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Network Modulation in Alzheimer's Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04045990
Recruitment Status : Recruiting
First Posted : August 6, 2019
Last Update Posted : August 6, 2019
Sponsor:
Information provided by (Responsible Party):
Mark Eldaief, MD, Massachusetts General Hospital

Brief Summary:

The purpose of this study is to assess the effects of non-invasive brain stimulation on memory and language ability in patients with two phenotypic variations of underlying Alzheimer disease pathology: amnestic mild cognitive impairment (aMCI) and logopenic variant of primary progressive aphasia (lvPPA). This study will use repetitive Transcranial Magnetic Stimulation (rTMS) to stimulate nodes of networks that are thought to be affected in these two conditions. Specifically, a node of the Default Mode Network (DMN)-the angular gyrus (AG)-will be stimulated in aMCI patients; and a node of the language network-the posterior inferior frontal gyrus (pIFG) will be stimulated in patients with lvPPA.

We will use functional connectivity MRI (fcMRI) to assess changes in functional network architecture following the stimulation. We will also assess putative cognitive improvements resulting from the stimulation by in-depth language testing in lvPPA patients and in-depth memory testing in aMCI patients.


Condition or disease Intervention/treatment Phase
Alzheimer Disease Primary Progressive Aphasia Mild Cognitive Impairment Device: repetitive transcranial magnetic stimulation (rTMS) Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Crossover Assignment
Intervention Model Description: Patients with each condition will each undergo, in a crossover, within-subject design, two clocks of rTMS: active and SHAM.The order of active and SHAM blocks will be counterbalanced across subjects.
Masking: Single (Participant)
Masking Description: All participants will undergo SHAM stimulation as a control condition. They will be blinded as to whether they are receiving active or SHAM stimulation.
Primary Purpose: Treatment
Official Title: Neuromodulation of Language and Memory Networks in Alzheimer's Disease
Actual Study Start Date : September 1, 2018
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2021


Arm Intervention/treatment
Experimental: Active stimulation
Active rTMS will be administered with a MagPro X100 stimulator (MagVenture, Denmark), using a 70 mm figure-of-eight liquid cooled coil capable of doing active or sham stimulation (e.g. the Cool B70 coil or the Cool B65 A/P coil). Active rTMS will be delivered at 80-120% of a patient's resting or active motor threshold. rTMS will be administered in an excitatory pattern as 20Hz. Stimulation parameters will remain well within established safety guidelines (Rossi et al. 2009).
Device: repetitive transcranial magnetic stimulation (rTMS)
rTMS is a method to focally and reversibly stimulate a pre-specified cortical target. rTMS works through the principle of electromagnetic induction.

Sham Comparator: SHAM stimulation
SHAM stimulation will also be administered with a MagPro X100 stimulator (MagVenture, Denmark), using a 70 mm figure-of-eight liquid cooled coil capable of doing active or sham stimulation (e.g. the Cool B70 coil or the Cool B65 A/P coil). SHAM rTMS will be delivered at 80-120% of a patient's resting or active motor threshold. SHAM stimulation will be delivered to the exact same cortical targets as active rTMS. While no electromagnetic stimulation will be delivered during SHAM, the sounds will approximate active stimulation and skin electrodes will approximate the sensation of active rTMS. Inclusion of a sham condition in this protocol is critical to measure whether or not the stimulation is improving memory or language performance, or whether practice effects or other non-specific effects are responsible for any changes in memory or language performance which may be observed.
Device: repetitive transcranial magnetic stimulation (rTMS)
rTMS is a method to focally and reversibly stimulate a pre-specified cortical target. rTMS works through the principle of electromagnetic induction.




Primary Outcome Measures :
  1. Boston Naming Test [ Time Frame: Up to 5 weeks ]
    A test of confrontation naming of drawn pictures.

  2. Western Aphasia Battery-repetition [ Time Frame: Up to 5 weeks ]
    A test of the ability to repeat phonetically complex phrases

  3. Western Aphasia Battery-reading comprehension [ Time Frame: Up to 5 weeks ]
    A test of the ability to correctly comprehend read material

  4. Western Aphasia Battery-spelling [ Time Frame: Up to 5 weeks ]
    A test of the ability to spell irregular words.

  5. Controlled Oral Word Association Test [ Time Frame: Up to 5 weeks ]
    A test of word generation, e.g. generation of as many words as possible beginning with a certain letter of the alphabet.

  6. Cambridge Semantic Battery [ Time Frame: Up to 5 weeks ]
    A test of semantic knowledge through word-pairings.

  7. The Northwestern Anagram Test [ Time Frame: Up to 5 weeks ]
    A test of non-verbal production of sentences.

  8. Picture Description Test [ Time Frame: Up to 5 weeks ]
    A test in which patients write a paragraph describing a picture, such as a picnic or the cookie theft picture.

  9. Changes in intrinsic functional connectivity [ Time Frame: Up to 5 weeks ]
    Changes in region-to-region functional connectivity within the stimulated networks will be assessed, e.g. changes in connectivity in the DMN will be assessed in aMCI patients and changes in the language network will be assessed in lvPPA patients.



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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients, age 18-90, who carry a diagnosis of either the logopenic variant (lvPPA) of PPA or amnestic MCI (aMCI). Patients must have been observed for at least one year by a specialized clinician.
  2. The presence of underlying AD pathology must be verified by a prior amyloid-PET and/or Tau-PET imaging (done as part of a prior protocol), or CSF biomarkers of AD pathology.
  3. Patients with lvPPA must have at least mild to moderate language impairment.
  4. Patients with aMCI must meet criteria for this condition, including the presence of at least mild to moderate episodic memory impairment.
  5. Patients must be native English speakers.
  6. Patients must have a study partner (e.g. spouse, sibling, adult child, friend) who can accompany them to all study visits.

Exclusion Criteria:

  1. Any history of seizures, unexplained loss of consciousness or a first-degree family member with epilepsy (to ensure safety to receive rTMS).
  2. Any history of significant co-occurring neurological illness unrelated to the neurodegenerative disease in question (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 DSM criteria.
  4. MRI evidence of significant (e.g. confluent leukoariosis or stroke) cerebrovascular disease, hydrocephalus or the presence of a space-occupying intra-cranial mass.
  5. Contraindications to MRI or rTMS including: cardiac pacemaker or pacemaker wires, neurostimulators, implanted pumps, metal in the body (rods, plates, screws, shrapnel, dentures, IUD), surgical aneurysm clips in the head, previous neurosurgery or cochlear implants.
  6. In line with published MGH IRB guidelines for rTMS, pregnancy must be ruled out by urine ß-HCG 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04045990


Contacts
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Contact: Mark C Eldaief, M.D. (617) 726-1728 mark.eldaief@mgh.harvard.edu

Locations
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United States, Massachusetts
Massachusetts General Hospital Recruiting
Charlestown, Massachusetts, United States, 02129
Contact: Courtney Sullivan    617-643-5568    csullivan65@partners.org   
Sponsors and Collaborators
Brigham and Women's Hospital
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Responsible Party: Mark Eldaief, MD, Assistant Professor of Neurology, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT04045990    
Other Study ID Numbers: 2018P001362
First Posted: August 6, 2019    Key Record Dates
Last Update Posted: August 6, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: There is no plan to share IPD with researchers outside of this protocol.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Alzheimer Disease
Aphasia
Aphasia, Primary Progressive
Pick Disease of the Brain
Frontotemporal Dementia
Cognitive Dysfunction
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Cognition Disorders
Speech Disorders
Language Disorders
Communication Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Frontotemporal Lobar Degeneration
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases