Transcranial Magnetic Stimulation and Constraint Induced Language Therapy for Alzheimer Disease

January 31, 2024 updated by: H. Branch Coslett, University of Pennsylvania

A Phase II, Randomized, Blinded Study of Transcranial Magnetic Stimulation and Constraint Induced Language Therapy for the Treatment of Chronic Aphasia - Alzheimer Disease Sub-study

Impaired verbal communication is a cardinal symptom of Alzheimer Disease (AD) and the source of enormous distress and disability. Effective therapies for this deficit are lacking. In light of the emerging literature demonstrating that Transcranial Magnetic Stimulation (TMS) improves general cognition in subjects with Alzheimer Disease (AD), the investigators propose to study the effectiveness of TMS as a therapy for impaired verbal communication. The hypothesis to be tested is that TMS combined with Constraint Induced Language Therapy (CILT) improves verbal communication more than sham TMS and CILT. A second aim is to use state-of-the-art neuroimaging to understand the mechanisms underlying any beneficial effect of the treatment.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

TMS is a technique by which a brief electrical current is induced in brain tissue causing a brief suppression of the excitability of the underlying tissue; the technique, which was introduced in the 1980s and has been extensively used around the world, has been shown to transiently improve or disrupt specific cognitive operations. To achieve this end, a coil is positioned against the subject's head. The delivery of a single pulse begins with the discharge of current from a capacitor into a circular or figure-of-eight coil; this electrical current generates a brief magnetic field of up to 2.2 Tesla. As the pulse of electricity has a rise time of 0.2 ms. and a duration of 1 ms., the magnetic field changes in intensity quite rapidly. Because the magnetic field passes freely through the scalp, skull, and meninges, the flux in the magnetic field induces a small electric field in the brain that transiently alters neural activity.

TMS may be delivered in a variety of ways. The investigators propose to use 10 Hz TMS; that is, TMS pulses will be delivered at a frequency of 10/second, for a total of 1200 pulses. Using the figure-of-eight coil to be employed here, TMS is thought to affect activity in approximately 1 cubic cm. of cortex. Many investigators have employed TMS for AD with a frequency of 10 Hz and most have delivered 1200 pulses per session.

The baseline phase will consist of 3 sessions, each lasting 1-2 hours depending on the stamina of the subject. The point of the baseline testing is to characterize the subject's language function. To that end, a number of standard language and neuropsychological tasks will be administered. These include the Western Aphasia Battery, Pyramids and Palm Trees test, Figural Fluency Test, word and non-word repetition tasks, spontaneous narrative production, CILT stimulus naming, and the Repeatable Battery for the Assessment of Neuropsychological Status. Additionally, during the baseline, subjects will undergo MRI of the brain or, if they have a contraindication to MRI, a CAT scan of the head. No contrast will be used.

In the treatment phase, there will be 10 TMS sessions over 2 consecutive weeks in which 30 two-second stimulation trains of 10 Hz TMS will be delivered every 30 seconds to the left inferior pars triangularis and to the left posterior superior left temporal gyrus at 100% motor threshold. There will be a total of 600 pulses to each site in each session for a total of 1200 pulses per session. Each TMS treatment session will be immediately followed by a 60-90 minute session of CILT.

There will be two 3-month post-treatment visits and two 6-month post-treatment visits in which the full battery of language and cognitive assessments will be repeated. Subjects who are able to undergo MRI scanning will have anatomic and fMRI scans at the first 6-month post-treatment visit.

The investigators will pair TMS with CILT which has been shown to have positive outcomes in post-stroke aphasia. CILT invokes use-dependent learning in communicative interactions by requiring spoken output and restricting use of alternative forms of communication, such as gestures. The investigators will use a dual card-matching task modeled after Maher et al. As in the original CILT design, the participant interacts verbally with a conversational partner (here, the speech language pathologist), in turn requesting a card of given description and complying with the partner's request. In this way, the treatment targets both production and comprehension. Moreover, as verbal targets increase in linguistic complexity across the protocol ("a ball", "throw a ball"; "Do you have a ball"?), a variety of lexical and phrasal structures are targeted. Studies of CILT have reported gains on multiple language behaviors, supporting its broad engagement of the language network.

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • A diagnosis of mild-moderate AD as defined by the National Institute of Aging - Alzheimer's Disease and Related Disorders Association criteria
  • Mild-moderate cognitive impairment, indicated by Mini-Mental Status Exam (MMSE) scores between 23 and 15 inclusive
  • Must be right handed as defined by the Edinburgh Handedness Inventory
  • Must be a native English speaker
  • Must be able to understand the nature of the study, and give informed consent

Exclusion Criteria:

  • History of stroke
  • History of seizure
  • History of any other significant neurologic disease (e.g., ALS)
  • Significant depression as defined by the Geriatric Depression Scale.
  • Any significant medical disorder that, in the view of the investigators, could threaten the subject's ability to complete the study (e.g., cancer, significant cardiac disease)
  • Any contraindications to TMS, including uncontrolled seizures, previous brain surgery, and history of tinnitus

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Active TMS
There will be 10 TMS sessions over 2 consecutive weeks in which 30 two-second stimulation trains of 10 Hz TMS will be delivered every 30 seconds to the left inferior pars triangularis and to the left posterior superior left temporal gyrus. Each TMS treatment session will be immediately followed by a 60-90 minute session of Constrained Induced Language Therapy (CILT).
Device: Active TMS
Active TMS will be delivered at 100% motor threshold
Behavioral: CILT
60-90 minutes of CILT will be administered during each treatment session
Other Names:
  • Constraint Induced Language Therapy
Sham Comparator: Sham TMS
There will be 10 TMS sessions over 2 consecutive weeks in which 30 two-second stimulation trains of 10 Hz sham TMS will be delivered every 30 seconds to the left inferior pars triangularis and to the left posterior superior left temporal gyrus. Sham TMS will be administered with a sham TMS coil that looks and sounds like the active coil but does not generate a magnetic field. Each TMS treatment session will be immediately followed by a 60-90 minute session of Constrained Induced Language Therapy (CILT).
Behavioral: CILT
60-90 minutes of CILT will be administered during each treatment session
Other Names:
  • Constraint Induced Language Therapy
Device: Sham TMS
Sham TMS will be administered

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in WAB-AQ
Time Frame: 6-months post-treatment
Overall change in Western Aphasia Battery - Aphasia Quotient (WAB-AQ) between the first baseline visit and the 6-month follow-up visit. WAB-AQ is measured on a scale from 0 to 100, with higher scores meaning greater language ability
6-months post-treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in PNT
Time Frame: 6-months post-treatment
Change in naming accuracy on the Philadelphia Naming Test (PNT) between the first baseline visit and the 6-month follow-up visit. PNT naming accuracy is measured as a percentage from 0% to 100% with higher percentages meaning better naming ability.
6-months post-treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pennsylvania

Collaborators

National Institutes of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)

Investigators

  • Principal Investigator: H. Branch Coslett, MD, University of Pennsylvania

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 19, 2020

Primary Completion (Estimated)

August 31, 2024

Study Completion (Estimated)

August 31, 2024

Study Registration Dates

First Submitted

July 17, 2020

First Submitted That Met QC Criteria

July 17, 2020

First Posted (Actual)

July 22, 2020

Study Record Updates

Last Update Posted (Estimated)

February 1, 2024

Last Update Submitted That Met QC Criteria

January 31, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 831532
  • R01DC016800-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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