Functional Near Infrared Spectroscopy as a Biomarker of Response in Patients With Post-concussion Syndrome Treated With Transcranial Magnetic Stimulation
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 91
- 试验地点
- 2
- 主要终点
- Rivermead Post-Concussion Symptom Questionnaire (RPQ)
研究概览
简要总结
Every year, approximately 2 million people in the United States and 280,000 in Canada experience a mild traumatic brain injury/concussion. 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.
详细描述
Annually, up to 280,000 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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Patients will be randomized with a random number generator to receive either sham or rTMS. The research assistant administering the fNIRS and PTSD assessments, will be blinded to the treatment allocations. Once the study is completed, patients and all study personnel will be unblinded. Subjects in the sham group will be given the opportunity to cross over to the treatment group.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of persistent post-concussion syndrome based on the ICD-10 criteria. This diagnosis should be given to the patient from a clinical practitioner.
- •Concussion in the past 5 years attributed to current symptoms.
- •Age 18-75 yrs.
- •Current pharmacologic management can remain stable throughout the protocol such as use of abortive headache medications (i.e. triptans, opioids, tricyclic antidepressants, anti-seizure medications).
排除标准
- •Prior history of TMS therapy
- •TMS-related contraindications (pacemaker, metallic implant)
- •Other medical conditions such as structural brain disease, previous seizures, psychiatric disorders excluding depression, PTSD and anxiety (schizophrenia, bipolar disorder), liver or kidney disease, malignancy, uncontrolled hypertension or diabetes, and pregnancy.
结局指标
主要结局
Rivermead Post-Concussion Symptom Questionnaire (RPQ)
时间窗: 3-months post-intervention
Assesses the severity of 16 commonly experienced PCS symptoms. Participants are instructed to rate the extent to which they have suffered from each of the listed symptoms in the past 24 hours, as compared to pre-injury levels, using a scale of 0 ("not experienced at all") to 4 ("a severe problem"). The RPQ has been demonstrated as a valid measure of PPCS with a minimal clinically important difference (MCID) of 4.5 points. It is advised to analyze this assessment as two separate scales (RPQ-13 and RRQ-3). The RPQ-3 has a total possible score of 0-12, with higher scores indicative of worse outcomes. The RPQ-13 has a total possible score of 0-52, with higher scores indicative of worse outcomes. Using these sub-scales, the instrument has good test-retest reliability and external construct validity. This questionnaire probes the separate cognitive, emotional and somatic components of PPCS.
次要结局
- Saint Louis University Mental Status Examination (SLUMS)(3-months post-intervention)
- Brief Trauma Questionnaire(3-months post-intervention)
- Patient Health Questionnaire (PHQ-9)(3-months post-intervention)
- Quality of Life After Brain Injury (QOLIBRI)(3-months post-intervention)
- Headache Impact Test (HIT-6)(3-months post-intervention)
- Post-traumatic Stress Disorder Checklist for DSM-5 (PCL-5)(3-months post-intervention)
- Sleep and Concussion Questionnaire(3-months post-intervention)
- Generalized Anxiety Disorder-7 (GAD-7)(3-months post-intervention)
- Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)(3-months post-intervention)
- British Columbia Post-concussion Symptom Inventory(3-months post-intervention)
- Patient Health Questionnaire-15 (PHQ-15)(3-months post-intervention)
- Montgomery-Asberg Depression Rating Scale(3-months post-intervention)
- Screening for Somatoform Symptoms-7 (SOMS-7 CD Sub-scale)(3-months post-intervention)
- Life Stress Questionnaire(3-months post-intervention)
- Columbia Suicide Severity Rating Scale(3-months post-intervention)