Neurostimulation for Cognitive Enhancement in Alzheimer's Disease

NCT04404153 | Completed DMC FDA Device

• 2 other identifiers: 2020-11274R01AG068167
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The prevalence of Alzheimer's Disease (AD) is rising, but existing medications provide only modest control of cognitive decline and associated symptoms, and novel therapies are urgently needed. This randomized sham-controlled trial will determine if an innovative low-risk remotely-supervised transcranial Direct Current Stimulation (tDCS) applied over the area of the dorsolateral prefrontal cortex for 30 minutes at the intensity of 2 mA five times per week for 6 months at home can improve cognitive performance and symptoms and modulate neuroimaging markers of neuroplasticity in 100 patients with mild to moderate AD. If effective, this novel intervention can substantially enhance AD symptom management at home, improve quality of life of AD patients and their families, and reduce burden associated with this debilitating illness.

Conditions

Alzheimer Disease; Dementia

Keywords

Alzheimer's Disease; transcranial direct current stimulation (tDCS)

Outcome Measures

Primary Outcomes (1)

• Global Cognitive Performance

  Change in The Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) was developed as an outcome measure for dementia interventions; its primary purpose was to be an index of global cognition in response to therapies. It assesses multiple cognitive domains across 11 items: Word Recall Task, Naming Objects and Fingers, Following Commands, Constructional Praxis, Ideational Praxis, Orientation, Word Recognition Task, Remembering Test Directions, Spoken Language, Comprehension and Word-Finding Difficulty. The score ranges from 0 to 70. A 4-point ADAS-cog change at 6 months is clinically meaningful.

  Baseline, at 6 months (immediately after the 6-month intervention)

Secondary Outcomes (8)

• Multiple-Domain Cognitive Dysfunction

  Baseline, at 6 months (immediately after the 6-month intervention), at 7 months (1 month post-intervention) and 9-months (3 months post-intervention).

• Executive control/spatial selective attention

  Baseline, at 6 months (immediately after the 6-month intervention), at 7 months (1 month post-intervention) and 9-months (3 months post-intervention).

• Quality of Life Scale

  Baseline, at 6 months (immediately after the 6-month intervention), at 7 months (1 month post-intervention) and 9-months (3 months post-intervention).

• Depressive Symptoms

  Baseline, at 6 months (immediately after the 6-month intervention), at 7 months (1 month post-intervention) and 9-months (3 months post-intervention).

• Tolerability of the study intervention: number of side effects and adverse events

  Baseline, at 6 months (immediately after the 6-month intervention), at 7 months (1 month post-intervention) and 9-months (3 months post-intervention).

Other Outcomes (2)

• Structural Neuroplasticity

  Baseline, at 6 months (immediately after the 6-month intervention) and 9-months (3 months post-intervention).

• Durability of Global Cognitive Performance

  Baseline and 9-months (3 months post-intervention).

Study Arms (2)

Active tDCS

EXPERIMENTAL

The active tDCS will involve 30-minutes of direct current at intensity of 2 milliamperes (mA).

Device: tDCS device model Soterix mini-CT (Soterix Medical Inc., New York, NY) programed to deliver active tDCS.

Sham tDCS

SHAM COMPARATOR

Sham stimulation consists of the direct current ramped up to 2mA over 30 seconds, ramped down over 30 seconds and stay at 0 current for the remaining application period.

Device: tDCS device model Soterix mini-CT (Soterix Medical Inc., New York, NY) programed to deliver sham tDCS.

Interventions

tDCS device model Soterix mini-CT (Soterix Medical Inc., New York, NY) programed to deliver active tDCS. DEVICE

At-home remotely supervised tDCS delivered over the dorsolateral prefrontal cortex with the anode on the left, cathode on the right, at an intensity of 2 mA, delivered for 30 minutes five times per week (Monday-Friday) for 26 weeks (6 months).

Active tDCS

tDCS device model Soterix mini-CT (Soterix Medical Inc., New York, NY) programed to deliver sham tDCS. DEVICE

Sham treatment will consist of the current ramped up to 2mA over 30 seconds, ramped down over 30 seconds and stay at 0 current for the remaining time of the 30-minute application period five times per week (Monday-Friday) for 26 weeks (6 months).

Sham tDCS

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Community-dwelling male or female of age 60 and older
• AD diagnosed by neurologists or geriatricians at our dementia and geriatric clinical sites. Clinicians will review the medical records of all potential cases to ensure the patients meet established clinical criteria for AD, and also examine individuals as needed to further establish the diagnosis. Mild-to moderate stage AD as determined by study clinicians using the Clinical Dementia Rating Scale (CDR). The CDR is a 5-point scale used to characterize six domains of cognitive and functional performance applicable to AD: Memory, Orientation, Judgment \& Problem Solving, Community Affairs, Home \& Hobbies, and Personal Care. The necessary information to make each rating is obtained through a semi-structured interview of the patient and a reliable informant (e.g., family member). A CDR score of 0.5 or 1 is rated as mild severity and a score of 2 is rated as moderate severity. The investigators selected mild to moderate AD patients as our target population as they are the most prevalent AD severity group referred to our clinics, increasing generalizability. This mild to moderate AD group is also most likely to be cared for in the community and at home, in contrast to more advanced or severe AD stages, which are more prevalent in institutional settings (and will be the focus of our future studies)
• If on dementia medication regimen, the regimen is stable for at least 4 weeks prior to enrollment. The investigators will not restrict clinicians from starting, adjusting or stopping dementia medications over the intervention period in keeping with the pragmatic nature of our trial, but will account for medications in both groups in our analysis
• Able to speak and understand English or Spanish at a level sufficient undergo the study procedures and testing protocols
• Able to provide Informed Consent (or able to provide assent with a legal surrogate providing informed consent.)

You may not qualify if:

• Unstable medical or major psychiatric illnesses or unstable treatments for medical or major psychiatric illnesses. Any medical or psychiatric diagnosis is permitted as long as it has been clinically stable for at least 3 months, reflected in part by stability of treatments for at least 3 months, and is expected on the basis of clinical judgment to be in a stable phase that will likely extend for 6 months
• History of head trauma, seizures, brain surgery, stroke or cancer affecting head, metal implants in the head or neck, compromised integrity or sensitivity of the skin at or near locations where electrodes will be placed (e.g., eczema, severe rashes, blisters, open wounds, burn including sunburns, cuts or irritation)
• Currently participating in another intervention study or using neurostimulation device
• Must not be currently receiving or have received (or completed) within the past 3 months any monoclonal antibody treatment for Alzheimer's

Sponsors & Collaborators

• Albert Einstein College of Medicine: lead
• MJHS Institute for Innovation in Palliative Care: collaborator
• Stony Brook University: collaborator
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

Related Publications (1)

• Gulley E, Verghese J, Blumen HM, Ayers E, Wang C, Portenoy RK, Zwerling JL, Weiss E, Knotkova H. Neurostimulation for cognitive enhancement in Alzheimer's disease (the NICE-AD study): a randomized clinical trial. Neurodegener Dis Manag. 2021 Aug;11(4):277-288. doi: 10.2217/nmt-2020-0061. Epub 2021 Jul 9.

  PMID: 34240627 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease; Dementia

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Joe Verghese, MD

  Stony Brook University

  PRINCIPAL INVESTIGATOR

• Lara Dhingra, PhD

  Metropolitan Jewish Health System

  PRINCIPAL INVESTIGATOR

• Mirnova Ceide, MD

  Albert Einstein College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2020
• First Posted: May 27, 2020
• Study Start: March 25, 2021
• Primary Completion: October 28, 2025
• Study Completion: February 19, 2026
• Last Updated: March 6, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)