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Individualized Brain Stimulation to Improve Mobility in Alzheimer's Disease (ISTIM-AD)

Primary Purpose

Alzheimer Dementia, Presenile Alzheimer Dementia, Aging

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Personalized tDCS
Active-Sham
Sponsored by
Hebrew SeniorLife
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer Dementia focused on measuring Aging

Eligibility Criteria

65 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Men and women aged 65 and older living within supportive housing facilities
  • Mild Alzheimer's disease (AD) defined by the combination of 1) at least mild cognitive impairment defined as a modified TICS score of ≤ 34, 2) informant-report of Instrumental Activities of Daily Living impairment as defined as a score of ≥ 6 on the NACC Functional Activities Questionnaire, and 3) a Clinical Dementia Rating score of 1.

Exclusion Criteria:

  • Inability to secure informant participation
  • Unwillingness to cooperate or participate in the study protocol
  • An inability to ambulate without the assistance of another person (canes or walkers allowed)
  • A clinical history of stroke, Parkinson's disease or parkinsonian symptoms, multiple sclerosis, normal pressure hydrocephalus, or other neurological conditions outside of mild AD.
  • Any report of severe lower-extremity arthritis or physician-diagnosis of peripheral neuropathy
  • Use of antipsychotics, anti-seizure, benzodiazepines, or other neuroactive medications
  • Severe depression defined by a Center for Epidemiologic Studies Depression scale score greater than 16
  • Any report of physician-diagnosis of schizophrenia, bipolar disorder, or other psychiatric illness
  • Contraindications to MRI or tDCS, including reported seizure within the past two years, use of neuropsychological-active drugs, the risk of metal objects anywhere in the body, self-reported presence of specific implanted medical devices (e.g., deep brain stimulator, medication infusion pump, cochlear implant, pacemakers, etc.), or the presence of any active dermatological condition, such as eczema, on the scalp

Sites / Locations

  • Hebrew Rehabilitation CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Personalized tDCS

Active-Sham

Arm Description

Baseline MRIs will enable personalization of tDCS via current flow modeling for optimization to each participant with the goal of generating an average electric field of 0.25 V/m within their identified left dlPFC. The direct current delivered by any one electrode will not exceed 2.0 mA and the total amount of current from all electrodes will not exceed 4 mA. Each 20-minutes session will begin and end with a 60-second ramp up/down of current amplitude to maximize comfort.

The investigators 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. This intervention will be optimized to each participant to deliver currents designed to not significantly influence their cortical tissue, but still mimic the cutaneous sensations induced by tDCS.

Outcomes

Primary Outcome Measures

Recruitment efficiency
The number of residents that need to be screened in order to enroll one participant into the trial.
Retention
The percentage of enrolled participants who complete the trial.
Blinding
A blinding efficacy questionnaire will be used to record participant guesses of their assigned intervention (real or placebo), as well as the confidence of these guesses on a scale from 1=Not confident to 10=Extremely confident.
Montreal Cognitive Assessment (MoCA) total score
This common test assesses global cognitive function. Maximum score on the MoCA is 30 points (minimum = 0), with higher scores associated with better outcomes.
Dual task gait speed
This metric assesses the ability to control gait while performing a secondary cognitive task.
Dual task standing postural sway area
This metric assesses the ability to control standing posture while performing a secondary cognitive task.

Secondary Outcome Measures

Trail making test A-B
This metric assesses cognitive executive function.
Digit Span
This common test assesses working memory.
Digit Symbol Substitution Test
This common test assesses sustained attention and motor speed.
Category and Phonemic Fluency Test
This common test assesses word retrieval.
Hopkins Verbal Learning Test
This common test assesses memory.
Dual task stride time variability
This metric assesses the ability to control gait while performing a secondary cognitive task.
Dual task standing postural sway speed
This metric assesses the ability to control standing posture while performing a secondary cognitive task.
Timed Up-and-Go
This metric assesses mobility.
Five-day accelerometry-based physical activity
This metric assesses the quantity and quality of habitual physical activity.
Centers for Epidemiologic Studies Depression Scale
This metric assesses mood.

Full Information

First Posted
February 13, 2020
Last Updated
December 15, 2022
Sponsor
Hebrew SeniorLife
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1. Study Identification

Unique Protocol Identification Number
NCT04289402
Brief Title
Individualized Brain Stimulation to Improve Mobility in Alzheimer's Disease
Acronym
ISTIM-AD
Official Title
Modulating Brain Activity to Improve Cognitive-motor Function in Alzheimer's Disease
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 31, 2020 (Actual)
Primary Completion Date
May 31, 2024 (Anticipated)
Study Completion Date
June 30, 2024 (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
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
The objective of this study is to conduct a pilot, randomized sham-controlled trials to determine the feasibility and effects of a 10-session personalized tDCS intervention targeting the left dorsolateral prefrontal cortex on cognitive function, dual task standing and walking, and other metrics of mobility in 24 older adults with mild AD living in supportive housing.
Detailed Description
Beyond the profound impact on memory, Alzheimer's disease (AD) neuropathology, even in its early stages, affects the prefrontal lobes leading to executive dysfunction and mobility disturbances. Prefrontal cortex functions, including executive control, attention, and working memory, are known to decline with the progression of AD. In older adults, better performance on executive cognitive tasks is associated with greater activation of the left dorsolateral prefrontal cortex (dlPFC). Reduced activation within the dlPFC is believed to play a role in both the executive and physical functioning declines seen in AD, significantly contributing to loss of functional independence. In mild AD, an individual's state of executive functioning is a sensitive predictor of the ability to stand and walk safely, especially when performing additional cognitive tasks (i.e., dual tasking). Therefore, the investigators contend that by facilitating the excitability of the left dlPFC, some of the early cognitive and mobility impairments of AD may be reduced, ultimately leading to more functional independence, increased physical activity, and improved quality of life. tDCS provides a noninvasive means of facilitating the excitability of the prefrontal cortex and its connected neural networks, and thus holds promise as a therapy to improve the executive control of cognition and mobility in older adults with mild AD. tDCS modulates cortical excitability by passing low-level currents through electrodes placed upon the scalp over the dlPFC. These currents induce electrical fields within the brain that in turn polarize neuronal populations and alter their likelihood of firing. The research team demonstrated in older adults aged 65 years and older with executive dysfunction and slow gait that 10 sessions of 20-minutes of tDCS targeting the left dlPFC improved cognitive and physical functioning for at least two weeks following the intervention. Considerable evidence, including our preliminary studies, now suggest that multi-session tDCS interventions targeting the dlPFC may induce measurable and meaningful improvements in cognitive and/or mobility outcomes in relatively healthy adults and in those with mild-to-moderate executive dysfunction. Still, the size and duration of tDCS-induced benefits in older adults with executive dysfunction have not been established. Moreover, to date, tDCS delivery has not attempted to account for interpersonal differences in older adults, particularly the high inter-individual variance in skin, skull, brain, and cerebrospinal fluid and how each of these characteristics impacts the current flow. Such personalization is now possible with the current flow modeling the investigators propose. The overall aim of the study is to conduct a pilot, randomized sham-controlled trial to determine the feasibility and effects of a 10-session personalized tDCS intervention targeting the left dlPFC on cognitive function, dual task standing and walking, and other metrics of mobility in 24 older adults with mild AD living in supportive housing. The investigators will include personalized current flow modeling approach using baseline structural MRIs to determine the tDCS electrode placement and stimulation parameters to optimize current flow to each participant's brain. The investigators do not expect tDCS to revere the structural brain changes that result from AD, but instead maximize the function of remaining, intact brain neurons and frontal networks, and thereby improve functional outcomes in people suffering from the neurodegenerative process. The investigators hypothesize that, in older adults 65 years and older with mild AD, a personalized tDCS intervention targeting the left dlPFC, as compared to sham, will mitigate dual task costs to the control of gait and standing posture and enhance executive functioning.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Dementia, Presenile Alzheimer Dementia, Aging
Keywords
Aging

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
The investigators will conduct a single site, sham-controlled, double-blinded, randomized trial of tDCS. Participants will complete baseline cognitive and physical functioning assessments, as well as a structural MRI of the brain. They will then be assigned to a two-week, 10-session intervention of either personalized tDCS sham (i.e., control) stimulation, via permuted block randomization stratified by sex to ensure that equal number of men and women are randomized to each intervention arm.
Masking
ParticipantInvestigatorOutcomes Assessor
Masking Description
Study personnel administering tDCS and the participants will not be aware of tDCS intervention arm assignment. The investigators will ensure double-blinding by programming the tDCS software with intervention-specific stimulation codes, as supplied by personnel uninvolved in data collection prior to study initiation.
Allocation
Randomized
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Personalized tDCS
Arm Type
Experimental
Arm Description
Baseline MRIs will enable personalization of tDCS via current flow modeling for optimization to each participant with the goal of generating an average electric field of 0.25 V/m within their identified left dlPFC. The direct current delivered by any one electrode will not exceed 2.0 mA and the total amount of current from all electrodes will not exceed 4 mA. Each 20-minutes session will begin and end with a 60-second ramp up/down of current amplitude to maximize comfort.
Arm Title
Active-Sham
Arm Type
Sham Comparator
Arm Description
The investigators 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. This intervention will be optimized to each participant to deliver currents designed to not significantly influence their cortical tissue, but still mimic the cutaneous sensations induced by tDCS.
Intervention Type
Other
Intervention Name(s)
Personalized tDCS
Intervention Description
The participant will receive 10, 20-minutes sessions of personalized tDCS Monday-Friday, at approximately the same time of day, over two consecutive weeks.
Intervention Type
Other
Intervention Name(s)
Active-Sham
Intervention Description
The participant will receive 20, 20-minute sessions of active-sham stimulation Monday-Friday, at approximately the same time of day, over two consecutive weeks.
Primary Outcome Measure Information:
Title
Recruitment efficiency
Description
The number of residents that need to be screened in order to enroll one participant into the trial.
Time Frame
1 year
Title
Retention
Description
The percentage of enrolled participants who complete the trial.
Time Frame
1 year
Title
Blinding
Description
A blinding efficacy questionnaire will be used to record participant guesses of their assigned intervention (real or placebo), as well as the confidence of these guesses on a scale from 1=Not confident to 10=Extremely confident.
Time Frame
Immediately after intervention
Title
Montreal Cognitive Assessment (MoCA) total score
Description
This common test assesses global cognitive function. Maximum score on the MoCA is 30 points (minimum = 0), with higher scores associated with better outcomes.
Time Frame
Change from baseline to two-week follow-up
Title
Dual task gait speed
Description
This metric assesses the ability to control gait while performing a secondary cognitive task.
Time Frame
Change from baseline to two-week follow-up
Title
Dual task standing postural sway area
Description
This metric assesses the ability to control standing posture while performing a secondary cognitive task.
Time Frame
Change from baseline to two-week follow-up
Secondary Outcome Measure Information:
Title
Trail making test A-B
Description
This metric assesses cognitive executive function.
Time Frame
Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention
Title
Digit Span
Description
This common test assesses working memory.
Time Frame
Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention
Title
Digit Symbol Substitution Test
Description
This common test assesses sustained attention and motor speed.
Time Frame
Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention
Title
Category and Phonemic Fluency Test
Description
This common test assesses word retrieval.
Time Frame
Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention
Title
Hopkins Verbal Learning Test
Description
This common test assesses memory.
Time Frame
Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention
Title
Dual task stride time variability
Description
This metric assesses the ability to control gait while performing a secondary cognitive task.
Time Frame
Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention
Title
Dual task standing postural sway speed
Description
This metric assesses the ability to control standing posture while performing a secondary cognitive task.
Time Frame
Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention
Title
Timed Up-and-Go
Description
This metric assesses mobility.
Time Frame
Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention
Title
Five-day accelerometry-based physical activity
Description
This metric assesses the quantity and quality of habitual physical activity.
Time Frame
Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention
Title
Centers for Epidemiologic Studies Depression Scale
Description
This metric assesses mood.
Time Frame
Baseline, within 3 days after completion of the intervention, two weeks after completing the intervention

10. Eligibility

Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Men and women aged 65 and older living within supportive housing facilities Mild Alzheimer's disease (AD) defined by the combination of 1) at least mild cognitive impairment defined as a modified TICS score of ≤ 34, 2) informant-report of Instrumental Activities of Daily Living impairment as defined as a score of ≥ 6 on the NACC Functional Activities Questionnaire, and 3) a Clinical Dementia Rating score of 1. Exclusion Criteria: Inability to secure informant participation Unwillingness to cooperate or participate in the study protocol An inability to ambulate without the assistance of another person (canes or walkers allowed) A clinical history of stroke, Parkinson's disease or parkinsonian symptoms, multiple sclerosis, normal pressure hydrocephalus, or other neurological conditions outside of mild AD. Any report of severe lower-extremity arthritis or physician-diagnosis of peripheral neuropathy Use of antipsychotics, anti-seizure, benzodiazepines, or other neuroactive medications Severe depression defined by a Center for Epidemiologic Studies Depression scale score greater than 16 Any report of physician-diagnosis of schizophrenia, bipolar disorder, or other psychiatric illness Contraindications to MRI or tDCS, including reported seizure within the past two years, use of neuropsychological-active drugs, the risk of metal objects anywhere in the body, self-reported presence of specific implanted medical devices (e.g., deep brain stimulator, medication infusion pump, cochlear implant, pacemakers, 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
Peggy Gagnon
Phone
617-971-5303
Email
gagnon@hsl.harvard.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Kathryn Tasker
Phone
617-971-5351
Email
KathyTasker@hsl.harvard.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brad Manor, PhD
Organizational Affiliation
Hebrew SeniorLife
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hebrew Rehabilitation Center
City
Roslindale
State/Province
Massachusetts
ZIP/Postal Code
02131
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peggy Gagnon
Phone
617-971-5303
Email
gagnon@hsl.harvard.edu
First Name & Middle Initial & Last Name & Degree
Kathy Tasker
Phone
617-971-5351
Email
KathyTasker@hsl.harvard.edu
First Name & Middle Initial & Last Name & Degree
Brad Manor, PhD
First Name & Middle Initial & Last Name & Degree
Lewis Lipsitz, MD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
The HSL 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 longitudinal demographic, clinical, functional, physiologic, and brain imaging 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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Individualized Brain Stimulation to Improve Mobility in Alzheimer's Disease

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