Back to resultsTranscranial Magnetic Stimulation in Nonfluent/Agrammatic Variant Primary Progressive Aphasia
Primary Purpose
Primary Progressive Nonfluent Aphasia
Status
Terminated
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Active iTBS
Sham iTBS
Sponsored by
About this trial
This is an interventional treatment trial for Primary Progressive Nonfluent Aphasia focused on measuring Aphasia, Agrammatism, Frontotemporal Dementia, Tauopathies, Neurodegenerative Diseases, Language Disorders, Frontotemporal Lobar Degeneration
Eligibility Criteria
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.
Sites / Locations
- Non-Invasive Neurostimulation Therapies lab, University of British Columbia
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Sham Comparator
Arm Label
Active iTBS
Sham iTBS
Arm Description
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).
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.
Outcomes
Primary Outcome Measures
Incidence of treatment-emergent adverse events
Safety will be measured by incidence of treatment-emergent adverse events
Tolerability levels according to the daily Comfort Rating Questionnaire (CRQ)
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
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.
Secondary Outcome Measures
Changes in the Verb and Object Naming Test score
Verb and Object Naming Test score at baseline and at 2, 4, and 6 weeks
Changes in the Make a Sentence Test score
Make a Sentence Test score at baseline and at 2, 4, and 6 weeks
Changes in the Sentence Comprehension Test score
Sentence Comprehension Test score at baseline and at 2, 4, and 6 weeks
Changes in the Apraxia of Speech Rating Scale score
Apraxia of Speech Rating Scale score at baseline and at 6 weeks
Changes in the Clinical Global Impression of Change score
Clinical Global Impression of Change score at baseline and at 2, 4, and 6 weeks
Changes in the Progressive Aphasia Severity Scale rating
Progressive Aphasia Severity Scale rating at baseline and at 6 weeks
Changes in the Western Aphasia Battery rating
Western Aphasia Battery rating at baseline and at 6 weeks
Changes in the Montreal Cognitive Assessment Battery score
Montreal Cognitive Assessment Battery score at baseline and at 6 weeks
Changes in the Frontal Assessment Battery score
Frontal Assessment Battery score at baseline and at 6 weeks
Changes in the whole-brain functional connectivity measured using functional Magnetic Resonance Imaging (MRI)
fMRI at baseline and at 2 and 6 weeks
Changes in the brain cortical blood oxygenation measured using functional Near Infrared Spectroscopy (fNIRS)
fNIRS at baseline and at 2, 4, and 6 weeks
Changes in the brain cortical electrical activity measured using quantitative electroencephalography (EEG)
EEG at baseline and at 2, 4, and 6 weeks
Full Information
NCT ID
NCT03153540
First Posted
March 1, 2017
Last Updated
February 14, 2022
Sponsor
University of British Columbia
1. Study Identification
Unique Protocol Identification Number
NCT03153540
Brief Title
Transcranial Magnetic Stimulation in Nonfluent/Agrammatic Variant Primary Progressive Aphasia
Official Title
A Randomized, Double-blinded, Sham-controlled Cross-over Study of Theta-burst Transcranial Magnetic Stimulation in Nonfluent/Agrammatic Variant Primary Progressive Aphasia
Study Type
Interventional
2. Study Status
Record Verification Date
February 2022
Overall Recruitment Status
Terminated
Why Stopped
Lack of recruitment
Study Start Date
September 1, 2018 (Actual)
Primary Completion Date
February 14, 2022 (Actual)
Study Completion Date
February 14, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of British Columbia
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
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 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Progressive Nonfluent Aphasia
Keywords
Aphasia, Agrammatism, Frontotemporal Dementia, Tauopathies, Neurodegenerative Diseases, Language Disorders, Frontotemporal Lobar Degeneration
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
2 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Active iTBS
Arm Type
Active Comparator
Arm Description
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).
Arm Title
Sham iTBS
Arm Type
Sham Comparator
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
Active iTBS
Intervention Description
Intermittent theta burst transcranial magnetic stimulation
Intervention Type
Device
Intervention Name(s)
Sham iTBS
Intervention Description
Sham intervention
Primary Outcome Measure Information:
Title
Incidence of treatment-emergent adverse events
Description
Safety will be measured by incidence of treatment-emergent adverse events
Time Frame
6 weeks
Title
Tolerability levels according to the daily Comfort Rating Questionnaire (CRQ)
Description
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.
Time Frame
6 weeks
Title
Drop out rate
Description
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.
Time Frame
6 weeks
Secondary Outcome Measure Information:
Title
Changes in the Verb and Object Naming Test score
Description
Verb and Object Naming Test score at baseline and at 2, 4, and 6 weeks
Time Frame
6 weeks
Title
Changes in the Make a Sentence Test score
Description
Make a Sentence Test score at baseline and at 2, 4, and 6 weeks
Time Frame
6 weeks
Title
Changes in the Sentence Comprehension Test score
Description
Sentence Comprehension Test score at baseline and at 2, 4, and 6 weeks
Time Frame
6 weeks
Title
Changes in the Apraxia of Speech Rating Scale score
Description
Apraxia of Speech Rating Scale score at baseline and at 6 weeks
Time Frame
6 weeks
Title
Changes in the Clinical Global Impression of Change score
Description
Clinical Global Impression of Change score at baseline and at 2, 4, and 6 weeks
Time Frame
6 weeks
Title
Changes in the Progressive Aphasia Severity Scale rating
Description
Progressive Aphasia Severity Scale rating at baseline and at 6 weeks
Time Frame
6 weeks
Title
Changes in the Western Aphasia Battery rating
Description
Western Aphasia Battery rating at baseline and at 6 weeks
Time Frame
6 weeks
Title
Changes in the Montreal Cognitive Assessment Battery score
Description
Montreal Cognitive Assessment Battery score at baseline and at 6 weeks
Time Frame
6 weeks
Title
Changes in the Frontal Assessment Battery score
Description
Frontal Assessment Battery score at baseline and at 6 weeks
Time Frame
6 weeks
Title
Changes in the whole-brain functional connectivity measured using functional Magnetic Resonance Imaging (MRI)
Description
fMRI at baseline and at 2 and 6 weeks
Time Frame
6 weeks
Title
Changes in the brain cortical blood oxygenation measured using functional Near Infrared Spectroscopy (fNIRS)
Description
fNIRS at baseline and at 2, 4, and 6 weeks
Time Frame
6 weeks
Title
Changes in the brain cortical electrical activity measured using quantitative electroencephalography (EEG)
Description
EEG at baseline and at 2, 4, and 6 weeks
Time Frame
6 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fidel Vila-Rodriguez, MD
Organizational Affiliation
University of British Columbia
Official's Role
Principal Investigator
Facility Information:
Facility Name
Non-Invasive Neurostimulation Therapies lab, University of British Columbia
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6T2A1
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Transcranial Magnetic Stimulation in Nonfluent/Agrammatic Variant Primary Progressive Aphasia
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