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MRI Guided Hippocampal Stimulation With Transcranial Magnetic Stimulation

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ClinicalTrials.gov Identifier: NCT03962959
Recruitment Status : Recruiting
First Posted : May 24, 2019
Last Update Posted : May 24, 2019
Sponsor:
Information provided by (Responsible Party):
University of Arizona

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) and healthy older adults.
  2. To identify potential personalized cognitive enhancement strategy (such as dosage or patterns) of Transcranial Magnetic Stimulation (TMS) in MCI and healthy older adults.

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: TMS -low-dose iTBS Device: TMS -medium-dose iTBS Device: TMS -high-dose iTBS Device: TMS -low-dose cTBS Device: TMS -medium-dose cTBS Device: TMS -high-dose cTBS Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: MRI Guided Hippocampal Stimulation With Transcranial Magnetic Stimulation
Actual Study Start Date : April 18, 2019
Estimated Primary Completion Date : April 1, 2023
Estimated Study Completion Date : April 1, 2024

Arm Intervention/treatment
Active Comparator: Healthy Controls

Healthy Controls: Participants who are matched for age and gender. This group will undergo Transcranial Magnetic Stimulation (TMS) protocol.

Intervention: Device:

TMS -low-dose iTBS, TMS -medium-dose iTBS, TMS -high-dose iTBS, TMS -low-dose cTBS, TMS -medium-dose cTBS, TMS -high-dose cTBS

Device: TMS -low-dose iTBS
TMS in a non-invasive brain stimulation technique. The primary aim of the study will be to verify the deliverability of the TMS effect to the hippocampus and determine which stimulation protocol is more beneficial to each participant. The "dose" corresponds to number of stimuli per TBS session: low-dose corresponds with 600 stimuli. The iTBS paradigm is also involved the application of 3 pulses of 50 Hz applied at 5 Hz.
Other Name: Theta Burst Stimulation (TBS)

Device: TMS -medium-dose iTBS
TMS in a non-invasive brain stimulation technique. The primary aim of the study will be to verify the deliverability of the TMS effect to the hippocampus and determine which stimulation protocol is more beneficial to each participant. The "dose" corresponds to number of stimuli per TBS session: medium-dose corresponds with 1200 stimuli. The iTBS paradigm is also involved the application of 3 pulses of 50 Hz applied at 5 Hz.
Other Name: Theta Burst Stimulation (TBS)

Device: TMS -high-dose iTBS
TMS in a non-invasive brain stimulation technique. The primary aim of the study will be to verify the deliverability of the TMS effect to the hippocampus and determine which stimulation protocol is more beneficial to each participant. The "dose" corresponds to number of stimuli per TBS session: high-dose corresponds with 1800 stimuli. The iTBS paradigm is also involved the application of 3 pulses of 50 Hz applied at 5 Hz.
Other Name: Theta Burst Stimulation (TBS)

Device: TMS -low-dose cTBS
TMS in a non-invasive brain stimulation technique. The primary aim of the study will be to verify the deliverability of the TMS effect to the hippocampus and determine which stimulation protocol is more beneficial to each participant. The "dose" corresponds to number of stimuli per TBS session: low-dose corresponds with 600 stimuli. The cTBS paradigm consists of 3 pulses of 50 Hz stimulation repeated at 200-ms interval (i.e., 5 Hz) for 40 seconds (600 stimuli in total).
Other Name: Theta Burst Stimulation (TBS)

Device: TMS -medium-dose cTBS
TMS in a non-invasive brain stimulation technique. The primary aim of the study will be to verify the deliverability of the TMS effect to the hippocampus and determine which stimulation protocol is more beneficial to each participant. The "dose" corresponds to number of stimuli per TBS session: medium-dose corresponds with 1200 stimuli. The cTBS paradigm consists of 3 pulses of 50 Hz stimulation repeated at 200-ms interval (i.e., 5 Hz) for 40 seconds (600 stimuli in total).
Other Name: Theta Burst Stimulation (TBS)

Device: TMS -high-dose cTBS
TMS in a non-invasive brain stimulation technique. The primary aim of the study will be to verify the deliverability of the TMS effect to the hippocampus and determine which stimulation protocol is more beneficial to each participant. The "dose" corresponds to number of stimuli per TBS session: high-dose corresponds with 1800 stimuli. The cTBS paradigm consists of 3 pulses of 50 Hz stimulation repeated at 200-ms interval (i.e., 5 Hz) for 40 seconds (600 stimuli in total).
Other Name: Theta Burst Stimulation (TBS)

Experimental: Mild Cognitive Impairment
  • Mild Cognitive Impairment (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. Intervention: Device: TMS -low-dose iTBS, TMS -medium-dose iTBS, TMS -high-dose iTBS, TMS -low-dose cTBS, TMS -medium-dose cTBS, TMS -high-dose cTBS
Device: TMS -low-dose iTBS
TMS in a non-invasive brain stimulation technique. The primary aim of the study will be to verify the deliverability of the TMS effect to the hippocampus and determine which stimulation protocol is more beneficial to each participant. The "dose" corresponds to number of stimuli per TBS session: low-dose corresponds with 600 stimuli. The iTBS paradigm is also involved the application of 3 pulses of 50 Hz applied at 5 Hz.
Other Name: Theta Burst Stimulation (TBS)

Device: TMS -medium-dose iTBS
TMS in a non-invasive brain stimulation technique. The primary aim of the study will be to verify the deliverability of the TMS effect to the hippocampus and determine which stimulation protocol is more beneficial to each participant. The "dose" corresponds to number of stimuli per TBS session: medium-dose corresponds with 1200 stimuli. The iTBS paradigm is also involved the application of 3 pulses of 50 Hz applied at 5 Hz.
Other Name: Theta Burst Stimulation (TBS)

Device: TMS -high-dose iTBS
TMS in a non-invasive brain stimulation technique. The primary aim of the study will be to verify the deliverability of the TMS effect to the hippocampus and determine which stimulation protocol is more beneficial to each participant. The "dose" corresponds to number of stimuli per TBS session: high-dose corresponds with 1800 stimuli. The iTBS paradigm is also involved the application of 3 pulses of 50 Hz applied at 5 Hz.
Other Name: Theta Burst Stimulation (TBS)

Device: TMS -low-dose cTBS
TMS in a non-invasive brain stimulation technique. The primary aim of the study will be to verify the deliverability of the TMS effect to the hippocampus and determine which stimulation protocol is more beneficial to each participant. The "dose" corresponds to number of stimuli per TBS session: low-dose corresponds with 600 stimuli. The cTBS paradigm consists of 3 pulses of 50 Hz stimulation repeated at 200-ms interval (i.e., 5 Hz) for 40 seconds (600 stimuli in total).
Other Name: Theta Burst Stimulation (TBS)

Device: TMS -medium-dose cTBS
TMS in a non-invasive brain stimulation technique. The primary aim of the study will be to verify the deliverability of the TMS effect to the hippocampus and determine which stimulation protocol is more beneficial to each participant. The "dose" corresponds to number of stimuli per TBS session: medium-dose corresponds with 1200 stimuli. The cTBS paradigm consists of 3 pulses of 50 Hz stimulation repeated at 200-ms interval (i.e., 5 Hz) for 40 seconds (600 stimuli in total).
Other Name: Theta Burst Stimulation (TBS)

Device: TMS -high-dose cTBS
TMS in a non-invasive brain stimulation technique. The primary aim of the study will be to verify the deliverability of the TMS effect to the hippocampus and determine which stimulation protocol is more beneficial to each participant. The "dose" corresponds to number of stimuli per TBS session: high-dose corresponds with 1800 stimuli. The cTBS paradigm consists of 3 pulses of 50 Hz stimulation repeated at 200-ms interval (i.e., 5 Hz) for 40 seconds (600 stimuli in total).
Other Name: Theta Burst Stimulation (TBS)




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

  5. Biometry with Heart Rate Variability [ Time Frame: Baseline ]
    Heart rate variability (HRV) has been used as an indicator of autonomic health or dysfunction.

  6. Frailty assessment [ Time Frame: Baseline ]
    Frailty will be assessed by measuring motion of forearm and upper-arm via wearable motion sensors attached to the upper extremity.


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.

  3. Biometry with Heart Rate Variability [ Time Frame: 2 weeks after the intervention phase begin ]
    Heart rate variability (HRV) has been used as an indicator of autonomic health or dysfunction.

  4. Frailty assessment [ Time Frame: 2 weeks after the intervention phase begin ]
    Frailty will be assessed by measuring motion of forearm and upper-arm via wearable motion sensors attached to the upper extremity.


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.

  7. Biometry with Heart Rate Variability [ Time Frame: an average of 1 month ]
    Heart rate variability (HRV) has been used as an indicator of autonomic health or dysfunction.

  8. Biometry with Heart Rate Variability [ Time Frame: 3 months after the intervention phase complete ]
    Heart rate variability (HRV) has been used as an indicator of autonomic health or dysfunction.

  9. Frailty assessment [ Time Frame: an average of 1 month ]
    Frailty will be assessed by measuring motion of forearm and upper-arm via wearable motion sensors attached to the upper extremity.

  10. Frailty assessment [ Time Frame: 3 months after the intervention phase complete ]
    Frailty will be assessed by measuring motion of forearm and upper-arm via wearable motion sensors attached to the upper extremity.



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:   Yes
Criteria
  1. 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
  2. Cognitively normal adults (CN group)

Inclusion Criteria:

  • Age 50-80 years
  • No cognitive impairment supported by the following measures of general cognitive function: (a) Mini-Mental State Exam (MMSE) > 27; (b) Montreal Cognitive Assessment (MoCA) > 26; and (c) Clinical Dementia Rating Scale score of 0.
  • Right handed
  • English speaking
  • Able to attend daily session (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

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. (310) 279-0951 yuchinchen@email.arizona.edu
Contact: Ying-hui Chou, Sc.D. (520) 626-3133 yinghuichou@email.arizona.edu

Locations
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United States, Arizona
Bioscience Research Laboratory Recruiting
Tucson, Arizona, United States, 85719
Contact: Robert Sandoval    520-626-8512    rsandova@bio5.org   
Sponsors and Collaborators
University of Arizona

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Responsible Party: University of Arizona
ClinicalTrials.gov Identifier: NCT03962959     History of Changes
Other Study ID Numbers: 1812171968
First Posted: May 24, 2019    Key Record Dates
Last Update Posted: May 24, 2019
Last Verified: January 2019
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
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No

Keywords provided by University of Arizona:
Mild Cogitive Impairment
Transcranial Magnetic Stimulation

Additional relevant MeSH terms:
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Cognitive Dysfunction
Cognition Disorders
Neurocognitive Disorders
Mental Disorders