Transcranial Magnetic Stimulation for MCI (PUSH2)
Mild Cognitive Impairment, Depression

About this trial
This is an interventional treatment trial for Mild Cognitive Impairment
Eligibility Criteria
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. 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 MCI51 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. Major Depressive Disorder of at least moderate severity per DSM-5 and a HAM-D Total ≥ 17. Exclusion Criteria: i. A TICS score of ≤ 22 suggestive of dementia and a PHQ-9 score of 0-9, indicating the absence of major depressive disorder. 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. Cholinesterase inhibitors, NMDA receptor antagonists, and antidepressants are allowed if on a stable regimen for at least 4 weeks prior to enrollment. 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. Past or current treatment for AD/MCI with monoclonal antibody therapy. vi. Enrolled in a clinical trial or has received an investigational medication or device in the last 30 days. vii. MRI and TMS contraindications (e.g. ferromagnetic implants, claustrophobia, conditions or treatments that lower seizure threshold, taking medications that have short half-lives, no identifiable motor threshold). viii. 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.
Sites / Locations
- Medical University of South Carolina
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Sham Comparator
Experimental
Experimental
Experimental
Experimental
Experimental
Dose Step 1 - 0 Active Accelerated iTBS Sessions
Dose Step 2 - 12 Active Accelerated iTBS Sessions
Dose Step 3 - 24 Active Accelerated iTBS Sessions
Dose Step 4 - 36 Active Accelerated iTBS Sessions
Dose Step 5 - 48 Active Accelerated iTBS Sessions
Dose Step 6 - 60 Active Accelerated iTBS Sessions
Participant will receive 10 sessions of accelerated iTBS on each of 6 treatment days, including 0/10 active sessions and 10/10 sham sessions per day for a total of 0 active sessions
Participant will receive 10 sessions of accelerated iTBS on each of 6 treatment days, including 2/10 active sessions and 8/10 sham sessions per day for a total of 12 active sessions (7,200 active pulses).
Participant will receive 4/10 active sessions and 6/10 sham sessions per day for a total of 24 active sessions (14,400 active pulses).
Participant will receive 6/10 active sessions and 4/10 sham sessions per day for a total of 36 active sessions (21,600 active pulses).
Participant will receive 8/10 active sessions and 2/10 sham sessions per day for a total of 48 active sessions (28,800 active pulses).
Participant will receive 10/10 active sessions and 0/10 sham sessions per day for a total of 60 active sessions (36,000 active pulses).