Noninvasive Brain Stimulation for Mild Cognitive Impairment

NCT03331796 | Completed Results FDA Device

• 2 other identifiers: TAY0003AGGR01AG055526
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to test the efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) as a treatment for Mild Cognitive Impairment (MCI). Participants will be randomly assigned to one of three treatment groups: Group 1: Active Dorsolateral Prefrontal Cortex (DLPFC) rTMS; Group 2: Active Lateral Parietal Cortex (LPC) rTMS; and Group 3: Inactive rTMS (Placebo) control (evenly split between each coil location). Participation in the study takes approximately 7 ½ months-including a 2-to 4-week treatment phase (20 rTMS sessions) and a 6-month follow-up phase.

Conditions

Mild Cognitive Impairment; Mild Neurocognitive Disorder; Cognitive Decline; Mental Deterioration; Cognitive Dysfunction; Memory Decline; Memory Loss; Memory Impairment

Keywords

mild cognitive impairment; tms; rtms; transcranial magnetic stimulation; noninvasive brain stimulation; non-pharmacological

Outcome Measures

Primary Outcomes (1)

• Total Number of Words Correctly Recalled, List Learning, California Verbal Learning Test-II, Assessed 1 Week After Intervention and Adjusted for Baseline Performance

  The California Verbal Learning Test, Second edition (CVLT-II) is a memory task that yields several indices of the ability to learn a list of semantically related words and remember the list after a delay interval. The target list ("List A") of the CVLT-II contains 16 words. There are 5 orally presented learning trials; each is followed by immediate recall of the words in any order. The total number of words correctly recalled on the 5 list-learning trials was computed (range = 0 to 80). Higher values represent a better outcome.

  1 week after completing the 20-session intervention, which was typically 4 weeks after starting the intervention.

Secondary Outcomes (16)

• Total Number of Words Correctly Recalled, List Learning, California Verbal Learning Test-II, Assessed 3 Months After Intervention and Adjusted for Baseline Performance

  3 months after completing the 20-session intervention (acceptable window for assessment: 76-104 days after the final intervention session)

• California Verbal Learning Test-II (CVLT-II) Semantic Clustering Score, 1 Week After Intervention and Adjusted for Baseline Performance

  1 week after completing the 20-session intervention, which was typically 4 weeks after starting the intervention.

• Total Number of Words Correctly Recalled During the "Long Delay Free Recall" Component of the California Verbal Learning Test-II (CVLT-II), Assessed 1 Week After Intervention and Adjusted for Baseline Performance

  1 week after completing the 20-session intervention, which was typically 4 weeks after starting the intervention

• Depressive Symptoms, as Measured by the Geriatric Depression Scale (GDS), Assessed 1 Week After Intervention and Adjusted for Baseline Performance

  1 week after completing the 20-session intervention, which was typically 4 weeks after starting the intervention.

• Everyday Functional Outcomes, as Measured by the Everyday Cognition (ECog) Questionnaire (Participant Version) Completed 1 Week After Intervention

  1 week after completing the 20-session intervention, which was typically 4 weeks after starting the intervention

Study Arms (3)

Active repetitive transcranial magnetic stimulation (rTMS) (Bilateral DLPFC)

EXPERIMENTAL

One-third of participants will receive active rTMS to the right and left dorsolateral prefrontal cortex (DLPFC).

Device: Active rTMS (Bilateral DLPFC)

Active repetitive transcranial magnetic stimulation (rTMS) (Bilateral LPC)

EXPERIMENTAL

One-third of participants will receive active rTMS to the right and left lateral parietal cortex (LPC).

Device: Active rTMS (Bilateral LPC)

Placebo repetitive transcranial magnetic stimulation (rTMS) (Inactive)

PLACEBO COMPARATOR

One-third of participants will receive placebo/inactive rTMS, either to the DLPFC or the LPC. Those receiving placebo rTMS will serve as the control group.

Device: Placebo rTMS (Inactive)

Interventions

Active rTMS (Bilateral DLPFC) DEVICE

TMS Stimulation Parameters for the active DLPFC rTMS intervention group will be: 10 Hz, 4-second train duration and 11-second inter-train interval. During each session, 2,000 pulses will be applied for each hemisphere (for a total of 4,000 pulses per session). Participants will receive 20 sessions (1 or 2 sessions per day, M-F).

Active repetitive transcranial magnetic stimulation (rTMS) (Bilateral DLPFC)

Active rTMS (Bilateral LPC) DEVICE

TMS Stimulation Parameters for the active LPC rTMS intervention group will be: 10 Hz, 4-second train duration and 11-second inter-train interval. During each session, 2,000 pulses will be applied for each hemisphere (for a total of 4,000 pulses per session). Participants will receive 20 sessions (1 or 2 sessions per day, M-F).

Active repetitive transcranial magnetic stimulation (rTMS) (Bilateral LPC)

Placebo rTMS (Inactive) DEVICE

For the Placebo rTMS (Inactive) group, the participant will wear scalp electrodes through which a low voltage, low electric current (2-20mA at no more than 100V) is passed to mimic the sensation of receiving actual rTMS. Participants will receive 20 sessions (1 or 2 sessions per day, M-F).

Placebo repetitive transcranial magnetic stimulation (rTMS) (Inactive)

Eligibility Criteria

• Age: 55 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosed with amnestic Mild Cognitive Impairment (aMCI);
• Stable medications (including any dementia-related meds) for at least 4 weeks prior to Baseline;
• Geriatric Depression Scale score less than 6;
• Ability to obtain a motor threshold, determined during the screening process;
• Study partner available; living situation enables attendance at clinic visits;
• Visual and auditory acuity adequate for neuropsychological testing;
• Good general health with no diseases expected to interfere with the study;
• Participant is not pregnant or of childbearing potential (i.e. women must be 2 years post-menopausal or surgically sterile);
• Modified Hachinski Ischemic score less than or equal to 4;
• Agree to DNA extraction for single nucleotide polymorphism (SNP) genotyping;
• Able to understand study procedures and comply with them for the entire length of the study.

You may not qualify if:

• Prior exposure to rTMS within the past 12 months;
• Magnetic field safety concern such as a cardiac pacemaker, cochlear implant, implanted device in the brain (deep brain stimulation), or metal fragments or foreign objects in the eyes, skin or body;
• Any significant neurological disease other than suspected incipient Alzheimer's disease;
• Unstable cardiac disease or recent (\< 3 months previous) myocardial infarction. Any significant systemic illness or unstable medical condition that could lead to difficulty with protocol adherence;
• History of epilepsy or repetitive seizures, as determined by patient report or chart review;
• History of a medical condition or current use/abuse of medications and substances that increase the risk of a seizure, specifically:
• Traumatic brain injury within 2 months that would increase the risk for seizure;
• Unable to safely withdraw, at least 4 weeks prior to Baseline, from medications that substantially increase the risk of having seizures (for example: theophylline, clozapine, and methylphenidate).
• Current or past history of a mass lesion, cerebral infarct, or other noncognitive active neurological disease that would increase the risk for seizure.
• Stimulant abuse within the previous 90 days. Cocaine and abuse of amphetamine and methylphenidate are associated with an increased risk of seizures;
• Major depression or bipolar disorder (DSM-IV) within the past 1 year, or psychotic features within the last 3 months that could lead to difficulty with protocol adherence;
• Taking sedative hypnotics or medications with anti-cholinergic properties and unable to withdraw at least 4 weeks prior to Baseline;
• Current alcohol or substance abuse (not including caffeine or nicotine) within the past 1 year, as determined by chart review, participant or study partner report, or greater than "moderate" alcohol use defined by the Quantity-Frequency-Variability Index (Cahalan, Cisin, \& Crossley, 1969);
• Any contraindications for magnetic resonance imaging (MRI) studies, e.g. severe claustrophobia, weight above 350 lb maximum allowed by MRI scanner, pregnancy;
• Participation in another concurrent clinical trial;

Sponsors & Collaborators

• Palo Alto Veterans Institute for Research: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

VA Palo Alto Health Care System

Palo Alto, California, 94304, United States

Location

Related Publications (2)

• Liao X, Li G, Wang A, Liu T, Feng S, Guo Z, Tang Q, Jin Y, Xing G, McClure MA, Chen H, He B, Liu H, Mu Q. Repetitive Transcranial Magnetic Stimulation as an Alternative Therapy for Cognitive Impairment in Alzheimer's Disease: A Meta-Analysis. J Alzheimers Dis. 2015;48(2):463-72. doi: 10.3233/JAD-150346.

  PMID: 26402010 BACKGROUND

• Taylor JL, Hambro BC, Strossman ND, Bhatt P, Hernandez B, Ashford JW, Cheng JJ, Iv M, Adamson MM, Lazzeroni LC, McNerney MW. The effects of repetitive transcranial magnetic stimulation in older adults with mild cognitive impairment: a protocol for a randomized, controlled three-arm trial. BMC Neurol. 2019 Dec 16;19(1):326. doi: 10.1186/s12883-019-1552-7.

  PMID: 31842821 DERIVED

MeSH Terms

Conditions

Cognitive Dysfunction; Neurocognitive Disorders; Memory Disorders

Condition Hierarchy (Ancestors)

Cognition Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Smaller numbers of subjects were enrolled than originally proposed. Reasons included: a protracted start-up, low enrollment during Years 1 and 2, the cessation of TMS intervention visits and new enrollment during the COVID-19 pandemic in Year 3, and National Institute on Aging's decision to terminate the award in Year 4.

Results Point of Contact

• Title: Joy L Taylor, PhD
• Organization: Veterans Affairs Palo Alto Health Care System

joyt@stanford.edu

650-776-3385

Study Officials

• Joy L Taylor, Ph.D.

  Stanford/VA Aging Clinical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 18, 2017
• First Posted: November 6, 2017
• Study Start: June 15, 2018
• Primary Completion: December 19, 2022
• Study Completion: March 28, 2023
• Last Updated: September 3, 2025
• Results First Posted: September 3, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)