NCT07526740 · Medical University of South Carolina
Brain Stimulation and Cognitive Training for MCI
(RISE pilot)
What this study is about
This is a randomly assigned clinical trial of a treatment that combines non-invasive brain stimulation with computerized cognitive training (CCT) for people with mild cognitive impairment (MCI). The form of brain stimulation used in this study is accelerated intermittent theta burst stimulation (iTBS).
View original scientific description
This is a randomized clinical trial of a treatment that combines non-invasive brain stimulation with computerized cognitive training (CCT) for people with mild cognitive impairment (MCI). The form of brain stimulation used in this study is accelerated intermittent theta burst stimulation (iTBS). All participants receive the same amount of iTBS and are randomly assigned to engage in one of two types of CCT. The goals of the study are to see if this combined treatment is feasible and acceptable to people with MCI and whether combined iTBS and CCT improves memory, thinking skills, mood, and daily function.
Interventions
DEVICE
Accelerated iTBS
A MagVenture MagPro Transcranial Magnetic Stimulation (TMS) System with Brainsight neuronavigation will be used. All participants will receive active treatment: 12 sessions (3 min each) of iTBS on each of 3 treatment days within an 8-day span. A single session = 600 pulses of 50 Hz iTBS triplets delivered every 200ms in 2s trains repeated every 10s (8s inter-train interval) for 190s. Stimulation intensity is 120% resting motor threshold (rMT) delivered at the left dorsolateral prefrontal cortex. Total pulses = 21,600. Inter-session intervals will be approx. 15 min.
DEVICE
Computerized Cognitive Training
CCT will be delivered through the online BrainHQ platform. Participants will engage in adaptive visual speed of processing training during the 15-min breaks between iTBS sessions (11 sessions on each treatment day, total CCT time = 495 min).
DEVICE
Sham Computerized Cognitive Training
Sham CCT will be delivered through the online BrainHQ platform. Participants will engage in non-adaptive control games during the 15-min breaks between iTBS sessions (11 sessions on each treatment day, total sham CCT time = 495 min).
Primary outcome measures
Retention
Time frame: From enrollment to the end of study at week 6 (1-month post-treatment assessment).
Percent of participants who completed all study procedures(i.e., Week 0 pre-treatment assessments, all treatment sessions, and Week 2 and Week 6 follow-up assessments). This will be calculated as a binary count (1=yes, 0=no) of completers divided by the total number of participants.
Adherence
Time frame: On each of the 3 treatment days during Week 1
Percent of treatment sessions completed. This will be calculated as the number of full iTBS and CCT sessions completed by each participant divided by the prescribed number of sessions.
Acceptability
Time frame: Week 0 (1 week pre-treatment), Week 2 (1 week post-treatment)
Ratings of treatment acceptability on the Theoretical Framework of Acceptability (TFA) Questionnaire. The TFA is a self-report measure on which participants rate their perceptions of treatment acceptability via 5-point Likert-scale ratings on 8 items regarding the following: affective attitude, burden, perceived effectiveness, intervention coherence, self-efficacy, opportunity costs, ethicality, and general acceptability. Item scores will be averaged (ranging from 0-5), with higher scores indicating greater intervention acceptability.
Change in NIH Toolbox-Cognition Battery (NIHTB-CB) Fluid Composite
Time frame: Week 0 (1 week pre-treatment), Week 2 (1 week post-treatment), and Week 6 (4 weeks post-treatment)
The NIHTB-CB is a performance-based, iPad-administered \~30-minute suite of 7 tests that ascertain abilities in different cognitive domains (e.g. executive function, episodic memory, working memory, processing speed, language). It was developed using advanced psychometric techniques to minimize measurement error and produces normed subtest and composite scores. We will use the fully-corrected T-score (range T=0-100; Mean T=50, SD=10; higher scores indicate better cognition) of the Fluid Cognition Composite (normed for age and years of education).
Change in Preclinical Alzheimer's Cognitive Composite (Mayo-PACC) Z-score
Time frame: Week 0 (1 week pre-treatment), Week 2 (1 week post-treatment), and Week 6 (4 weeks post-treatment)
The Mayo-PACC is a composite derived from a brief battery of three neuropsychological tests of verbal episodic memory, processing speed, and semantic fluency. Z-scores will be computed for each test using a cognitively unimpaired normative reference; these will be averaged to create a single composite Z-score (Mean Z=0, SD=1; higher scores indicate better cognition).
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- Age 60-85 (inclusive).
- English as a first/primary language.
- Adequate sensorimotor function and verbal expressive abilities to complete all assessments.
- Must have a co-participant (e.g. spouse, adult child or relative, sibling, cohabitator, friend, caregiver) who has at least weekly in-person contact with the participant and is willing to participate in the study as a collateral informant.
- Meets the following requirements for current and prior medications and treatments:
- Is on fixed pharmacotherapy (i.e. stable dose of medication/s) for ≥ 4 weeks before enrollment. This includes, but is not limited to, cholinesterase inhibitors, NMDA receptor antagonists, and antidepressants.
- Anti-amyloid monoclonal antibody therapy for AD/MCI:
- Prior treatment is permitted if last infusion occurred ≥ 8 weeks before enrollment.
- Current treatment is permitted if the dose has been stable for ≥ 12 weeks before enrollment, with no planned dose change during study participation.
- Prior TMS treatment is permitted if the last stimulation session was ≥ 24 weeks before enrollment.
- Documented diagnosis of MCI per NIA-AA criteria or Mild Neurocognitive Disorder per DSM-5 criteria by a healthcare provider within the past year, with a presumed etiology of possible or probable AD 7. Met actuarial neuropsychological criteria for MCI43 within the past year (i.e. ≥2 impaired scores within one cognitive domain, or ≥1 impaired scores in ≥3 domains, where an impaired score is defined as ≤16th percentile using appropriate demographically-corrected norms).
Exclusion criteria
- Telephone Interview for Cognitive Status (TICS) score of ≤ 22 suggestive of dementia.
- Prior diagnosis of Dementia (NIA-AA) or Major Neurocognitive Disorder (DSM-5).
- Daily/weekly anticholinergic or sedative use. Stimulants may be allowed pending investigator review.
- History of significant or unstable condition/s or treatments for these condition/s that may impact cognition (as determined by the study investigators) such as significant cardiac (e.g. heart failure), infectious (e.g. HIV, urinary tract infection), or metabolic disease (e.g. labile diabetes), cancer (e.g. brain cancer, chemotherapy-induced cognitive impairment), severe mental illness (e.g., bipolar disorder, psychoses), alcohol or substance use disorder, developmental disorder (e.g. autism spectrum disorder, intellectual disability), or other neurologic disease (e.g. movement disorder, multiple sclerosis, moderate to severe brain injury, seizures).
- Plan to initiate treatment for AD/MCI with monoclonal antibody therapy during study participation.
- For those currently receiving monoclonal antibody therapy, documented history of clinically significant amyloid-related imaging abnormalities (ARIA) in their medical record.
- Current use of any implanted brain stimulation device.
- Enrolled in a clinical trial or has received an investigational medication or device in the last 30 days that may impact cognition or mood.
- MRI contraindications (e.g., ferromagnetic implants, claustrophobia).
- Unable or unwilling to engage in BrainHQ activities.
- TMS contraindications (e.g., ferromagnetic implants, conditions or treatments that lower seizure threshold, taking medications that have short half-lives) or no identifiable motor threshold.
Where
- Charleston, South Carolina
Collaborators
National Institutes of Health (NIH), National Institute on Aging (NIA)
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced May 22, 2026 · Source of record for eligibility and locations