search
Back to results

TMS for the Treatment of Primary Progressive Aphasia

Primary Purpose

Logopenic Variant Primary Progressive Aphasia, Non-fluent Variant Primary Progressive Aphasia, Semantic Variant Primary Progressive Aphasia

Status
Recruiting
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
ACTIVE rTMS
SHAM rTMS
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Logopenic Variant Primary Progressive Aphasia

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Patients, age 18-90, who carry a diagnosis of either the logopenic (lvPPA), agrammatic non-fluent (nfvPPA) or semantic (svPPA) 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.

    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.

  5. 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.

Sites / Locations

  • Massachusetts General HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

PPA patients

Arm Description

All study participants will carry a diagnosis of Primary Progressive Aphasia (PPA), either the logopenic, the non-fluent variant or the semantic variant. All participants will receive the same study interventions in a within-subject crossover design.

Outcomes

Primary Outcome Measures

Changes in Language
This will include observed changes in speech production as a result of the stimulation.
Changes in Brain Network Connectivity
This will include observed changes in resting-state functional connectivity as a result of the stimulation.

Secondary Outcome Measures

Full Information

First Posted
December 2, 2019
Last Updated
October 17, 2023
Sponsor
Massachusetts General Hospital
Collaborators
National Institute on Deafness and Other Communication Disorders (NIDCD)
search

1. Study Identification

Unique Protocol Identification Number
NCT04188067
Brief Title
TMS for the Treatment of Primary Progressive Aphasia
Official Title
TMS in Primary Progressive Aphasia: Modulation of Brain Networks and Language
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 1, 2022 (Actual)
Primary Completion Date
January 31, 2025 (Anticipated)
Study Completion Date
January 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
National Institute on Deafness and Other Communication Disorders (NIDCD)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Primary Progressive Aphasia (PPA) is a progressive syndrome in the family of Alzheimer's disease and related disorders involving devastating language impairments caused by selective neurodegeneration of the brain's language network. Unfortunately, there is no treatment for PPA. An exciting possibility for treatment is non-invasive repetitive transcranial brain stimulation (rTMS), which induces electric currents in degenerating brain networks, making them in some cases more efficient. 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 and in patients with Alzheimer's disease. Further, in a sham controlled study, Cotelli and colleagues demonstrated that in a group of 10 non-fluent PPA patients, high frequency rTMS over the left and right dlPFC improved the percent of correct responses for action naming. When rTMS was applied for five consecutive days in a sham controlled single case study, Finocchiaro and colleagues showed lasting improvements in language (up to 1 week) in a patient with non-fluent PPA. Trebbastoni and colleagues further showed the same lasting improvements in language (up to 1 week) in a patient with logopenic PPA. Recently, in a sham controlled single case study, Bereau and colleagues applied a more intense rTMS protocol for ten consecutive days and demonstrated significant linguistic improvements in a logopenic PPA patient that lasted for 1 month. These studies have contributed valuable insights into the potential use of rTMS in treating the language symptoms of PPA patients.
Detailed Description
30 patients with a confirmed diagnosis of PPA (non-fluent PPA, logopenic PPA or semantic PPA) (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 4 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 21 study visits. Greater than 21 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 dorsolateral prefrontal cortex: 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 10 days (Monday through Friday). Neuropsychological testing, including thorough language evaluations, will be done before treatment, after day 1 and day 10 of rTMS treatment. Repeat MRI imaging will be performed after day 1 and day 10 of rTMS treatment. rTMS visit durations will be as follows: Monday (day 1) visit will last approximately 3-4 hours. Tuesday, Wednesday and Thursday and Friday visits (day 2 to day 9) will last approximately 1-2 hours. Friday visit (day 10) will last approximately 5 hours.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Logopenic Variant Primary Progressive Aphasia, Non-fluent Variant Primary Progressive Aphasia, Semantic Variant Primary Progressive Aphasia

7. Study Design

Primary Purpose
Other
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Within-subject crossover design
Masking
None (Open Label)
Masking Description
Through use of SHAM rTMS stimulation
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
PPA patients
Arm Type
Experimental
Arm Description
All study participants will carry a diagnosis of Primary Progressive Aphasia (PPA), either the logopenic, the non-fluent variant or the semantic variant. All participants will receive the same study interventions in a within-subject crossover design.
Intervention Type
Device
Intervention Name(s)
ACTIVE rTMS
Intervention Description
All study participants will receive one block of ACTIVE rTMS. Each block will consist of daily sessions of active rTMS delivered to the left dorsolateral prefrontal cortex over ten days (Monday through Friday).
Intervention Type
Device
Intervention Name(s)
SHAM rTMS
Intervention Description
All study participants will receive one block of SHAM rTMS. Each block will consist of daily sessions of SHAM rTMS delivered to the left dorsolateral prefrontal cortex over ten days (Monday through Friday).
Primary Outcome Measure Information:
Title
Changes in Language
Description
This will include observed changes in speech production as a result of the stimulation.
Time Frame
Baseline and post treatment Day 10
Title
Changes in Brain Network Connectivity
Description
This will include observed changes in resting-state functional connectivity as a result of the stimulation.
Time Frame
Baseline and post treatment Day 10

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients, age 18-90, who carry a diagnosis of either the logopenic (lvPPA), agrammatic non-fluent (nfvPPA) or semantic (svPPA) 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. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Alexandra Touroutoglou, PhD
Phone
6176436348
Email
atouroutoglou@mgh.harvard.edu
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02129
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexandra Touroutoglou, PhD
Phone
617-643-6348
Email
atouroutoglou@mgh.harvard.edu

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
22435956
Citation
Cotelli M, Manenti R, Alberici A, Brambilla M, Cosseddu M, Zanetti O, Miozzo A, Padovani A, Miniussi C, Borroni B. Prefrontal cortex rTMS enhances action naming in progressive non-fluent aphasia. Eur J Neurol. 2012 Nov;19(11):1404-12. doi: 10.1111/j.1468-1331.2012.03699.x. Epub 2012 Mar 21.
Results Reference
background
PubMed Identifier
17182394
Citation
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.
Results Reference
background
PubMed Identifier
23122915
Citation
Trebbastoni A, Raccah R, de Lena C, Zangen A, Inghilleri M. Repetitive deep transcranial magnetic stimulation improves verbal fluency and written language in a patient with primary progressive aphasia-logopenic variant (LPPA). Brain Stimul. 2013 Jul;6(4):545-53. doi: 10.1016/j.brs.2012.09.014. Epub 2012 Oct 24.
Results Reference
background
PubMed Identifier
27344155
Citation
Bereau M, Magnin E, Nicolier M, Berthet L, Dariel E, Ferreira S, Sylvestre G, Monnin J, Chopard G, Bouladour H, Vandel P, Haffen E. Left Prefrontal Repetitive Transcranial Magnetic Stimulation in a Logopenic Variant of Primary Progressive Aphasia: A Case Report. Eur Neurol. 2016;76(1-2):12-8. doi: 10.1159/000447399. Epub 2016 Jun 25.
Results Reference
background

Learn more about this trial

TMS for the Treatment of Primary Progressive Aphasia

We'll reach out to this number within 24 hrs