intensity of the rTMS will be 100-120 of resting motor threshold amplitude with a frequency of 10 Hz 10 trains of 60 pulsestrain total of 600 pulses and inter-train interval of 45s In the sham condition a sham coil will be applied to the scalp after the resting motor threshold is determined Patients will be able to hear the sound and feel the vibration of sham coil but will not experience any effective stimulation Previous sham studies have demonstrated efficacy of the blinding method
Imaging Functional near infrared spectroscopy fNIRS measurements will be recorded at baseline immediately following rTMS and at one month and 3-month follow-ups post-rTMS to investigate changes in brain physiology associated with rTMS treatment fNIRS data will be recorded over the frontoparietal cortex at a sampling rate of 391 Hz using the TechEn fNIRS system TechEn Inc Milford MA USA Each recording will consist of a 5 min rest period followed by a finger tapping exercise and a graded working memory task previously described by Hocke et al 2018 The fNIRS data will be processed and analyzed for task-evoked activation using an ordinary least squares method of general linear modeling as implemented in the NIRS Brain AnalyzIR Toolbox
Blood Samples Blood samples will be collected from a certified phlebotomist at the Heritage Medical Research Clinic located in the Cal Wenzel Precision Health building at the Foothills Medical Centre Campus Analysis will focus on blood biomarkers of inflammation and CNS injury
Statistical Analysis Outcome parameters within each specific group rTMS sham sex PTSD diagnosis will be analyzed by a one-way repeated measures analysis of variance RM-ANOVA
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None