Accelerated rTMS for Post-Stroke Apathy: Targeting Amotivation Toward Improving Whole Health and Rehabilitation Engagement
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 2
- 主要终点
- Change From Baseline Cognition, as Measured by the Fluid Cognition Composite Score From the NIH Toolbox Cognition Battery compared to baseline
研究概览
简要总结
This pilot study will investigate the safety, feasibility, tolerability, and preliminary efficacy of accelerated high-dose repetitive transcranial magnetic stimulation (rTMS) targeting the medial prefrontal cortex (mPFC) to address apathy symptoms in individuals with chronic stroke.
详细描述
Repetitive transcranial magnetic stimulation (rTMS) is a well-established FDA-approved treatment for several psychiatric indications including treatment-resistant depression, obsessive-compulsive disorder, and smoking cessation. Traditional rTMS targets the dorsolateral prefrontal cortex (dlPFC) with repetitive treatments delivered for six weeks. Recent innovations have led to the development of accelerated, high-dose rTMS protocols, with recent FDA-approval, that are capable of delivering a full treatment course within a single week.
Accumulating evidence suggests that similar neuromodulation protocols may be helpful in targeting neuropsychiatric symptoms across a range of neurologic and neurodegenerative conditions including dementia, movement disorders, and stroke. Apathy is a distinct neuropsychiatric symptom characterized by loss of motivation, withdrawal, and decreased goal-directed activity seen across a wide range of neuropsychiatric conditions. Apathy contributes significantly to lower quality of life, caregiver burnout, and poorer rehabilitation outcomes. Meanwhile, there are currently no FDA-approved treatments targeting apathy specifically. The mPFC has been well-established as a safe and feasible target for traditional rTMS, and may be a desirable stimulation site in targeting apathy due to its superficial location and integral association with other brain structures implicated in apathy pathophysiology such as the anterior cingulate cortex (ACC) and ventral striatum (VL).
This phase I open-label pilot study will investigate high-dose, accelerated rTMS at the medial prefrontal cortex (mPFC) to target apathy in individuals with chronic stroke. The primary aims of the study will be to: (1) establish the safety, feasibility, tolerability, and acceptability of an accelerated repetitive transcranial magnetic stimulation (rTMS) protocol for apathy in chronic stroke; (2) establish the feasibility of individualized resting-state functional magnetic resonance imaging (fMRI) connectivity for targeting rTMS in post-stroke apathy; (3) establish preliminary efficacy of an accelerated rTMS protocol for post-stroke apathy. Given the limited power of this small pilot study, this aim will be considered exploratory with the intention to guide future research.
Sixteen chronic stroke patients with symptomatic apathy will complete (1) structural as well as resting state functional MRI at baseline for targeting parcellations. (2) A battery of validated clinical assessments of apathy-related symptoms (3) a battery of neuropsychological, cognitive, and symptom measures to assess safety, tolerability, and feasibility. Treatment will consist of open-label, high-dose rTMS to left mPFC delivered following a standard protocol consisting of 600 pulses, twelve times per day, for three treatment days (contiguous or non-contiguous) within a seven-day period. Safety assessments will be monitored throughout treatment. A battery of clinical assessments will be repeated at the end of treatment and weekly for one month post-treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Device Feasibility
- 盲法
- None
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •40 years old or greater
- •Right- or left-hemisphere ischemic or hemorrhagic stroke with at least 6 months chronicity
- •Symptomatic apathy as confirmed by (A) total score on the Apathy Evaluation Scale (AES) of ≥39 as rated by the participant or caregiver informant
- •Intact cortex under the coil at the stimulation target site confirmed by neuroimaging
- •Ability to participate in psychometric testing and cognitive tasks
排除标准
- •Primary extra-axial hemorrhage (subdural or subarachnoid) without ischemic stroke or intraparenchymal hemorrhage
- •Concomitant neurological disorders affecting motor or cognitive function (e.g. dementia)
- •Moderate or severe global aphasia
- •Visual impairment precluding completion of cognitive tasks
- •Presence of contraindications to MRI or TMS including electrically, magnetically or mechanically activated metal or nonmetal implants such as cardiac pacemakers, intracerebral vascular clips, or any other electrically sensitive support system;
- •Pregnancy (to be later confirmed by UPT in any premenopausal female participants)
- •History of a seizure disorder
- •Preexisting scalp lesion, wound, bone defect, or hemicraniectomy
- •Claustrophobia precluding the ability to undergo an MRI
- •Active substance use disorder
- •Psychotic disorders
- •Bipolar 1 Disorder
- •Acute suicidality as assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) or suicide attempt in the previous year
研究组 & 干预措施
Repetitive transcranial magnetic stimulation
All participants will receive accelerated, high-dose repetitive transcranial magnetic stimulation (rTMS) at the medial prefrontal cortex (mPFC) delivered in runs of 600 pulses, twelve times per day, for three treatment days (contiguous or non-contiguous) within a seven-day period.
干预措施: MagVenture MagPro Transcranial Magnetic Stimulation (TMS) System (Device)
结局指标
主要结局
Change From Baseline Cognition, as Measured by the Fluid Cognition Composite Score From the NIH Toolbox Cognition Battery compared to baseline
时间窗: Pre-treatment, immediately post-treatment
Fluid cognition was measured using the iPad-administered NIH Toolbox Cognition Battery (NIHTB-CB). Fluid Cognition Composite scores were calculated by averaging the demographically adjusted (age, education, sex, race/ethnicity; Casaletto et al., 2015) T-scores for 4 NIHTB-CB tests: the flanker inhibitory control, list sorting working memory, pattern comparison processing speed, and dimensional change card sort tests. T-Scores have a mean of 50 and a standard deviation of 10. Lower scores indicate worse performance.
Patient perception of treatment acceptability as assessed by study-specific questionnaire
时间窗: After each session of rTMS during each of three treatment days within one week, and at one month post-treatment follow-up
A 15-item study-specific questionnaire of rTMS treatment acceptability, with each item rated on a scale from 1 to 5 (1 = not at all, 3 = somewhat, 5 = very much so). Higher scores indicate better acceptability for the first 10 items, lower scores indicate better acceptability for the last 5 items.
Incidence of Treatment-Emergent Adverse Events and Side Effects as assessed by change in the Review of Systems Criteria compared to baseline
时间窗: After each session of rTMS during each of three treatment days within one week
A review of systems questionnaire will be administered to rate the subjective symptom (headache, scalp pain, arm/hand pain, other pain(s), numbness/tingling, other sensation(s), weakness, loss of dexterity, vision/hearing change(s), ear ringing, nausea/vomiting, appetite loss, rash, skin change(s) or any other symptom(s)) on a scale of 0 to 5 (none, minimal, mild, moderate, marked, severe).
Change in global cognition, as measured by the Montreal Cognitive Assessment (MoCA) compared to baseline
时间窗: Pre-treatment, immediately post-treatment, and at one month post-treatment follow-up
The Montreal Cognitive Assessment (MoCA) is a clinical assessment of cognitive function. The MoCA assesses multiple cognitive domains including memory, visuospatial skills, executive function, attention, concentration, calculation, language, abstraction, and orientation. The MoCA can be administered in approximately 10 minutes and total scores range from 0 to 30 with lower scores correlating with greater degree of cognitive impairment.
Participant retention rate
时间窗: calculated at the end of the study follow-up assessment period (one month post-treatment)
Percentage of participants who completed the study relative to all participants who initiated treatment (target n=16). Percentage of participants who completed the study relative to all participants who initiated treatment (target n=16). Percentage of participants who completed the study relative to all participants who initiated treatment (target n=16).
Change in apathy symptoms, as measured by the Lille Apathy Rating Scale (LARS) compared to baseline
时间窗: Pre-treatment, immediately post-treatment, and weekly for four weeks post-treatment
The Lille Apathy Rating Scale (LARS) is a clinically validated 33-item structured interview assessing clinical symptoms of apathy. The structured interview is broken into 9 sub-scales including everyday productivity, interests, taking the initiative, novelty seeking, motivation, emotional responsiveness, concern, and social life. Total scores can range from -36 to +36 and are further stratified by factorial sub-scores including intellectual curiosity, emotion, action initiation, and self-awareness.
Change in Apathy Symptoms, as Measured by the Lille Apathy Rating Scale (LARS) Compared to Baseline
时间窗: Pre-treatment, immediately post-treatment, and at one-month follow-up
The Lille Apathy Rating Scale (LARS) is a validated 33-item structured interview assessing apathy across 9 domains, including intellectual curiosity, emotion, action initiation, self-awareness, productivity, interests, novelty seeking, motivation, and social engagement. Total scores range from -36 to +36, with higher scores indicating greater severity of apathy (worse outcome) and lower (more negative) scores indicating less apathy (better outcome). The total score is calculated by summing responses across all items and domains to generate a composite score.
Treatment-Emergent Adverse Events and Side Effects as Assessed by Intermittent Theta Burst Stimulation Review of Systems (iTBS ROS)
时间窗: Across the 3 rTMS treatment days
A review of systems questionnaire (Intermittent Theta Burst Stimulation Review of Systems; iTBS ROS) was administered repeatedly during each treatment day to assess treatment-emergent symptoms. Symptoms were rated on a scale from 0 to 5 (0 = none, 1 = minimal, 2 = mild, 3 = moderate, 4 = marked, 5 = severe), with higher scores indicating greater symptom severity (worse outcome). Values reported represent the average symptom severity across all assessments collected during the 3 treatment days for each participant, and then averaged across participants.
Change in Global Cognition, as Measured by the Montreal Cognitive Assessment (MoCA) Compared to Baseline
时间窗: Pre-treatment, immediately post-treatment, and at one-month follow-up
The Montreal Cognitive Assessment (MoCA) is a clinical assessment of cognitive function. The MoCA assesses multiple cognitive domains including memory, visuospatial skills, executive function, attention, concentration, calculation, language, abstraction, and orientation. The MoCA can be administered in approximately 10 minutes and total scores range from 0 to 30 with lower scores correlating with greater degree of cognitive impairment.
Change From Baseline Cognition, as Measured by the Fluid Cognition Composite Score From the NIH Toolbox Cognition Battery Compared to Baseline
时间窗: Pre-treatment, immediately post-treatment
Fluid cognition was measured using the iPad-administered NIH Toolbox Cognition Battery (NIHTB-CB). Fluid Cognition Composite scores were calculated by averaging the demographically adjusted (age, education, sex, race/ethnicity; Casaletto et al., 2015) T-scores for 5 NIHTB-CB tests: the flanker inhibitory control, list sorting working memory, pattern comparison processing speed, dimensional change card sort tests, and picture sequence memory. T-Scores have a mean of 50 and a standard deviation of 10. Lower scores indicate worse performance. There are no established thresholds or cutoffs for clinically distinct or diagnostic categories.
Participant Retention Rate
时间窗: calculated at the end of the study follow-up assessment period (one month post-treatment)
Percentage of participants who completed the study relative to all participants who initiated treatment
次要结局
- Change in apathy symptoms, as measured by the Apathy Evaluation Scale (AES) compared to baseline(Pre-treatment, immediately post-treatment, and at one month post-treatment follow-up)
- Patient-Reported Outcomes Measurement Information System (PROMIS) Depression Short Form(Pre-treatment, immediately post-treatment, and weekly for four weeks post-treatment)
- Change in Apathy Symptoms, as Measured by the Apathy Evaluation Scale (AES) Compared to Baseline(Pre-treatment, immediately post-treatment, and at one-month follow-up)
- Patient-Reported Outcomes Measurement Information System (PROMIS) Depression Short Form(Pre-treatment, immediately post-treatment, and at one-month follow-up)
研究者
Parneet Grewal
Assistant Professor-Faculty
Medical University of South Carolina