Enhancement of Hippocampal Plasticity Using Repetitive Transcranial Magnetic Stimulation

Mild Cognitive Impairment Clinical Trial

Official title:

Enhancement of Hippocampal Plasticity Using Repetitive Transcranial Magnetic Stimulation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03962959
• Other study ID #: 1812171968
• Secondary ID: R01AG062543
• Status: Recruiting
• Phase: N/A
• Start date: October 21, 2020
• Est. completion date: June 30, 2025

Study information

• Verified date: December 2023
• Source: University of Arizona
• Contact: Yu-Chin Chen, M.D.
• Phone: 520-626-7755
• Email: tms-lab[@]list.arizona.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: June 30, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Mild Cognitive Impairment

Intervention

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.

Locations

Country	Name	City	State
United States	Bioscience Research Laboratory	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
University of Arizona	National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Brain imaging data	The investigators will acquire MRI images to measure structural and functional connectivity, respectively.	an average of 1 month
Other	Brain imaging data	The investigators will acquire MRI images to measure structural and functional connectivity, respectively.	3 months after the intervention phase complete
Other	NACC Neuropsychological batteries	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.	an average of 1 month
Other	NACC Neuropsychological batteries	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 months after the intervention phase complete
Other	Correction rate in memory association recall	Memory tasks will be implemented and measure the correct rate to assess memory function.	an average of 1 month
Other	Correction rate in memory association recall	Memory tasks will be implemented and measure the correct rate to assess memory function.	3 months after the intervention phase complete
Primary	Brain imaging data	The investigators will acquire MRI images to measure structural and functional connectivity, respectively.	Baseline
Primary	NACC Neuropsychological batteries	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.	Baseline
Primary	Correction rate in memory association recall	Memory tasks will be implemented and measure the correct rate to assess memory function.	Baseline
Primary	Specimen sample	A specimen for DNA will be collected and determine whether participants have APOE genotype.	1 day (Only once in the beginning phase)
Secondary	Brain imaging data	The investigators will acquire MRI images to measure structural and functional connectivity, respectively.	2 weeks after the intervention phase begin
Secondary	Correction rate in memory association recall	Memory tasks will be implemented and measure the correct rate to assess memory function.	2 weeks after the intervention phase begin