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Effect of Repetitive Transcranial Magnetic Stimulation on Language in Alzheimer's Disease

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gayatri Devi, MD, The New York Memory Services
ClinicalTrials.gov Identifier:
NCT00814697
First received: December 24, 2008
Last updated: January 8, 2014
Last verified: January 2014
  Purpose

The investigators wish to investigate the efficacy of targeted repetitive transcranial magnetic stimulation (rTMS) on expressive language in patients with Alzheimer's disease (AD). In rTMS, magnetic pulses are used to noninvasively stimulate focal areas of cortex of about a square centimeter in area. rTMS has been approved in the United States for the diagnosis of peripheral nerve conditions.

Depending on the frequency of stimulation, rTMS can preferentially stimulate or inhibit cortical areas. In stroke rehabilitation, for example, inhibition of the contralateral, uninvolved hemisphere by low frequency rTMS has improved movement of the affected limbs because of less aberrant inhibition of the affected hemisphere by the healthy hemisphere. The effects of rTMS has also been investigated and found to be useful in treating refractory depression and depression in Parkinson's disease. In addition, rTMS has improved naming in patients with Alzheimer's disease and has improved cognitive abilities and memory in non-demented older adults. Two studies found that rTMS improved aphasia in patients with stroke. While these studies are small, a review of the literature suggests that there may be a beneficial role for rTMS in patients with chronic neurological conditions. In addition, rTMS appears to be well tolerated, with transient headaches being the most common side effect.

In this small open label study, the investigators wish to investigate the usefulness of bilateral stimulation of the brain region termed the dorsolateral prefrontal cortex (DLPFC) in patients with AD who have naming and language deficits.


Condition Intervention Phase
Alzheimer's Disease
Aphasia
Dementia
Device: Repetitive Transcranial Magnetic Coil Stimulation (rTMS)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open-label, Exploratory Study of the Efficacy of Repetitive Transcranial Magnetic Stimulation on Naming and Verbal Fluency in Patients With Alzheimer's Disease With Functional Imaging Correlates

Resource links provided by NLM:


Further study details as provided by The New York Memory Services:

Primary Outcome Measures:
  • Cognitive Assessment Task Scores Before, During and After rTMS. [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

    Cognitive assessment tasks - Boston Diagnostic Aphasia Examination (BDAE), CFL Category naming (CFL), Mini-Mental State Examination (MMSE) - were administered and scored according to standard procedures before, during and 4 weeks after rTMS.

    Higher scores are associated with better cognition; No absolute cut-offs were used here as the outcomes were not categorically assessed.

    Total possible score ranges by test, lowest to highest:

    BDAE - 0 to 15 CFL - 0 to 62 MMSE - 0 to 30 Full range data and means presented below represents range of scores at 4-weeks post-rTMS treatments.



Enrollment: 12
Study Start Date: December 2008
Study Completion Date: August 2012
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Transcranial Magnetic Stimulation
Repetitive Transcranial Magnetic Coil Stimulation (rTMS) treatment in Alzheimer's disease. The Magstim Rapid2 stimulator with a peak magnetic field of 0.5-3.5 Tesla at 100% output was used over the right and left dorsolateral prefrontal cortex. Patients received 4 sessions of rTMS over 2 weeks, lasting approximately 30 minutes, 2 consecutive days a week for 2 weeks.
Device: Repetitive Transcranial Magnetic Coil Stimulation (rTMS)
The first six patients were administered rTMS at 10Hz in 20 trains of 5 seconds with 20 second intervals between trains in each hemisphere. The total number of pulses for each session was set at 1000 pulses. The second six enrolled patients were administered rTMS at 15 Hz in 20 trains of 5 seconds with 25 second intervals between trains in each hemisphere.

Detailed Description:

Subjects for this study will be recruited from Dr. Devi's clinical practice. Eligible subjects must have a diagnosis of possible or probable Alzheimer's disease using NINCDS-ADRDA criteria. The patient and his or her legally authorized representative need to be available to sign the informed consent. The assent of the incapable subject will be obtained prior to enrolling the subject in the study.

Once informed consent and assent are obtained, the subject will have a functional magnetic resonance imaging (fMRI) scan of their brain anytime during the 2 weeks prior to the first study visit. At Visit 1, subjects will undergo a baseline battery of cognitive tests lasting approximately 30 minutes. Subsequently, the subject will undergo rTMS.

During the visit, Dr. Devi will locate the area of the brain to be stimulated and mark that area of the scalp with an indelible skin marker that will wash out over time. In addition, the subjects will be provided with ear plugs to use during stimulation. This process of locating the area to be stimulated will take about an hour and will occur once. Then rTMS will be started and this procedure will take approximately 20-30 minutes (please see the full protocol for a complete description of this process).

Each rTMS stimulation session will last for about 30 minutes, 2 consecutive days a week for 2 weeks. Both immediately prior to the onset of the first rTMS session, and just after the end of the fourth and final rTMS session, subjects will be tested on their cognitive and language skills. These two testing sessions will last 30 minutes each. Subjects will have another fMRI scan anytime during the 2 days after the fourth and final rTMS stimulation session.

Subjects will continue to receive usual care throughout the study period. Any changes to usual treatment will be noted in the study file.

All subjects will be seen again 4 weeks after the final study treatment session and will once again undergo the brief cognitive battery and fMRI scan.

The investigators expect to recruit two subjects at a time for the study and each subject will be enrolled for 5 weeks from the baseline visit.

  Eligibility

Ages Eligible for Study:   50 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects must have a diagnosis of probable or possible Alzheimer's disease, diagnosed using standardized criteria.
  • If subjects are determined by the PI to lack decisional capacity to consent to the study, a legally authorized representative must be available to sign the informed consent on behalf of the subject. In this case the assent of each subject will be obtained as well. If at any time the subject withdraws his or her assent, the subject will be disenrolled from the study.
  • Subjects will score at or below 30 on the 60 item naming section of the Boston Diagnostic Aphasia and/or below 50% on the Controlled Word Association (CFL) Category Naming.

Exclusion Criteria:

  • Subjects newly diagnosed with AD and not yet receiving usual care are not eligible.
  • Subjects must not have pacemakers.
  • They must not have a history of implanted metal objects.
  • They must not have a history of seizures or epilepsy.
  • There must not be any recent history of migraines.
  • There must not be any history of uncontrolled depression.
  • They must not be on any medications that will significantly lower the seizure threshold.
  • Any other medical condition that is judged by the PI to make rTMS unsafe for the subject.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00814697

Locations
United States, New York
The NY Memory Services
New York, New York, United States, 10021
Sponsors and Collaborators
The New York Memory Services
Investigators
Principal Investigator: Gayatri Devi, MD The New York Memory Services
  More Information

Publications:

Responsible Party: Gayatri Devi, MD, Clinical Associate Professor of Neurology & Psychiatry, The New York Memory Services
ClinicalTrials.gov Identifier: NCT00814697     History of Changes
Other Study ID Numbers: 91913-5
Study First Received: December 24, 2008
Results First Received: May 2, 2013
Last Updated: January 8, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by The New York Memory Services:
Alzheimer
Language
Treatment
TMS
rTMS

Additional relevant MeSH terms:
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Dementia
Mental Disorders
Nervous System Diseases
Neurodegenerative Diseases
Tauopathies

ClinicalTrials.gov processed this record on November 25, 2014