A Randomized, Double-blinded, Sham-controlled Cross-over Study of Theta-burst Transcranial Magnetic Stimulation in Nonfluent/Agrammatic Variant Primary Progressive Aphasia
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 2
- 主要终点
- Tolerability levels according to the daily Comfort Rating Questionnaire (CRQ)
研究概览
简要总结
Nonfluent/agrammatic variant primary progressive aphasia (nf/avPPA) is a fatal neurodegenerative disease that begins with isolated language deficits. There is currently no cure or treatment for this disease. Repetitive Transcranial Magnetic Stimulation (rTMS), a noninvasive neuromodulatory technique, is effective in major depression, and studied in many other conditions including nf/avPPA. Here the investigators propose to study the feasibility and change in language and brain function of a newer rTMS protocol (intermittent theta-burst stimulation, iTBS) using a randomized, blinded crossover design: participants will receive active or sham iTBS for two weeks and then switch groups without them or clinicians knowing their group. The investigators hypothesize that brain function and performance with language tasks will change after active iTBS.
详细描述
This study is a randomized controlled blinded cross-over treatment trial that involves 20 iTBS treatment sessions (10 active treatment sessions; 10 sham treatment sessions) and the study will last between 6 weeks. There will be 20 treatment visits (Monday-Friday) each lasting 10-40 minutes. Whether the participant is randomly assigned to active or sham treatment, the participant will receive daily 10 minute session of iTBS treatment. Some sessions will include behavioral and neurophysiological measures.
In addition, participants will complete cognitive testing, and neuro-imaging, including functional magnetic resonance (fMRI), functional near infrared spectroscopy (fNIRS) and electroencephalography (EEG) prior to the commencement of iTBS/sham treatment and at post-treatment. Safety and tolerability will be evaluated during daily iTBS treatments.
After 10 iTBS treatment visits over 2 weeks, a clinical assessment will be done to see if the participants are responding to the iTBS treatment with a targeted language assessment and neuro-imaging as described above. After 2 weeks of "wash-out", where the subjects do not receive any treatments, the participants will undergo another 2 weeks of iTBS treatment. On the first iTBS session after the 2-week washout period, participants will undergo a targeted language assessment and EEG/fNIRS. At the final iTBS session at 6 weeks, subjects will again undergo a targeted language assessment, EEG/fNIRS, and fMRI. At that point, after 6 weeks, the cross-over study is finished.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinically diagnosed with nonfluent-agrammatic variant primary progressive aphasia (nfvPPA), by 2011 Gorno-Tempini diagnostic criteria.
- •Frontotemporal lobar degeneration modified clinical dementia rating scale (FTLD-CDR) score ≤4 (mild).
- •Is voluntary and competent to consent to treatment, or if demented, to assent and co-consent can be obtained by their legal next-of-kin, legal guardian, or substitute decision maker.
- •Speaks English enough to be able to complete neuropsychological testing.
- •Able to adhere to the treatment schedule.
- •Has a study partner available to answer the Progressive Aphasia Severity Scale (PASS) questionnaire.
排除标准
- •Uncorrected visual or hearing impairment by self report.
- •History of substance dependence or abuse within the last 3 months.
- •Has active suicidal intent.
- •Has a lifetime Mini-International Neuropsychiatric Interview (MINI) diagnosis of major depressive disorder, bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms.
- •Concomitant major unstable medical illness, cardiac pacemaker or implanted medication pump.
- •Any significant neurological disorder other than nfvPPA including, but not limited to: any condition likely to be associated with increased intracranial pressure, space occupying brain lesion, history of epilepsy, known cerebral aneurysm, Parkinson's disease, Huntington's chorea, multiple sclerosis, significant head trauma with loss of consciousness for greater than or equal to 5 minutes in the previous 6 months.
- •Is currently (or in the last 4 weeks) taking lorazepam greater than 2 mg daily (or equivalent) or any dose of an anticonvulsant, due to the potential to limit rTMS efficacy.
- •Exclusion Criteria for TMS Participation:
- •Does not pass the TMS adult safety screening (TASS) questionnaire (e.g. has an intracranial implant)
- •Exclusion Criteria for MRI Participation:
- •Severe claustrophobia.
- •Cardiac pacemakers or ferromagnetic implants.
- •Pregnant women.
结局指标
主要结局
Tolerability levels according to the daily Comfort Rating Questionnaire (CRQ)
时间窗: 6 weeks
Tolerability will be measured by daily Comfort Rating Questionnaire (CRQ) between sham and active interventions and compared using Chi-square. A mean score across all treatment sessions above 6 on more than 2 items on the CRQ will be considered as severe. A mean score across all treatment sessions between 4 and 6 on more than 2 items on the CRQ will be considered as moderate tolerability. A mean score across all treatment sessions below 4 on the majority of items will be considered as mild tolerability.
Drop out rate
时间窗: 6 weeks
Feasibility will be measured by drop out rate. A drop out rate \>50% will be considered as an indication of non-feasibility of current protocol.
Incidence of treatment-emergent adverse events
时间窗: 6 weeks
Safety will be measured by incidence of treatment-emergent adverse events
次要结局
- Changes in the Verb and Object Naming Test score(6 weeks)
- Changes in the Sentence Comprehension Test score(6 weeks)
- Changes in the Montreal Cognitive Assessment Battery score(6 weeks)
- Changes in the Clinical Global Impression of Change score(6 weeks)
- Changes in the Western Aphasia Battery rating(6 weeks)
- Changes in the Make a Sentence Test score(6 weeks)
- Changes in the Apraxia of Speech Rating Scale score(6 weeks)
- Changes in the Progressive Aphasia Severity Scale rating(6 weeks)
- Changes in the whole-brain functional connectivity measured using functional Magnetic Resonance Imaging (MRI)(6 weeks)
- Changes in the Frontal Assessment Battery score(6 weeks)
- Changes in the brain cortical blood oxygenation measured using functional Near Infrared Spectroscopy (fNIRS)(6 weeks)
- Changes in the brain cortical electrical activity measured using quantitative electroencephalography (EEG)(6 weeks)
研究者
Fidel Vila-Rodriguez
Assistant Professor
University of British Columbia