NCT05992831 · Medical University of South Carolina
Transcranial Magnetic Stimulation for MCI
(PUSH2)
What this study is about
The goal of this phase II study is to establish the dose-response curves of a safe and clinically feasible non-invasive brain stimulation technique (accelerated Transcranial Magnetic Stimulation (TMS)) to improve both depression and cognitive function in Mild Cognitive Impairment (MCI) patients with comorbid depression. It is known that TMS can effectively treat depression.
View original scientific description
The goal of this phase II study is to establish the dose-response curves of a safe and clinically feasible non-invasive brain stimulation technique (accelerated Transcranial Magnetic Stimulation (TMS)) to improve both depression and cognitive function in Mild Cognitive Impairment (MCI) patients with comorbid depression. It is known that TMS can effectively treat depression. Identifying the right dose of accelerated TMS in MCI patients is necessary prior to designing subsequent trials to determine efficacy. These results will inform future clinical trials of accelerated TMS for MCI, with the long-term goal of developing an efficacious treatment to prevent dementia.
Interventions
DEVICE
Accelerated iTBS
The investigators will treat participants with accelerated intermittent theta burst stimulation. iTBS will be delivered via a MagVenture MagPro TMS System with a Cool-B65 coil, targeting to direct the stimulation to the left dorsolateral prefrontal cortex (l-dlPFC). The investigators will use a standard resting motor threshold (rMT) determination to determine the TMS dose. Treatment will be delivered at 120% of the motor threshold. Total treatment time will be controlled; all participants will perceive receiving active treatment for 10 3-min sessions with 10-15 min inter-session intervals, resulting in a 3-hour treatment day. At pre-treatment, a focal electrical sham will be individually titrated to participant tolerability. Participants then receive an individualized level of sham stimulation throughout treatment, to bolster the blind. Participants will be told that they will be receiving different doses throughout the treatment day, again to maintain the integrity of the blind.
DEVICE
Sham Comparator
To achieve adequate blinding, participants will go through the same number of sessions per day irrespective of the active and/or sham dose-step combination to which they are assigned. Sham sessions will be assigned in random order over the 10 sessions. The sequence of active and/or sham sessions for each treatment day is assigned a random code that is entered into the TMS system by the coordinator to maintain the integrity of the blind.
Primary outcome measures
Change in Geriatric Depression Scale (GDS) raw score
Time frame: Week 0 (1 week pre-treatment), Week 3 (1 week post-treatment), Week 10 (8 weeks post-treatment), and Week 26 (6 months post-treatment)
The GDS is a \~3 minute self-report questionnaire of depression symptoms to which respondents answer yes/no (range=0-30, where higher scores indicate greater depression severity). Co-Participants will complete an informant-reported short form.
Change in NIH Toolbox-Cognition Battery (NIHTB-CB) Fluid Composite
Time frame: Week 0 (1 week pre-treatment), Week 3 (1 week post-treatment), Week 10 (8 weeks post-treatment), and Week 26 (6 months post-treatment)
The NIHTB-CB is a performance-based, iPad-administered \~30-minute suite of 7 tests that ascertain abilities in different cognitive domains (i.e. 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 indicating better cognition) of the Fluid Cognition Composite (normed for age, sex, years of education, and race/ethnicity) to more accurately reflect global, dynamic thinking abilities that reflect the presence of disease or the impact of interventions, and not premorbid influences on test scores.
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
- i. Age 60-85 (inclusive). ii. English as a first/primary language. iii. Adequate sensorimotor function and verbal expressive abilities to complete all assessments. iv. 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. v. Is on fixed pharmacotherapy (i.e. a stable dose of medication/s) for at least 4 weeks prior to enrollment. Cholinesterase inhibitors, NMDA receptor antagonists, and antidepressants are allowed if on a stable regimen for at least 4 weeks prior to enrollment. Prior treatment with anti-amyloid monoclonal antibody therapy is acceptable if last infusion was at least 8 weeks prior to enrollment. Prior TMS treatment is acceptable if last stimulation session was at least 24 weeks prior to enrollment. vi. A documented diagnosis of MCI per NIA-AA criteria or Mild Neurocognitive Disorder per DSM-5 criteria by a healthcare provider within the past 2 years, with a presumed etiology of either (or both): vi.a Possible or probable AD vi.b Chronic cerebrovascular disease (CVD), specifically small vessel disease as defined in STRIVE-2 which includes small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, cerebral micro bleeds, cortical superficial siderosis, or cortical cerebral microinfarcts. . vii. Met actuarial neuropsychological criteria for MCI within the past 2 years (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). viii. Any lifetime depression, as defined by current or past Major Depressive Disorder per DSM-5.
Exclusion criteria
- i. A TICS score of ≤ 19 suggestive of dementia. ii. Prior diagnosis of Dementia (NIA-AA) or Major Neurocognitive Disorder (DSM-5). iii. Daily/weekly anticholinergic or sedative use. Stimulants may be allowed pending investigator review. iv. 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), 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). v. Current treatment for AD/MCI with monoclonal antibody therapy or plan to initiate treatment within three months of enrollment. vi. Current use of any implanted brain stimulation device. vii. Enrolled in a clinical trial or has received an investigational medication or device in the last 30 days. viii. MRI contraindications (e.g., ferromagnetic implants, claustrophobia) ix. TMS contraindications (e.g., ferromagnetic implants, conditions or treatments that lower seizure threshold, taking medications that have short half-lives, no identifiable motor threshold). x. Current alcohol or substance use disorder, bipolar disorder, schizophrenia spectrum or other psychotic disorder, suicidal/homicidal intent within the past month, or any suicide attempts within the past year.
Where
- Charleston, South Carolina
Collaborators
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 Apr 2, 2026 · Source of record for eligibility and locations