rTMS as a Treatment for PPA
| Status: | Recruiting |
|---|---|
| Conditions: | Neurology, Neurology |
| Therapuetic Areas: | Neurology |
| Healthy: | No |
| Age Range: | 18 - 90 |
| Updated: | 1/23/2019 |
| Start Date: | March 1, 2019 |
| End Date: | January 1, 2022 |
| Contact: | Mark C Eldaief, M.D. |
| Email: | meldaief@mgh.harvard.edu |
| Phone: | (617) 726-1728 |
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.
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.
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.
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.
Inclusion Criteria:
1. 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.
2. Patients must have at least mild to moderate language impairment.
3. Patients must be native English speakers.
4. Patients must have a study partner (e.g. spouse, sibling or adult child) who can
accompany them to every study visit.
Exclusion Criteria:
1. Any history of seizures, unexplained loss of consciousness or a first-degree family
member with epilepsy.
2. 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).
3. 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.
4. Magnetic Resonance Imaging (MRI) evidence of significant cerebrovascular disease,
hydrocephalus or the presence of a space-occupying intra-cranial mass.
5. 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.
6. 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.
We found this trial at
1
site
185 Cambridge Street
Boston, Massachusetts 02114
Boston, Massachusetts 02114
617-724-5200
Phone: 617-726-1728
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