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Enhancement of Hippocampal Plasticity Using Repetitive Transcranial Magnetic Stimulation

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ClinicalTrials.gov Identifier: NCT03962959
Recruitment Status : Recruiting
First Posted : May 24, 2019
Last Update Posted : July 14, 2022
Sponsor:
Collaborator:
National Institute on Aging (NIA)
Information provided by (Responsible Party):
University of Arizona

Study Description
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Brief Summary:

The ultimate goal of this study is to develop non-invasive, painless repetitive transcranial magnetic stimulation (rTMS) protocols to prevent cognitive decline in patients with mild cognitive impairment (MCI) and cognitively normal individuals at high risk of developing Alzheimer's disease (AD). Currently, 1 in 9 adults over the age of 65 have AD, which currently totals more than 5 million Americans and this number is expected to rise as high as 16 million by 2050.

MCI is a clinical syndrome that represents the gray area between healthy aging and dementia. Those with amnestic MCI (aMCI) have memory problems more severe than normal for their age and education, but their symptoms are not as severe as those of people with AD. Patients with aMCI are at high risk for AD. Notably, roughly half of those with MCI will continue to progress and convert to clinical dementia within 3 years. Alternatively, it is also worthwhile to study cognitively healthy older adults who carry genes that may increase the risk of AD. The frequency of the human APOE gene ε4 allele increases in patients with AD and the ε4 allele is also associated with an earlier age of disease onset.

Currently, there are no known therapies that can effectively modify the progression and hallmark symptoms of AD. Therefore, it is crucial to provide an early intervention in patients with aMCI to delay or prevent the progression to AD.

More specifically, this project has two specific aims:

  1. To plan personalized non-invasive brain stimulation location by brain Imaging with Magnetic Resonance Imaging (MRI) in Mild Cognitive Impairment (MCI)
  2. To identify potential personalized cognitive enhancement strategy (such as dosage or patterns) of Transcranial Magnetic Stimulation (TMS) in MCI.

Techniques to artificially and precisely stimulate brain tissue are increasingly recognized as valuable tools both in clinical practice and in cognitive neuroscience studies among healthy individuals and people with clinical conditions. With these practices, researchers can safely stimulate specific regions of the brain to explore causal relationships that comprise the brain's circuitry and modulate behavior.


Condition or disease Intervention/treatment Phase
Mild Cognitive Impairment Device: TBS Not Applicable

Detailed Description:

In total, 60 participants (50-80 years old) with MCI will be recruited to participate in this trial.

Participants will be asked to receive 30 intervention sessions for three different protocols (10 sessions for each). Before and after the interventions, MRI and Cognitive tasks will be utilized again as the outcome measurements. There is a one-month interval between each protocol. Each intervention will be around half hour to an hour and each outcome measurement will take another two hours.

Each block includes:

  • MRI+ Memory pre-assessment (2 hours/session)
  • TMS * 10 (10 sessions; 0.5 hours/session)
  • MRI+ Memory post-assessment (2 hours/session) Participants will experience each of the three TMS protocols. The total time commitment across these sessions will be approximately 27 hours.

There will be another 2 testing sessions to evaluate intervention effects. They will be scheduled at the beginning, and 1 month after the end of the intervention sessions. All sessions will take place in the Biosciences Research Laboratories (BSLR) Building (1230 N. Cherry Ave., Tucson, AZ 85721). The schematic below outlines the components of the sessions.

The investigators will acquire the following data during components for primary outcome measures and secondary measures.

1) Brain imaging data 2) Neuropsychological data and demographic data 3) Cognitive tasks 4) Biological sample

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Enhancement of Hippocampal Plasticity Using Repetitive Transcranial Magnetic Stimulation
Actual Study Start Date : October 21, 2020
Estimated Primary Completion Date : December 31, 2024
Estimated Study Completion Date : June 30, 2025
Arms and Interventions
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Arm Intervention/treatment
Experimental: Excitatory TBS
Excitatory TBS
 Device: TBS
TMS is a non-invasive brain stimulation technique. The primary aim of the study will be to verify the deliverability of the TMS effect on the hippocampus and determine which stimulation protocol is more beneficial to each participant.
Other Name: Theta Burst Stimulation (TBS)
Experimental: Inhibitory TBS
Inhibitory TBS
 Device: TBS
TMS is a non-invasive brain stimulation technique. The primary aim of the study will be to verify the deliverability of the TMS effect on the hippocampus and determine which stimulation protocol is more beneficial to each participant.
Other Name: Theta Burst Stimulation (TBS)
Placebo Comparator: Sham TBS
Sham TBS
 Device: TBS
TMS is a non-invasive brain stimulation technique. The primary aim of the study will be to verify the deliverability of the TMS effect on the hippocampus and determine which stimulation protocol is more beneficial to each participant.
Other Name: Theta Burst Stimulation (TBS)


Outcome Measures
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Primary Outcome Measures :
  1. Brain imaging data [ Time Frame: Baseline ]
    The investigators will acquire MRI images to measure structural and functional connectivity, respectively.

  2. NACC Neuropsychological batteries [ Time Frame: Baseline ]
    The investigators will use Neuropsychological batteries, which would calculate the Z-score, for measuring cognitions. With Z-score, the investigators can classify participants into MCI or non-MCI group.

  3. Correction rate in memory association recall [ Time Frame: Baseline ]
    Memory tasks will be implemented and measure the correct rate to assess memory function.

  4. Specimen sample [ Time Frame: 1 day (Only once in the beginning phase) ]
    A specimen for DNA will be collected and determine whether participants have APOE genotype.


Secondary Outcome Measures :
  1. Brain imaging data [ Time Frame: 2 weeks after the intervention phase begin ]
    The investigators will acquire MRI images to measure structural and functional connectivity, respectively.

  2. Correction rate in memory association recall [ Time Frame: 2 weeks after the intervention phase begin ]
    Memory tasks will be implemented and measure the correct rate to assess memory function.


Other Outcome Measures:
  1. Brain imaging data [ Time Frame: an average of 1 month ]
    The investigators will acquire MRI images to measure structural and functional connectivity, respectively.

  2. Brain imaging data [ Time Frame: 3 months after the intervention phase complete ]
    The investigators will acquire MRI images to measure structural and functional connectivity, respectively.

  3. NACC Neuropsychological batteries [ Time Frame: an average of 1 month ]
    The investigators will use Neuropsychological batteries, which would calculate the Z-score, for measuring cognitions function. With Z-score, the investigators can classify participants into MCI or non-MCI group.

  4. NACC Neuropsychological batteries [ Time Frame: 3 months after the intervention phase complete ]
    The investigators will use Neuropsychological batteries, which would calculate the Z-score, for measuring cognitions. With Z-score, the investigators can classify participants into MCI or non-MCI group.

  5. Correction rate in memory association recall [ Time Frame: an average of 1 month ]
    Memory tasks will be implemented and measure the correct rate to assess memory function.

  6. Correction rate in memory association recall [ Time Frame: 3 months after the intervention phase complete ]
    Memory tasks will be implemented and measure the correct rate to assess memory function.


Eligibility Criteria
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Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   50 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Individuals with mild cognitive impairment (MCI Group)

Inclusion Criteria:

  • Age 50-80 years
  • MCI clinical criteria: (a) self- or informant-reported cognitive complaint; (b) preserved independence in functional abilities; and (c) absence of dementia.
  • Objective cognitive impairment supported by the following measures of general cognitive function: (a) Mini-Mental State Exam (MMSE) 24-27 (inclusive); (b) Montreal Cognitive Assessment (MoCA) 18-26 (inclusive); or (c) Clinical Dementia Rating Scale score of 0.5.
  • Right handed
  • English speaking
  • Able to attend daily intervention (Monday-Friday) for 4 weeks
  • Not enrolled in another interventional study within 6 months prior to beginning this study

Exclusion Criteria:

  • Contraindications to transcranial magnetic stimulation (TMS) or magnetic resonance imaging (MRI)
  • Other neurological disorders (e.g. stroke, head injuries, or multiple sclerosis)
  • Untreated depression
  • Current cancer treatment or other medical problems that might independently affect cognitive function
  • Clinical Dementia Rating Scale score more than 1.0
Contacts and Locations
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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): NCT03962959


Contacts
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Contact: Yu-Chin Chen, M.D. 520-626-7755 tms-lab@list.arizona.edu
Contact: Ying-hui Chou, Sc.D. 520-626-7755 tms-lab@list.arizona.edu

Locations
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United States, Arizona
Bioscience Research Laboratory Recruiting
Tucson, Arizona, United States, 85719
Contact: Lisbeth Haaheim       tms-lab@list.arizona.edu   
Sponsors and Collaborators
University of Arizona
National Institute on Aging (NIA)
More Information
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Responsible Party: University of Arizona
ClinicalTrials.gov Identifier: NCT03962959    
Other Study ID Numbers: 1812171968
R01AG062543 ( U.S. NIH Grant/Contract )
First Posted: May 24, 2019    Key Record Dates
Last Update Posted: July 14, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Keywords provided by University of Arizona:
Mild Cognitive Impairment
Transcranial Magnetic Stimulation
Additional relevant MeSH terms:
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Cognitive Dysfunction
Cognition Disorders
Neurocognitive Disorders
Mental Disorders