Logopenic Variant Primary Progressive AphasiaEarly Phase 1NCT03406429
rTMS as a Treatment for PPA
A Early Phase 1 study testing Active rTMS in people with Logopenic Variant Primary Progressive Aphasia and Non-Fluent Primary Progressive Aphasia, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
Primary progressive aphasia (PPA) includes three variants. Two such variants, the non-fluent/agrammatic variant (nfvPPA) and the logopenic variant (lvPPA), are characterized by progressive word-finding difficulties and effortful speech. Efforts to slow or halt this progression have been largely unsuccessful. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Logopenic Variant Primary Progressive Aphasia, Non-Fluent Primary Progressive Aphasia
- What is being tested?
- Active rTMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Dec 2019to 1 Jan 2022
- Phase
- Early Phase 1
- 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 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients, age 18-90, who carry a diagnosis of either the logopenic (lvPPA) or agrammatic non-fluent (nfvPPA) variants of Primary Progressive Aphasia (PPA). Patients must have been observed for at least one year by a specialized clinician.
- Patients must have at least mild to moderate language impairment.
- Patients must be native English speakers.
- Patients must have a study partner (e.g. spouse, sibling or adult child) who can accompany them to every study visit.
Who cannot join
- Any history of seizures, unexplained loss of consciousness or a first-degree family member with epilepsy.
- Any history of significant co-occurring neurological illness unrelated to neurodegeneration associated with PPA (e.g. multiple sclerosis), or significant medical problems (e.g. poorly controlled diabetes/hypertension or cancer within 5 years).
- Active symptoms of major depressive disorder, bipolar disorder, schizophrenia, substance use disorder or significant premorbid intellectual disability according to Diagnostic Statistical Manual (DSM-5) criteria.
- Magnetic Resonance Imaging (MRI) evidence of significant cerebrovascular disease, hydrocephalus or the presence of a space-occupying intra-cranial mass.
- Contraindications to MRI or repetitive transcranial magnetic stimulation (rTMS) including: cardiac pacemaker or pacemaker wires, neurostimulators, implanted pumps, metal in the body (rods, plates, screws, shrapnel, dentures, intrauterine device), surgical aneurysm clips in the head, previous neurosurgery or cochlear implants.
- In line with published Massachusetts General Hospital (MGH) Institutional Review Board (IRB) guidelines for rTMS, pregnancy must be ruled out by urine ß-Human Chorionic Gonadotropin if answers to screening questions suggest that pregnancy is possible and if female participants are premenopausal and of child-bearing age. Subjects will not be able to enroll if they are breastfeeding.
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02129
About this study
Official title: Pilot Study of Repetitive Transcranial Magnetic Stimulation in Patients With Primary Progressive Aphasia.
Primary progressive aphasia (PPA) includes three variants. Two such variants, the non-fluent/agrammatic variant (nfvPPA) and the logopenic variant (lvPPA), are characterized by progressive word-finding difficulties and effortful speech. Efforts to slow or halt this progression have been largely unsuccessful. As such, there is a desperate need for novel treatment strategies in PPA.
Repetitive transcranial magnetic stimulation (rTMS) is a safe, non-invasive way of stimulating cortical targets in a focal and reproducible manner. Therapeutic benefits from rTMS have been demonstrated when it is applied in many sequential sessions. For example, repeated sessions of rTMS to left dorsolateral prefrontal cortex (dlPFC) is approved by the US Food and Drug administration as a treatment for major depressive disorder. With respect to language, high frequency rTMS increases the response rate for picture naming in healthy individuals. rTMS has also been shown to improve the number of correct naming responses in patients with Alzheimer's disease. Further, in a sham controlled study, Cotelli and colleagues demonstrated that in a group of 10 nfvPPA patients high frequency rTMS over the left and right dlPFC during object and action naming tasks improved the percent of correct responses for action, but not object naming. Finally, in a sham controlled single case study, Finocchiaro et al. applied high frequency rTMS to the left inferior mid-frontal gyrus for 3 sessions consisting of five consecutive days (treatment or sham). They found a significant and lasting improvement in the patient's performance on verb production when comparing active rTMS to sham rTMS or baseline. These studies have contributed valuable insights into the potential use of rTMS in treating the language symptoms of PPA patients.
Read the detailed description
15-20 patients with a confirmed diagnosis of either nfvPPA or lvPPA (made by a specialized clinician) will be recruited. Patients must have a mild to moderate language impairment and must be native English speakers. Exclusion criteria include contraindications to receiving Magnetic Resonance Imaging (MRI) scanning or rTMS (e.g. metallic or electromagnetically activated implants, cranial mass lesions, surgical aneurysm clips), the presence of significant medical, neurological or psychiatric co-morbid symptoms and patients without study partners.
It will take approximately 2 weeks to complete this research study, but the exact timing will vary according to patient, investigator and equipment availability. Each patient will have a total of up to 11 study visits. Greater than 11 visits may take place in the event that patients' language improves significantly following rTMS in order to test the sustainability of the improvement. Visits will take place at the MGH Martinos Center for Biomedical Imaging.
The first visit (lasting 3-4 hours) will include obtainment of informed consent, baseline assessments, and a baseline MRI scan (which will be used for subsequent rTMS targeting). After this, patients will return for two blocks of 20Hz rTMS to left dlpfc: one in which they receive active rTMS and one in which they receive sham rTMS. Both active and sham rTMS will be delivered as high frequency stimulation (20 hertz, 20Hz). To accomplish this, an rTMS coil capable of delivering active or sham stimulation will be employed. Order of active and sham blocks will be counterbalanced across participants. During each block rTMS (active or sham) will be administered daily for 5 days (Monday through Friday). Neuropsychological testing, including thorough language evaluations, will be done before and after each block of rTMS. Repeat MRI imaging will be performed at the end of each of the two blocks. rTMS visit durations will be as follows: Monday visits will last approximately 3-4 hours, Tuesday, Wednesday and Thursday visits will last approximately 1-2 hours and Friday visits will last approximately 5 hours.
- Being tested
- Active rTMS, SHAM rTMS
- Keywords
- rTMS, PPA
- Medical subject headings
- Primary Progressive Nonfluent Aphasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active rTMSDevice
All study participants will receive one block of active rTMS. Each block will consist of daily sessions of 20Hz active rTMS delivered to the left dorsolateral prefrontal cortex (dlPFC) over five days (Monday through Friday).
SHAM rTMSDevice
All study participants will receive one block of SHAM rTMS. Each block will consist of daily sessions of 20Hz SHAM rTMS delivered to the left dorsolateral prefrontal cortex (dlPFC) over five days (Monday through Friday).
| Study group | Role | What they receive |
|---|---|---|
| PPA patients | Experimental | All study participants will carry a diagnosis of Primary Progressive Aphasia (PPA), either the logopenic or the non-fluent variant. All participants will receive the same study interventions in a within-subject crossover design. Receives: Device: Active rTMS; Device: SHAM rTMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Language Assessment Battery
This will include tests of speech production, confrontation naming, sentence completion.
Measured: At the beginning and end of each rTMS block.
MRI Imaging
This will include observed changes in resting-state functional connectivity and cortical thickness occurring as a result of the stimulation.
Measured: At the baseline visit and at the end of each rTMS block.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2018
- Study start1 Dec 2019
- Primary completion1 Jan 2022
- Study completion1 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Logopenic Variant Primary Progressive AphasiaStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe 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
- Early Phase 1
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Within-subject crossover design
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mark C. Eldaief, MD, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03406429
- Sponsor's protocol ID
- 2017P002319
- Status last verified
- Apr 2022
- First submitted
- 20 Dec 2017
- Last updated
- 7 Apr 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Finocchiaro C, Maimone M, Brighina F, Piccoli T, Giglia G, Fierro B. A case study of Primary Progressive Aphasia: improvement on verbs after rTMS treatment. Neurocase. 2006 Dec;12(6):317-21. doi: 10.1080/13554790601126203.
PubMed 17182394Cotelli M, Manenti R, Petesi M, Brambilla M, Cosseddu M, Zanetti O, Miniussi C, Padovani A, Borroni B. Treatment of primary progressive aphasias by transcranial direct current stimulation combined with language training. J Alzheimers Dis. 2014;39(4):799-808. doi: 10.3233/JAD-131427.
PubMed 24296814
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Repetitive Transcranial Magnetic Stimulation in Patients With Primary Progressive Aphasia.
- ClinicalTrials.gov ID
- NCT03406429
- Acronym / sponsor ID
- 2017P002319
- Keywords
- rTMS, PPA
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- 1 Dec 2019 (actual)
- Primary completion
- 1 Jan 2022 (actual)
- Study completion
- 1 Jan 2022 (actual)
- First posted
- 23 Jan 2018 (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.
Primary progressive aphasia (PPA) includes three variants. Two such variants, the non-fluent/agrammatic variant (nfvPPA) and the logopenic variant (lvPPA), are characterized by progressive word-finding difficulties and effortful speech. Efforts to slow or halt this progression have been largely unsuccessful. As such, there is a desperate need for novel treatment strategies in PPA.
Repetitive transcranial magnetic stimulation (rTMS) is a safe, non-invasive way of stimulating cortical targets in a focal and reproducible manner. Therapeutic benefits from rTMS have been demonstrated when it is applied in many sequential sessions. For example, repeated sessions of rTMS to left dorsolateral prefrontal cortex (dlPFC) is approved by the US Food and Drug administration as a treatment for major depressive disorder. With respect to language, high frequency rTMS increases the response rate for picture naming in healthy individuals. rTMS has also been shown to improve the number of correct naming responses in patients with Alzheimer's disease. Further, in a sham controlled study, Cotelli and colleagues demonstrated that in a group of 10 nfvPPA patients high frequency rTMS over the left and right dlPFC during object and action naming tasks improved the percent of correct responses for action, but not object naming. Finally, in a sham controlled single case study, Finocchiaro et al. applied high frequency rTMS to the left inferior mid-frontal gyrus for 3 sessions consisting of five consecutive days (treatment or sham). They found a significant and lasting improvement in the patient's performance on verb production when comparing active rTMS to sham rTMS or baseline. These studies have contributed valuable insights into the potential use of rTMS in treating the language symptoms of PPA patients.
Detailed description
15-20 patients with a confirmed diagnosis of either nfvPPA or lvPPA (made by a specialized clinician) will be recruited. Patients must have a mild to moderate language impairment and must be native English speakers. Exclusion criteria include contraindications to receiving Magnetic Resonance Imaging (MRI) scanning or rTMS (e.g. metallic or electromagnetically activated implants, cranial mass lesions, surgical aneurysm clips), the presence of significant medical, neurological or psychiatric co-morbid symptoms and patients without study partners.
It will take approximately 2 weeks to complete this research study, but the exact timing will vary according to patient, investigator and equipment availability. Each patient will have a total of up to 11 study visits. Greater than 11 visits may take place in the event that patients' language improves significantly following rTMS in order to test the sustainability of the improvement. Visits will take place at the MGH Martinos Center for Biomedical Imaging.
The first visit (lasting 3-4 hours) will include obtainment of informed consent, baseline assessments, and a baseline MRI scan (which will be used for subsequent rTMS targeting). After this, patients will return for two blocks of 20Hz rTMS to left dlpfc: one in which they receive active rTMS and one in which they receive sham rTMS. Both active and sham rTMS will be delivered as high frequency stimulation (20 hertz, 20Hz). To accomplish this, an rTMS coil capable of delivering active or sham stimulation will be employed. Order of active and sham blocks will be counterbalanced across participants. During each block rTMS (active or sham) will be administered daily for 5 days (Monday through Friday). Neuropsychological testing, including thorough language evaluations, will be done before and after each block of rTMS. Repeat MRI imaging will be performed at the end of each of the two blocks. rTMS visit durations will be as follows: Monday visits will last approximately 3-4 hours, Tuesday, Wednesday and Thursday visits will last approximately 1-2 hours and Friday visits will last approximately 5 hours.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Within-subject crossover design
| Arm | Type | Receives |
|---|---|---|
| PPA patients | Experimental | Device: Active rTMS, Device: SHAM rTMSAll study participants will carry a diagnosis of Primary Progressive Aphasia (PPA), either the logopenic or the non-fluent variant. All participants will receive the same study interventions in a within-subject crossover design. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients, age 18-90, who carry a diagnosis of either the logopenic (lvPPA) or agrammatic non-fluent (nfvPPA) variants of Primary Progressive Aphasia (PPA). Patients must have been observed for at least one year by a specialized clinician.
- Patients must have at least mild to moderate language impairment.
- Patients must be native English speakers.
- Patients must have a study partner (e.g. spouse, sibling or adult child) who can accompany them to every study visit.
Key exclusion criteria (6 listed)
- Any history of seizures, unexplained loss of consciousness or a first-degree family member with epilepsy.
- Any history of significant co-occurring neurological illness unrelated to neurodegeneration associated with PPA (e.g. multiple sclerosis), or significant medical problems (e.g. poorly controlled diabetes/hypertension or cancer within 5 years).
- Active symptoms of major depressive disorder, bipolar disorder, schizophrenia, substance use disorder or significant premorbid intellectual disability according to Diagnostic Statistical Manual (DSM-5) criteria.
- Magnetic Resonance Imaging (MRI) evidence of significant cerebrovascular disease, hydrocephalus or the presence of a space-occupying intra-cranial mass.
- Contraindications to MRI or repetitive transcranial magnetic stimulation (rTMS) including: cardiac pacemaker or pacemaker wires, neurostimulators, implanted pumps, metal in the body (rods, plates, screws, shrapnel, dentures, intrauterine device), surgical aneurysm clips in the head, previous neurosurgery or cochlear implants.
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 rTMSAll study participants will receive one block of active rTMS. Each block will consist of daily sessions of 20Hz active rTMS delivered to the left dorsolateral prefrontal cortex (dlPFC) over five days (Monday through Friday). | Device | PPA patients |
| SHAM rTMSAll study participants will receive one block of SHAM rTMS. Each block will consist of daily sessions of 20Hz SHAM rTMS delivered to the left dorsolateral prefrontal cortex (dlPFC) over five days (Monday through Friday). | Device | PPA patients |
Primary outcome
Language Assessment Battery
Time frame: At the beginning and end of each rTMS block.
This will include tests of speech production, confrontation naming, sentence completion.
MRI Imaging
Time frame: At the baseline visit and at the end of each rTMS block.
This will include observed changes in resting-state functional connectivity and cortical thickness occurring as a result of the stimulation.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2022.
- Background: PubMed 17182394Finocchiaro C, Maimone M, Brighina F, Piccoli T, Giglia G, Fierro B. A case study of Primary Progressive Aphasia: improvement on verbs after rTMS treatment. Neurocase. 2006 Dec;12(6):317-21. doi: 10.1080/13554790601126203.
- Background: PubMed 24296814Cotelli M, Manenti R, Petesi M, Brambilla M, Cosseddu M, Zanetti O, Miniussi C, Padovani A, Borroni B. Treatment of primary progressive aphasias by transcranial direct current stimulation combined with language training. J Alzheimers Dis. 2014;39(4):799-808. doi: 10.3233/JAD-131427.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Active rTMS in people with Logopenic Variant Primary Progressive Aphasia and Non-Fluent Primary Progressive Aphasia, run by Massachusetts General Hospital at 1 site in United States.
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 4 inclusion and 6 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: finished, as of the sponsor's last update on 7 Apr 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 United States. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Language Assessment Battery (time frame: At the beginning and end of each rTMS block.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03406429, which also lists 2 linked publications.
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 7 Apr 2022.