Phase II Clinical Trial of Transcranial Direct Current Stimulation in the Treatment of Primary Progressive Aphasia
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 180
- 试验地点
- 6
- 主要终点
- Immediate Change in Phonemic Accuracy
研究概览
简要总结
While many have strongly suggested that transcranial direct current stimulation (tDCS) may represent a beneficial intervention for patients with primary progressive aphasia (PPA), this promising technology has not yet been applied widely in clinical settings. This treatment gap is underscored by the absence of any neurally-focused standard-of-care treatments to mitigate the devastating impact of aphasia on patients' family, work, and social lives. Given that tDCS is inexpensive, easy to use (it is potentially amenable to home use by patients and caregivers), minimally invasive, and safe there is great promise to advance this intervention toward clinical use. The principal reason that tDCS has not found wide clinical application yet is that its efficacy has not been tested in large, multi-center, clinical trials. In this study, scientists in the three sites that have conducted tDCS clinical trials in North America-Johns Hopkins University and the University of Pennsylvania in the US, and the University of Toronto in Canada, will collaborate to conduct a multi-site, Phase II clinical trial of tDCS a population in dire need of better treatments.
详细描述
Aim 1: To determine whether tDCS over the left perisylvian language areas paired with naming treatment will improve oral and written naming outcomes in two variants of PPA (nfvPPA and lvPPA).
The investigators will use a double-blind, sham-controlled, within-subject, cross-over design. Participants will receive Naming and Spelling (NASP) treatment + tDCS condition or NASP treatment + sham condition, in Period 1 or 2, randomized for the Period 1 stimulation condition. Each treatment period will last 3 weeks, with 5 language therapy sessions/week, for 15 sessions in total, and a 3-month (stimulation-free) wash-out time between the two periods of stimulation to evaluate clinically meaningful effects.
Language therapy (NASP treatment) will be delivered by a speech-language pathologist or a trained research associate. The participant will be shown a picture on the screen, asked to orally name it, and subsequently write the name. If the participant cannot, the participant will be asked to provide 3 semantic attributes to reinforce semantic representations, as in Semantic Feature Analysis treatment (Boyle, 2010). If the word still cannot be named or written, the clinician will provide the correct name and spelling and the participant will be asked to repeat or copy it 3 times, in a spell-study-spell procedure (Rapp & Glucroft, 2009). There will be two word-sets: trained (targeted during therapy) and untrained (not targeted during therapy), both individually tailored to the participant based on severity of spelling deficit. Treatment stimuli will consist of 10-30 words depending on individual severity. General procedures and the outcome measure (letter accuracy) will be maintained across all participants. Consistent with the investigators previous work, the NASP treatment will be conducted in English, which, for most participants, will be the participant's first language.
To deliver tDCS, the investigators will use the Soterix 1x1 platform. The anode will be placed over the left frontal lobe, centered on F7 in the 10-20 electrode placement system (Homan, 1988), and cathode will be placed over the right cheek. Non-metallic, conductive rubber electrodes (5 cm x 5 cm), fitted with saline-soaked sponges to limit skin-electrode reactions will be used so the full left inferior frontal gyrus (IFG) will be covered. Current will be delivered with an intensity of 2 mA (estimated current density 0.08 milliamps (mA)/cm2) for a total of 20 minutes each tDCS session. Delivery of tDCS will be simultaneous with the start of language therapy, which will continue for an additional 25 minutes beyond the cessation of tDCS in each session. In contrast to actual tDCS, sham stimulation involves the delivery of 30 seconds of current ramping up to 2 mA and back down to 0 mA simultaneous with the start of language therapy.
Behavioral/language assessments will involve: oral and written naming, spelling, connected speech/discourse, sentence comprehension and production, verbal fluency, short-term/working memory tasks, etc. Other global cognitive assessments will be conducted, as well as quality of life assessments. Bilingual assessments will be conducted for those who bilingual or multilingual.
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, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Presence of aphasia attributable to non-fluent PPA or logopenic PPA
- •High school education (or more)
- •Between the ages of 50 and 80
- •Must be able to understand the nature of the study and give informed consent
排除标准
- •Cognitive impairment of sufficient severity to preclude giving informed consent (Mini Mental State Examination [MMSE] less than 15)
- •Any unrelated neurologic or physical condition that impairs communication ability
- •History of unrelated neurological conditions, including but not limited to traumatic brain injury (TBI), stroke, or small vessel disease, that has resulted in a neurologic deficit
- •Any additional neurological condition that would likely reduce the safety of study participation, including central nervous system (CNS) vasculitis, intracranial tumor, intracranial aneurysm, multiple sclerosis, or arteriovenous malformations
- •A medically unstable cardiopulmonary or metabolic disorder
- •Individuals with pacemakers or implantable cardiac defibrillators
- •Terminal illness associated with survival of less than 12 months
- •Major active psychiatric illness that may interfere with required study procedures or treatments, as determined by the enrolling physician
- •Current abuse of alcohol or drugs, prescription or otherwise
- •Participant in another drug, device, or biologics trial within 30 days prior to enrollment
- •Nursing a child, pregnant, or intending to become pregnant during the study
- •Left-handedness
- •Exclusion for tDCS, specifically:
- •History of spontaneous or partial complex seizures or unexplained loss of consciousness within 6 months of enrollment
- •Subjects with metallic objects in the face or head other than dental apparatus, such as braces, fillings, or implants
- •Subjects with previous craniotomy or any breach in the skull
- •Exclusion for MRI, specifically:
- •Presence of any of the following devices: cardiac pacemaker, other pacemakers (for carotid sinus, insulin pumps, nerve stimulators, lead wires or similar wires), optic implant, implanted cardiac defibrillator, aneurysm clip, any electronically/magnetically/mechanically activated implant, ferromagnetic implants (coils, filters, stents; metal sutures or staples)
- •Presence of any of the following: pregnancy, claustrophobia, metal in eye or orbit, tattooed eyeliner
结局指标
主要结局
Immediate Change in Phonemic Accuracy
时间窗: Baseline and Immediate follow-up of 3-week intervention period
The primary outcome measure will be tDCS-induced change in performance on phonemic accuracy of trained items. Phonemic accuracy will be calculated on a scale of 0-100% with a higher number reflecting higher accuracy. The change in performance from baseline will be compared between the tDCS condition and the sham condition.
Immediate Change in Letter Accuracy
时间窗: Baseline and Immediate follow-up of 3-week intervention period
The primary outcome measure will be tDCS-induced change in performance on letter accuracy of trained items. Letter accuracy will be calculated on a scale of 0-100% with a higher number reflecting higher accuracy. The change in performance from baseline will be compared between the tDCS condition and the sham condition.
Change in Phonemic Accuracy at 3-month follow-up visit
时间窗: Baseline and 3 months post intervention
The primary outcome measure will be tDCS-induced change in performance on phonemic accuracy of trained items, 3 months following the discontinuation of intervention. Phonemic accuracy will be calculated on a scale of 0-100% with a higher number reflecting higher accuracy. The change in performance from baseline will be compared between the tDCS condition and the sham condition.
Change in Letter Accuracy at 3-month follow-up visit
时间窗: Baseline and 3 months post intervention
The primary outcome measure will be tDCS-induced change in performance on letter accuracy of trained items, 3 months following the discontinuation of intervention. Letter accuracy will be calculated on a scale of 0-100% with a higher number reflecting higher accuracy. The change in performance from baseline will be compared between the tDCS condition and the sham condition.
次要结局
- Change in Untrained Naming Items (letter accuracy)(Baseline and 3 months post intervention)
- Change in Untrained Naming Items (phonemic accuracy)(Baseline and 3 months post intervention)
- Change in functional connectivity of select brain regions (z-correlations)(Immediate follow-up of 3-week intervention period and 3-month follow-up)