rTMS as a Treatment for PPA

NCT03406429 | Completed Early Phase 1 FDA Device

• 1 other identifier: 2017P002319
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Logopenic Variant Primary Progressive Aphasia; Non-Fluent Primary Progressive Aphasia

Keywords

rTMS; PPA

Outcome Measures

Primary Outcomes (2)

• Language Assessment Battery

  This will include tests of speech production, confrontation naming, sentence completion.

  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.

  At the baseline visit and at the end of each rTMS block.

Study Arms (1)

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.

Device: Active rTMS; Device: SHAM rTMS

Interventions

Active rTMS DEVICE

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).

PPA patients

SHAM rTMS DEVICE

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).

PPA patients

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02129, United States

Location

Related Publications (2)

• 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.

  PMID: 17182394 BACKGROUND

• Cotelli 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.

  PMID: 24296814 BACKGROUND

MeSH Terms

Conditions

Primary Progressive Nonfluent Aphasia

Condition Hierarchy (Ancestors)

Aphasia, Primary Progressive; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Frontotemporal Lobar Degeneration; TDP-43 Proteinopathies; Neurodegenerative Diseases; Aphasia; Speech Disorders; Language Disorders; Communication Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Through use of SHAM rTMS stimulation
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Neurology

Model Details: Within-subject crossover design

Study Record Dates

• First Submitted: December 20, 2017
• First Posted: January 23, 2018
• Study Start: December 1, 2019
• Primary Completion: January 1, 2022
• Study Completion: January 1, 2022
• Last Updated: April 7, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)