Clinical trial NCT06821568: Home-Based Brain Stimulation for Motoric Cognitive Risk Syndrome
Official title: Long-term Home-based Transcranial Electrical Stimulation for Cognitive and Motor Function in Older Adults With an Increased Risk of Dementia: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Alzheimer Disease and Related Dementias
Cognition
Mobility Disability
Keywords: Anatomy
Anxiety
Atrophic
Behavioral
Brain
Brain Region
Cephalic
Cognitive
Communities
Dementia
Development
Dose
Double-Blind Method
Electric Stimulation
Enrollment
Evaluation
Exhibits
Exposure to
Frequencies
Future
Gait
Gait Speed
Genetic Crossing Over
Home
Impaired Cognition
Individual
Intervention
Intervention Studies
Magnetic Resonance Imaging
Measurable
Measures
Mood
Motor
Multi-Institutional Clinical Trial
Neuronal Plasticity
Outcome
Participant
Performance
Phase
Pilot Projects
Prefrontal Cortex
Randomized
Randomized Controlled Clinical Trials
Research
Resolution
Rest
Risk
Series
Site
Structure
Testing
Therapeutic
Time
Syndrome
Walking
Work
Arm
cerebral atrophy
Clinically relevant
cognitive task
Cost
Dementia Risk
Design
Executive Function
functional improvement
functional near infrared spectroscopy
Gray Matter
high risk
home test
improved
insight
late life
mental function
neural network
neuroimaging
noninvasive brain stimulation
normal aging
older adult
older men
older women
open label
primary endpoint
response
secondary outcome
smartphone application
transcranial direct current stimulation
trial design
walking speed
Alzheimer&#39;s Disease
Lead sponsor: Hebrew SeniorLife
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
name: Tel Aviv Medical Center
First posted: 2025-02-12
Enrollment: 128
Sex: ALL
Minimum age (years): 65
Maximum age (years): 90
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: The investigators will conduct a multi-site, sham-controlled, double-blinded, randomized trial of home-based tDCS with stimulation parameters tailored to target the anatomically defined left dlPFC of each participant. Participants will complete baseline cognitive and physical functioning assessments, as well as a structural MRI of the brain. After an initial open-label 2-week tDCS intervention, participants will be randomized into a tDCS arm (5 weekly tDCS sessions for 6 months), or a combination arm of 5 weekly tDCS sessions for 3 months before or after 5 weekly sessions of sham for 3 months via permuted block randomization stratified by sex to ensure that equal number of men and women are randomized to each intervention arm.
Primary purpose: TREATMENT

Brief summary: The objective of this study is to determine the effects of a 6-month, home-based personalized transcranial direct current stimulation (tDCS) intervention targeting the left dorsolateral prefrontal cortex on cognitive function, dual task standing and walking, and other metrics of mobility in older adults with motoric cognitive risk syndrome (MCR).

Detailed description: In older adults, motoric cognitive risk (MCR) is a pre-dementia transition state between "normal" aging and dementia. MCR is associated with impaired function within several brain networks that causes numerous symptoms including loss of memory, the ability to complete complex mental tasks, and the capacity to control one's walking and thus avoid falling and fall-related injuries. This study seeks to assess the short-term and long-term use of an investigational device called a transcranial direct current stimulation (tDCS).

tDCS is a noninvasive technology that enables selective modulation of brain network function, to provide multi-symptom relief to older adults with MCR. By using state-of-the-art technology to 1) utilize a personalized tDCS intervention via an established optimization approach using individual brain MRIs, and 2) complete stimulation in a home-based setting, this study is expected to result in the development of tDCS interventions that have maximal impact on daily life function within this population.

In this study, investigators will conduct a 9-month sham-controlled, double-blinded, multi-site trial in 128 older adults aged 65-90 years old with MCR. All enrolled participants will complete an open-label 2-week, 10-session tDCS intervention. During the open-label phase of the study, all participants will receive active tDCS. Then, participants will be randomly assigned into either the tDCS arm that receives five weekly tDCS sessions for 6 months, or a combination arm of five weekly tDCS sessions for 3 months before or after five weekly sessions of sham for 3 months. Sham treatment is similar to the study tDCS treatment, but omits the key therapeutic element of the treatment being studied. Participants in the combination arm will not know whether they are receiving tDCS or sham during the first or second 3-month period. Enrolled participants will complete assessments relating to cognition, mood, balance, and memory at baseline, after the 2-week open-label phase, after 3 and 6 months of tDCS, and again 3 months later. Once a week, participants will also complete a gait (walking) assessment at home. MRI scans will be performed at baseline and after completing 3 months of tDCS.

Eligibility criteria: Inclusion Criteria:

* Men and women
* Age 65-90 years
* Subjective cognitive complaints as defined by a 'Yes' response to "Do you feel that you have more problems with memory than most?" or a 'No' response to "is your mind as clear as it used to be?"
* Montreal Cognitive Assessment (MoCA) score ≥21
* Slow gait speed as measured by averaging two 4-Meter walks and defined as a usual walking speed one standard deviation below age and sex-adjusted means.
* Absence of significant disability as defined by the ability to walk over the instrumented gait mat unassisted (e.g., able to walk without any walking aids for at least 2 minutes non-stop) and preserved activities of daily living as defined by a score of less than 9 on the Functional Activities Questionnaire.
* Identification of an eligible informant
* Identification of a willing and able tDCS-administrator; i.e., a study partner to lead the administration of home-based transcranial direct current stimulation (tDCS)
* Access to reliable WiFi in the participant's home

Exclusion Criteria:

* Formal education less than the 8th grade
* Previous physician diagnosis of dementia
* Any current diagnosis of a major psychiatric disorder (e.g., schizophrenia, bipolar disorder, major depressive disorder)
* Evidence of moderate-to-severe depressive symptoms defined by a score of ≥9 on the 15-item Geriatric Depression Scale
* History of head trauma resulting in prolonged loss of consciousness
* History of fainting spells of unknown or undetermined etiology that might constitute seizures
* History of seizures, diagnosis of epilepsy, or immediate (first-degree relative) family history of epilepsy except for a single seizure of benign etiology (e.g. febrile seizures) in the judgment of a board-certified neurologist
* Hospitalization within the past three months due to acute illness, or as the result of a musculoskeletal injury significantly affecting gait or balance
* Any unstable medical condition or chronic (particularly) uncontrolled medical conditions that may cause a medical emergency in case of a provoked seizure (cardiac malformation, cardiac dysrhythmia, asthma, etc.) or study complication
* Substance use disorders within the past six months
* A hairstyle or headdress that prevents electrode contact with the scalp or would interfere with the stimulation (for example thick braids, hair weave, afro, wig)
* Chronic vertigo
* Myocardial infarction within the past 6 months
* Active cancer for which chemo-/radiation therapy is being received
* Legal blindness
* Visual hallucinations (history or self-report)
* Pacemaker
* Contraindications to MRI or tDCS, including unprovoked seizure within the past two years, risk of ferromagnetic objects anywhere in the body, self-reported presence of specific implanted medical devices (e.g., deep brain stimulator, medication infusion pump, cochlear implant, pacemaker, etc.), the presence of any active dermatological condition, such as eczema, on the scalp, etc. as outlined by current recommendations for noninvasive brain stimulation endorsed by the International Federation for Clinical Neurophysiology.
* History of REM sleep behavior disorder (RBD), often an early sign of Parkinson's disease
* Medications and medical history will be reviewed by the responsible covering physician and a decision about inclusion will be made based on the participant's past medical history, drug dose, history of recent medication changes or duration of treatment, and combination with other CNS active drugs.

Primary outcomes:
measure: Dual task cost to gait speed
timeFrame: Pre-randomization baseline; within three days of completing the initial open-label tDCS intervention; Month 3, Month 6; Month 9.
Secondary outcomes:
measure: Executive function composite score
timeFrame: Baseline, within three days of completing initial open-label tDCS intervention, Month 3, Month 6, & Month 9.
measure: Dual task gait speed
timeFrame: Baseline, within three days of completing initial open-label tDCS intervention, Month 3, Month 6, & Month 9.
measure: Preferred gait speed
timeFrame: Baseline, within three days of completing initial open-label tDCS intervention, Month 3, Month 6, & Month 9.
measure: The change in left prefrontal deoxygenated hemoglobin between standing and dual task walking
timeFrame: Baseline, within three days of completing initial open-label tDCS intervention, Month 3, Month 6, & Month 9.
measure: The change in left prefrontal deoxygenated hemoglobin between standing and usual walking
timeFrame: Baseline, within three days of completing initial open-label tDCS intervention, Month 3, Month 6, & Month 9.
measure: Left dorsolateral prefrontal cortex (dlPFC) gray matter volume
timeFrame: Baseline & Month 3
measure: Left dorsolateral prefrontal cortex (dlPFC) functional connectivity
timeFrame: Baseline & Month 3
measure: 7-day accelerometry-based physical activity
timeFrame: Baseline, within three days of completing initial open-label tDCS intervention, Month 3, Month 6, & Month 9.
Other outcomes:
Locations:
city: Roslindale
country: United States
facility: Hebrew Rehabilitation Center
state: Massachusetts
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
Study officials:
affiliation: Hebrew SeniorLife
name: Brad Manor, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tel-Aviv Sourasky Medical Center
name: Jeff Hausdorff, PhD
role: PRINCIPAL_INVESTIGATOR
References: