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Enhancement of Hippocampal Plasticity Using Repetitive Transcranial Magnetic Stimulation

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: 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

Tracking Information
First Submitted Date  ICMJE January 14, 2019
First Posted Date  ICMJE May 24, 2019
Last Update Posted Date July 14, 2022
Actual Study Start Date  ICMJE October 21, 2020
Estimated Primary Completion Date December 31, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 27, 2021)
  • Brain imaging data [ Time Frame: Baseline ]
    The investigators will acquire MRI images to measure structural and functional connectivity, respectively.
  • 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.
  • Correction rate in memory association recall [ Time Frame: Baseline ]
    Memory tasks will be implemented and measure the correct rate to assess memory function.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 23, 2019)
  • Brain imaging data [ Time Frame: Baseline ]
    The investigators will acquire MRI images to measure structural and functional connectivity, respectively.
  • 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.
  • Correction rate in memory association recall [ Time Frame: Baseline ]
    Memory tasks will be implemented and measure the correct rate to assess memory function.
  • 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.
  • Biometry with Heart Rate Variability [ Time Frame: Baseline ]
    Heart rate variability (HRV) has been used as an indicator of autonomic health or dysfunction.
  • 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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 27, 2021)
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 23, 2019)
  • 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.
  • 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.
  • 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.
  • 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.
Current Other Pre-specified Outcome Measures
 (submitted: October 27, 2021)
  • Brain imaging data [ Time Frame: an average of 1 month ]
    The investigators will acquire MRI images to measure structural and functional connectivity, respectively.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Other Pre-specified Outcome Measures
 (submitted: May 23, 2019)
  • Brain imaging data [ Time Frame: an average of 1 month ]
    The investigators will acquire MRI images to measure structural and functional connectivity, respectively.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
 
Descriptive Information
Brief Title  ICMJE Enhancement of Hippocampal Plasticity Using Repetitive Transcranial Magnetic Stimulation
Official Title  ICMJE Enhancement of Hippocampal Plasticity Using Repetitive Transcranial Magnetic Stimulation
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Mild Cognitive Impairment
Intervention  ICMJE 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)
Study Arms  ICMJE
  • Experimental: Excitatory TBS
    Excitatory TBS
    Intervention: Device: TBS
  • Experimental: Inhibitory TBS
    Inhibitory TBS
    Intervention: Device: TBS
  • Placebo Comparator: Sham TBS
    Sham TBS
    Intervention: Device: TBS
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 23, 2019)		 60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2025
Estimated Primary Completion Date December 31, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
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
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03962959
Other Study ID Numbers  ICMJE 1812171968
R01AG062543 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party University of Arizona
Original Responsible Party Same as current
Current Study Sponsor  ICMJE University of Arizona
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE National Institute on Aging (NIA)
Investigators  ICMJE Not Provided
PRS Account University of Arizona
Verification Date July 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP