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Modulating Cortical Dynamics of Dual-task Standing in MCI

Primary Purpose

Aging, Mild Cognitive Impairment

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
real tACS
sham tACS
Sponsored by
Hebrew SeniorLife
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Aging focused on measuring aging, mild cognitive impairment, non-invasive brain stimulation

Eligibility Criteria

65 Years - 95 Years (Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Healthy older adults: Our target population will be healthy older men and women who are cognitively intact. We will also ensure that participants are not so impaired that they cannot safely participate nor potentially benefit from the intervention. Age 65+ without any cognitive impairment (based in MoCA or TICS) Willing and capable to give informed consent for the participation in the study after it has been thoroughly explained able and willing to comply with all study requirements informed consent form was signed Ability to stand and walk independently Understanding of the informed consent form (ICF) will be assessed by asking the participant to answer the following three questions: 1) What is the purpose of this study? 2) What are the risks of study involvement? 3) If you decide to participate, are you allowed to withdraw from the study at any time? Answers will be recorded by study personnel on the "Assessment of Protocol Understanding" form. Insufficient understanding will be defined by one or more incorrect answers, as determined at the discretion of the investigator. Older MCI participants: Age 65+ Who have been diagnosed with cognitive impairment (based in MoCA or TICS and Clinical Dementia Rating: CDR 0.5) Ability to stand and walk independently Willing and capable to give informed consent for the participation in the study after it has been thoroughly explained Cut off of MOCA score >18 will be applied Able and willing to comply with all study requirements informed consent form was signed Understanding of the ICF will be assessed by asking the participant to answer the following three questions: 1) What is the purpose of this study? 2) What are the risks of study involvement? 3) If you decide to participate, are you allowed to withdraw from the study at any time? Answers will be recorded by study personnel on the "Assessment of Protocol Understanding" form (see attached). Insufficient understanding will be defined by one or more incorrect answers, as determined at the discretion of the investigator. Exclusion Criteria: Healthy older adults: Exclusion Criteria have been selected to ensure safety and optimize compliance while minimizing confounds due to overt disease or conditions that may significantly influence study outcomes. Potentially eligible individuals will complete the Montreal Cognitive Assessment (MoCA) - score < 26 Major psychiatric co-morbidity including major depressive disorder, schizophrenia or psychosis Self-reported diagnosis of Parkinson's disease, Alzheimer's disease or dementia, multiple sclerosis, history of stroke or other neurodegenerative disorder. Self-reported active cancer for which chemo-/radiation therapy is being received. Blindness or other disabilities that prevent task performance Contraindications to tACS, as recorded on a standardized screening questionnaire, which include a reported seizure within the past two years, use of neuroactive drugs, self-reported presence of specific implanted medical devices (e.g., deep brain stimulator, medication infusion pump, cochlear implant, pacemaker, etc.), or the presence of any active dermatological condition, such as eczema, on the scalp Inability to stand or ambulate unassisted for at least 25 feet Hospitalization within the past 3 months due to acute illness or as a result of musculoskeletal injury significantly affecting gait and balance Older MCI participants: Cut off of MOCA score <18 will be applied Major psychiatric co-morbidity including major depressive disorder, schizophrenia or psychosis Blindness or other disabilities that prevent task performance Self-reported history of stroke or neurodegenerative disorders other than MCI. Self-reported active cancer for which chemo-/radiation therapy is being received. Contraindications to tACS, as recorded on a standardized screening questionnaire, which include a reported seizure within the past two years, use of neuro-active drugs, self-reported presence of specific implanted medical devices (e.g., deep brain stimulator, medication infusion pump, cochlear implant, pacemaker, etc.), or the presence of any active dermatological condition, such as eczema, on the scalp.

Sites / Locations

  • Marcus Institute for Aging ResearchRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Sham Comparator

Arm Label

real tACS

sham tACS

Arm Description

The investigators will administer the transcranial alternating current stimulation (tACS) intervention at 10 Hz to the participants. This intervention will utilize 6 electrodes; electrode placement and current parameters for each electrode have been optimized using a standard brain to generate an average electric field of 0.25 V/m. To ensure adherence to current safety recommendations for tACS, optimizations will be constrained to a maximum of total injected current 4.0 mA and a max. current per electrode of 2.0 mA. Stimulation will start and end with a 60 s ramp up/down to maximize comfort. This standard approach is both well-tolerated and safe in older adults. In a separate visit, we will use an active sham in which very low-level currents (0.5 mA total) will be transferred between electrodes in close proximity on the scalp throughout the entire 20-minute session.

The investigators will administer the sham tACS intervention to the participants. They will use an active sham in which very low-level alternating currents (0.5 mA total) will be transferred between electrodes in close proximity on the scalp throughout the entire 20-minute session.

Outcomes

Primary Outcome Measures

EEG alpha-band power
EEG oscillations and frequency coupling at 8-13 Hz
Postural sway speed
This metric assesses the ability to control standing posture

Secondary Outcome Measures

Timed Up and Go Test (TUG)
A common field test of mobility
Postural sway area
This metric assesses the ability to control standing posture
Postural sway path
This metric assesses the ability to control standing posture
EEG theta-band power
EEG oscillations and frequency coupling at 4-7 Hz
EEG beta-band power
EEG oscillations and frequency coupling at 13-30 Hz

Full Information

First Posted
December 19, 2022
Last Updated
March 13, 2023
Sponsor
Hebrew SeniorLife
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1. Study Identification

Unique Protocol Identification Number
NCT05680701
Brief Title
Modulating Cortical Dynamics of Dual-task Standing in MCI
Official Title
Understanding and Modulating Cortical Dynamics of Dual-task Standing in Older Adults With Mild Cognitive Impairment
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 13, 2023 (Actual)
Primary Completion Date
January 2025 (Anticipated)
Study Completion Date
January 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Hebrew SeniorLife

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The investigators have designed a brain stimulation study to understand its effect on an individual's standing, walking, and thinking abilities in older adults with and without mild cognitive impairments (MCI). The transcranial alternating current stimulation (tACS) technology has been safely and effectively used in hundreds of individuals. The purpose of this study is to test whether a single session of tACS as compared to sham intervention, improves standing, walking, and thinking in older adults with and without mild cognitive impairments (MCI). Approximately 60 people will take part in this study.
Detailed Description
Mild Cognitive Impairment (MCI) represents a common prodromal phase of dementia1. As compared to older adults who are cognitively-intact, those with MCI tend to exhibit poor "dual-task" standing balance performance; that is, the ability to maintain balance when standing and simultaneously performing an unrelated cognitive task. Moreover, those older adults who have worse dual-task standing balance are more likely to suffer falls and develop dementia. As such, strategies designed to understand and enhance the brain functionality involved in dual-task standing balance hold great promise to improve daily life function, and potentially, reduce the risk of dementia in this population. Surface electroencephalography (EEG) allows non-invasive assessment of brain activity dynamics over short periods of time, even when standing. It has been demonstrated in younger and older adults that dual-task standing is associated with brain activity fluctuations at specific frequencies. A recent study from our laboratory demonstrated that in older adults, 1) performance of a serial subtraction cognitive task when standing reduces fronto-central alpha power (i.e., fluctuations in the 8-13 Hz band), and 2) those with lower fronto-central alpha power when dual tasking exhibit worse dual task standing balance. Intriguingly, numerous studies have separately linked diminished alpha activity with worse performance on executive function and visuomotor tasks, as well as global cognitive decline in older adults. We therefore contend that therapeutic strategies designed to increase alpha activity hold promise to improve dual-task standing performance, and many other cognitive-motor functions in older adults with and without MCI. To date, however, the effects of enhancing fronto-central alpha activity to improve dual-task balance in older adults with and without MCI have not been studied. Transcranial alternating stimulation (tACS) is a safe, non-invasive brain stimulation technique that utilizes low-amplitude alternating currents to modulate brain activity and entrain specific cortical rhythms depending on the applied stimulation frequency. Targeting alpha band (10 Hz) in the frontal region has been shown to improve cognitive functioning in healthy older adults. However, no studies have investigated the effect of 10 Hz fronto-central stimulation on EEG alpha activity and postural sway outcomes during dual-task standing in older adults with and without MCI. We thus propose to conduct a within-subject cross-over, sham-controlled study in 30 older adults without an overt disease and 30 older adults with MCI. Participants will undergo dual-task standing and cognitive assessments immediately before and after single sessions of 10 Hz tACS (fronto-central alpha stimulation), and active-sham to understand the effect of different stimulation parameters on dual-task standing performance in older adults. We hypothesize that (1) older adults with MCI will demonstrate decreased EEG alpha power during dual-task standing compared to healthy controls, and decreased alpha power will be associated with worse balance outcomes during dual-task standing, and (2) compared to the pre-stimulation condition, participants will exhibit a greater increase in alpha power during the dual-task standing condition following tACS as compared to sham stimulation, and the increase in alpha power from pre-to-post tACS will correlate with a decrease in dual-task postural sway speed from pre-to-post tACS in older adults with and without MCI.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Aging, Mild Cognitive Impairment
Keywords
aging, mild cognitive impairment, non-invasive brain stimulation

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
real tACS
Arm Type
Active Comparator
Arm Description
The investigators will administer the transcranial alternating current stimulation (tACS) intervention at 10 Hz to the participants. This intervention will utilize 6 electrodes; electrode placement and current parameters for each electrode have been optimized using a standard brain to generate an average electric field of 0.25 V/m. To ensure adherence to current safety recommendations for tACS, optimizations will be constrained to a maximum of total injected current 4.0 mA and a max. current per electrode of 2.0 mA. Stimulation will start and end with a 60 s ramp up/down to maximize comfort. This standard approach is both well-tolerated and safe in older adults. In a separate visit, we will use an active sham in which very low-level currents (0.5 mA total) will be transferred between electrodes in close proximity on the scalp throughout the entire 20-minute session.
Arm Title
sham tACS
Arm Type
Sham Comparator
Arm Description
The investigators will administer the sham tACS intervention to the participants. They will use an active sham in which very low-level alternating currents (0.5 mA total) will be transferred between electrodes in close proximity on the scalp throughout the entire 20-minute session.
Intervention Type
Other
Intervention Name(s)
real tACS
Intervention Description
The participant will receive one session of 10 Hz tACS for 20-minutes
Intervention Type
Other
Intervention Name(s)
sham tACS
Intervention Description
The participant will receive one session of active-sham tACS for 20-minutes
Primary Outcome Measure Information:
Title
EEG alpha-band power
Description
EEG oscillations and frequency coupling at 8-13 Hz
Time Frame
Change from immediately before and after each 20-minute session of tACS
Title
Postural sway speed
Description
This metric assesses the ability to control standing posture
Time Frame
Change from immediately before and after each 20-minute session of tACS
Secondary Outcome Measure Information:
Title
Timed Up and Go Test (TUG)
Description
A common field test of mobility
Time Frame
This outcome will be assessed immediately before and after each 20-minute session of tACS
Title
Postural sway area
Description
This metric assesses the ability to control standing posture
Time Frame
This outcome will be assessed immediately before and after each 20-minute session of tACS
Title
Postural sway path
Description
This metric assesses the ability to control standing posture
Time Frame
This outcome will be assessed immediately before and after each 20-minute session of tACS
Title
EEG theta-band power
Description
EEG oscillations and frequency coupling at 4-7 Hz
Time Frame
This outcome will be assessed immediately before and after each 20-minute session of tACS
Title
EEG beta-band power
Description
EEG oscillations and frequency coupling at 13-30 Hz
Time Frame
This outcome will be assessed immediately before and after each 20-minute session of tACS

10. Eligibility

Sex
All
Minimum Age & Unit of Time
65 Years
Maximum Age & Unit of Time
95 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Healthy older adults: Our target population will be healthy older men and women who are cognitively intact. We will also ensure that participants are not so impaired that they cannot safely participate nor potentially benefit from the intervention. Age 65+ without any cognitive impairment (based in MoCA or TICS) Willing and capable to give informed consent for the participation in the study after it has been thoroughly explained able and willing to comply with all study requirements informed consent form was signed Ability to stand and walk independently Understanding of the informed consent form (ICF) will be assessed by asking the participant to answer the following three questions: 1) What is the purpose of this study? 2) What are the risks of study involvement? 3) If you decide to participate, are you allowed to withdraw from the study at any time? Answers will be recorded by study personnel on the "Assessment of Protocol Understanding" form. Insufficient understanding will be defined by one or more incorrect answers, as determined at the discretion of the investigator. Older MCI participants: Age 65+ Who have been diagnosed with cognitive impairment (based in MoCA or TICS and Clinical Dementia Rating: CDR 0.5) Ability to stand and walk independently Willing and capable to give informed consent for the participation in the study after it has been thoroughly explained Cut off of MOCA score >18 will be applied Able and willing to comply with all study requirements informed consent form was signed Understanding of the ICF will be assessed by asking the participant to answer the following three questions: 1) What is the purpose of this study? 2) What are the risks of study involvement? 3) If you decide to participate, are you allowed to withdraw from the study at any time? Answers will be recorded by study personnel on the "Assessment of Protocol Understanding" form (see attached). Insufficient understanding will be defined by one or more incorrect answers, as determined at the discretion of the investigator. Exclusion Criteria: Healthy older adults: Exclusion Criteria have been selected to ensure safety and optimize compliance while minimizing confounds due to overt disease or conditions that may significantly influence study outcomes. Potentially eligible individuals will complete the Montreal Cognitive Assessment (MoCA) - score < 26 Major psychiatric co-morbidity including major depressive disorder, schizophrenia or psychosis Self-reported diagnosis of Parkinson's disease, Alzheimer's disease or dementia, multiple sclerosis, history of stroke or other neurodegenerative disorder. Self-reported active cancer for which chemo-/radiation therapy is being received. Blindness or other disabilities that prevent task performance Contraindications to tACS, as recorded on a standardized screening questionnaire, which include a reported seizure within the past two years, use of neuroactive drugs, self-reported presence of specific implanted medical devices (e.g., deep brain stimulator, medication infusion pump, cochlear implant, pacemaker, etc.), or the presence of any active dermatological condition, such as eczema, on the scalp Inability to stand or ambulate unassisted for at least 25 feet Hospitalization within the past 3 months due to acute illness or as a result of musculoskeletal injury significantly affecting gait and balance Older MCI participants: Cut off of MOCA score <18 will be applied Major psychiatric co-morbidity including major depressive disorder, schizophrenia or psychosis Blindness or other disabilities that prevent task performance Self-reported history of stroke or neurodegenerative disorders other than MCI. Self-reported active cancer for which chemo-/radiation therapy is being received. Contraindications to tACS, as recorded on a standardized screening questionnaire, which include a reported seizure within the past two years, use of neuro-active drugs, self-reported presence of specific implanted medical devices (e.g., deep brain stimulator, medication infusion pump, cochlear implant, pacemaker, etc.), or the presence of any active dermatological condition, such as eczema, on the scalp.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nicole LaGanke
Phone
617-971-5358
Email
nicolelaganke@hsl.harvard.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Kathy Tasker
Phone
6179715351
Email
kathytasker@hsl.harvard.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Melike Kahya
Organizational Affiliation
Marcus Institute for Aging Research
Official's Role
Principal Investigator
Facility Information:
Facility Name
Marcus Institute for Aging Research
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02131
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nicole LaGanke
Phone
617-971-5358
Email
nicolelaganke@hsl.harvard.edu

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
The HSL Marcus Institute for Aging Research will promote the development of new research and new investigators by making the data available to outside investigators. The database will include demographic, clinical, functional, and neurophysiologic data from all participants. All data will be stripped of primary identifiers and entered into a master database. All data collection procedures, variable definitions and codes, field locations, and frequencies will be documented in a separate file.
IPD Sharing Time Frame
The investigators will make the data and associated documentation available once summary data are published or otherwise made available, starting six months after publication.
IPD Sharing Access Criteria
The investigators will make the data and associated documentation available to users only under a data-sharing agreement that provides for: 1) a commitment to using data only for research purposes and not to identify any particular participant; 2) a commitment to securing the data using appropriate computer technology; and 3) a commitment to destroying or returning the data after analyses are completed. The availability of data will be advertised over the Internet through websites maintained by Hebrew SeniorLife and Harvard Medical School. All investigators wishing to access the data will submit a brief proposal describing their research project, data needs, regulatory approvals, and mechanisms to assure patient confidentiality. Upon affirmative review by the Principal Investigator and co-investigators of this study, a data-sharing agreement will be signed and the requesting investigators will be given a working data file and appropriate documentation.

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Modulating Cortical Dynamics of Dual-task Standing in MCI

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