rTMS as a Treatment for PPA (NCT03406429) | Clinical Trial Compass
CompletedEarly Phase 1
rTMS as a Treatment for PPA
United States12 participantsStarted 2019-12-01
Plain-language 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. 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.
Who can participate
Age range18 Years – 90 Years
SexALL
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Inclusion criteria
✓. 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.
Exclusion criteria
✕. 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.
What they're measuring
1
Language Assessment Battery
Timeframe: At the beginning and end of each rTMS block.
2
MRI Imaging
Timeframe: At the baseline visit and at the end of each rTMS block.
✕. 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.