- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03153540
Transcranial Magnetic Stimulation in Nonfluent/Agrammatic Variant Primary Progressive Aphasia
A Randomized, Double-blinded, Sham-controlled Cross-over Study of Theta-burst Transcranial Magnetic Stimulation in Nonfluent/Agrammatic Variant Primary Progressive Aphasia
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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British Columbia
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Vancouver, British Columbia, Canada, V6T2A1
- Non-Invasive Neurostimulation Therapies lab, University of British Columbia
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Active iTBS
Device: MagPro X100 stimulator equipped with the B65 fluid-cooled coil for dominant Inferior Frontal Gyrus (IFG) stimulation (MagPro, Medtronic). Intervention: 10 sessions daily of iTBS over 2 weeks. Active-iTBS consists of intermittent Theta Burst Stimulation to the dominant IFG (120% of resting motor threshold, bursts of 3 pulses at 50 Hz, bursts repeated at 5 Hz for 600 pulses total over 3 min). |
Intermittent theta burst transcranial magnetic stimulation
|
Sham Comparator: Sham iTBS
Device: MagPro X100 stimulator applied to dominant inferior frontal lobe. Intervention: 10 sessions daily of sham iTBS over 2 weeks. Sham sessions involve a click replicating the sound of the magnetic discharge, without any magnetic pulse being delivered. |
Sham intervention
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of treatment-emergent adverse events
Time Frame: 6 weeks
|
Safety will be measured by incidence of treatment-emergent adverse events
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6 weeks
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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.
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6 weeks
|
Drop out rate
Time Frame: 6 weeks
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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.
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6 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in the Verb and Object Naming Test score
Time Frame: 6 weeks
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Verb and Object Naming Test score at baseline and at 2, 4, and 6 weeks
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6 weeks
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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
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6 weeks
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Changes in the Sentence Comprehension Test score
Time Frame: 6 weeks
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Sentence Comprehension Test score at baseline and at 2, 4, and 6 weeks
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6 weeks
|
Changes in the Apraxia of Speech Rating Scale score
Time Frame: 6 weeks
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Apraxia of Speech Rating Scale score at baseline and at 6 weeks
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6 weeks
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Changes in the Clinical Global Impression of Change score
Time Frame: 6 weeks
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Clinical Global Impression of Change score at baseline and at 2, 4, and 6 weeks
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6 weeks
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Changes in the Progressive Aphasia Severity Scale rating
Time Frame: 6 weeks
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Progressive Aphasia Severity Scale rating at baseline and at 6 weeks
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6 weeks
|
Changes in the Western Aphasia Battery rating
Time Frame: 6 weeks
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Western Aphasia Battery rating at baseline and at 6 weeks
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6 weeks
|
Changes in the Montreal Cognitive Assessment Battery score
Time Frame: 6 weeks
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Montreal Cognitive Assessment Battery score at baseline and at 6 weeks
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6 weeks
|
Changes in the Frontal Assessment Battery score
Time Frame: 6 weeks
|
Frontal Assessment Battery score at baseline and at 6 weeks
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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
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6 weeks
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Changes in the brain cortical blood oxygenation measured using functional Near Infrared Spectroscopy (fNIRS)
Time Frame: 6 weeks
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fNIRS at baseline and at 2, 4, and 6 weeks
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6 weeks
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Changes in the brain cortical electrical activity measured using quantitative electroencephalography (EEG)
Time Frame: 6 weeks
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EEG at baseline and at 2, 4, and 6 weeks
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6 weeks
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Fidel Vila-Rodriguez, MD, University of British Columbia
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Metabolic Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neurologic Manifestations
- Neurobehavioral Manifestations
- Neurocognitive Disorders
- Neurodegenerative Diseases
- TDP-43 Proteinopathies
- Proteostasis Deficiencies
- Dementia
- Language Disorders
- Communication Disorders
- Speech Disorders
- Frontotemporal Lobar Degeneration
- Aphasia
- Frontotemporal Dementia
- Aphasia, Primary Progressive
- Pick Disease of the Brain
- Aphasia, Broca
- Primary Progressive Nonfluent Aphasia
Other Study ID Numbers
- H16-01327
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Primary Progressive Nonfluent Aphasia
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