Clinical Trial: Transcranial Magnetic Stimulation in Nonfluent/Agrammatic Variant Primary Progressive Aphasia

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: A Randomized, Double-blinded, Sham-controlled Cross-over Study of Theta-burst Transcranial Magnetic Stimulation in Nonfluent/Agrammatic Variant Primary Progressive Aphasia

Brief Summary: 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.

Detailed Summary:

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.

Current Primary Outcome:

• Incidence of treatment-emergent adverse events [ Time Frame: 6 weeks ]
  Safety will be measured by incidence of treatment-emergent adverse events
• Tolerability levels according to the daily Comfort Rating Questionnaire (CRQ) [ Time Frame: 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 [ Time Frame: 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.

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Changes in the Verb and Object Naming Test score [ Time Frame: 6 weeks ]
  Verb and Object Naming Test score at baseline and at 2, 4, and 6 weeks
• Changes in the Make a Sentence Test score [ Time Frame: 6 weeks ]
  Make a Sentence Test score at baseline and at 2, 4, and 6 weeks
• Changes in the Sentence Comprehension Test score [ Time Frame: 6 weeks ]
  Sentence Comprehension Test score at baseline and at 2, 4, and 6 weeks
• Changes in the Apraxia of Speech Rating Scale score [ Time Frame: 6 weeks ]
  Apraxia of Speech Rating Scale score at baseline and at 6 weeks
• Changes in the Clinical Global Impression of Change score [ Time Frame: 6 weeks ]
  Clinical Global Impression of Change score at baseline and at 2, 4, and 6 weeks
• Changes in the Progressive Aphasia Severity Scale rating [ Time Frame: 6 weeks ]
  Progressive Aphasia Severity Scale rating at baseline and at 6 weeks
• Changes in the Western Aphasia Battery rating [ Time Frame: 6 weeks ]
  Western Aphasia Battery rating at baseline and at 6 weeks
• Changes in the Montreal Cognitive Assessment Battery score [ Time Frame: 6 weeks ]
  Montreal Cognitive Assessment Battery score at baseline and at 6 weeks
• Changes in the Frontal Assessment Battery score [ Time Frame: 6 weeks ]
  Frontal Assessment Battery score at baseline and at 6 weeks
• Changes in the whole-brain functional connectivity measured using functional Magnetic Resonance Imaging (MRI) [ Time Frame: 6 weeks ]
  fMRI at baseline and at 2 and 6 weeks
• Changes in the brain cortical blood oxygenation measured using functional Near Infrared Spectroscopy (fNIRS) [ Time Frame: 6 weeks ]
  fNIRS at baseline and at 2, 4, and 6 weeks
• Changes in the brain cortical electrical activity measured using quantitative electroencephalography (EEG) [ Time Frame: 6 weeks ]
  EEG at baseline and at 2, 4, and 6 weeks

Original Secondary Outcome: Same as current

Information By: University of British Columbia

Dates:
Date Received: March 1, 2017
Date Started: June 1, 2017
Date Completion: March 1, 2018
Last Updated: May 12, 2017
Last Verified: May 2017