Primary Progressive Nonfluent AphasiaNCT03153540
Transcranial Magnetic Stimulation in Nonfluent/Agrammatic Variant Primary Progressive Aphasia
A study testing Active iTBS in people with Primary Progressive Nonfluent Aphasia, run by University of British Columbia at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Primary Progressive Nonfluent Aphasia
- What is being tested?
- Active iTBS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2 participants
- Where
- 1 siteCanada
- Study dates
- 1 Sep 2018to 14 Feb 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
- Does not pass the TMS adult safety screening (TASS) questionnaire (e.g. has an intracranial implant)
- Severe claustrophobia.
- Cardiac pacemakers or ferromagnetic implants.
- Pregnant women.
Trial locations and contacts
1 site in 1 country.
Canada1 site
Non-Invasive Neurostimulation Therapies lab, University of British Columbia
Vancouver, British Columbia, V6T2A1
About this study
Official title: A Randomized, Double-blinded, Sham-controlled Cross-over Study of Theta-burst Transcranial Magnetic Stimulation in Nonfluent/Agrammatic Variant Primary Progressive Aphasia
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.
Read the 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.
- Conditions
- Primary Progressive Nonfluent Aphasia
- Being tested
- Active iTBS, Sham iTBS
- Keywords
- Aphasia, Agrammatism, Frontotemporal Dementia, Tauopathies, Neurodegenerative Diseases, Language Disorders, Frontotemporal Lobar Degeneration
- Medical subject headings
- Primary Progressive Nonfluent Aphasia, Aphasia, Aphasia, Broca, Frontotemporal Dementia, Tauopathies, Neurodegenerative Diseases, Language Disorders, Frontotemporal Lobar Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active iTBSDevice
Intermittent theta burst transcranial magnetic stimulation
Sham iTBSDevice
Sham intervention
| Study group | Role | What they receive |
|---|---|---|
| Active iTBS | Active comparator | 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). Receives: Device: Active iTBS |
| Sham iTBS | Sham comparator | 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. Receives: Device: Sham iTBS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of treatment-emergent adverse events
Safety will be measured by incidence of treatment-emergent adverse events
Measured: 6 weeks
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.
Measured: 6 weeks
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.
Measured: 6 weeks
Secondary outcomes (12)
Changes in the Verb and Object Naming Test score
Verb and Object Naming Test score at baseline and at 2, 4, and 6 weeks
Measured: 6 weeks
Changes in the Make a Sentence Test score
Make a Sentence Test score at baseline and at 2, 4, and 6 weeks
Measured: 6 weeks
Changes in the Sentence Comprehension Test score
Sentence Comprehension Test score at baseline and at 2, 4, and 6 weeks
Measured: 6 weeks
Changes in the Apraxia of Speech Rating Scale score
Apraxia of Speech Rating Scale score at baseline and at 6 weeks
Measured: 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
Measured: 6 weeks
Changes in the Progressive Aphasia Severity Scale rating
Progressive Aphasia Severity Scale rating at baseline and at 6 weeks
Measured: 6 weeks
Changes in the Western Aphasia Battery rating
Western Aphasia Battery rating at baseline and at 6 weeks
Measured: 6 weeks
Changes in the Montreal Cognitive Assessment Battery score
Montreal Cognitive Assessment Battery score at baseline and at 6 weeks
Measured: 6 weeks
Changes in the Frontal Assessment Battery score
Frontal Assessment Battery score at baseline and at 6 weeks
Measured: 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
Measured: 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
Measured: 6 weeks
Changes in the brain cortical electrical activity measured using quantitative electroencephalography (EEG)
EEG at baseline and at 2, 4, and 6 weeks
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2017
- Study start1 Sep 2018
- Primary completion14 Feb 2022
- Study completion14 Feb 2022
Why it stopped: Lack of recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Progressive Nonfluent AphasiaStudies of the same condition, open and under way.
- More trials run by University of British ColumbiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Fidel Vila-Rodriguez, University of British Columbia
- Investigators
- Fidel Vila-Rodriguez, MD, Principal investigator, University of British Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03153540
- Sponsor's protocol ID
- H16-01327
- Status last verified
- Feb 2022
- First submitted
- 1 Mar 2017
- Last updated
- 3 Mar 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blinded, Sham-controlled Cross-over Study of Theta-burst Transcranial Magnetic Stimulation in Nonfluent/Agrammatic Variant Primary Progressive Aphasia
- ClinicalTrials.gov ID
- NCT03153540
- Acronym / sponsor ID
- H16-01327
- Conditions
- Primary Progressive Nonfluent Aphasia
- Keywords
- Aphasia, Agrammatism, Frontotemporal Dementia, Tauopathies, Neurodegenerative Diseases, Language Disorders, Frontotemporal Lobar Degeneration
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of recruitment
- Enrolment
- 2 participants (actual)
- Lead sponsor
- University of British ColumbiaUniversity, hospital or other
- Study start
- 1 Sep 2018 (actual)
- Primary completion
- 14 Feb 2022 (actual)
- Study completion
- 14 Feb 2022 (actual)
- First posted
- 15 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active iTBS | Active comparator | Device: Active iTBSDevice: 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). |
| Sham iTBS | Sham comparator | Device: Sham iTBSDevice: 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. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Active iTBSIntermittent theta burst transcranial magnetic stimulation | Device | Active iTBS |
| Sham iTBSSham intervention | Device | Sham iTBS |
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.
12 secondary outcomes
Changes in the Verb and Object Naming Test score
Time frame: 6 weeks
Changes in the Make a Sentence Test score
Time frame: 6 weeks
Changes in the Sentence Comprehension Test score
Time frame: 6 weeks
Changes in the Apraxia of Speech Rating Scale score
Time frame: 6 weeks
Changes in the Clinical Global Impression of Change score
Time frame: 6 weeks
Changes in the Progressive Aphasia Severity Scale rating
Time frame: 6 weeks
Changes in the Western Aphasia Battery rating
Time frame: 6 weeks
Changes in the Montreal Cognitive Assessment Battery score
Time frame: 6 weeks
Changes in the Frontal Assessment Battery score
Time frame: 6 weeks
Changes in the whole-brain functional connectivity measured using functional Magnetic Resonance Imaging (MRI)
Time frame: 6 weeks
Changes in the brain cortical blood oxygenation measured using functional Near Infrared Spectroscopy (fNIRS)
Time frame: 6 weeks
Changes in the brain cortical electrical activity measured using quantitative electroencephalography (EEG)
Time frame: 6 weeks
Results and safety
The study was stopped early (reason given: Lack of recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Fidel Vila-Rodriguez, MD principal investigator
University of British Columbia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active iTBS in people with Primary Progressive Nonfluent Aphasia, run by University of British Columbia at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Lack of recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of treatment-emergent adverse events (time frame: 6 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2022.