Using brain stimulation to improve cognitive function and depression in older adults with mild cognitive impairment

Transcranial Magnetic Stimulation for MCI: A Phase II Dose-Response Study

This study is testing if a special brain stimulation treatment can help older adults with mild cognitive impairment and depression feel better and think more clearly.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 60 Years to 85 Years
• Sex: All
• Sponsor: Medical University of South Carolina (other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Charleston, South Carolina)
• Trial ID: NCT05992831 on ClinicalTrials.gov

What this trial studies

This phase II study aims to establish the dose-response curves for accelerated Transcranial Magnetic Stimulation (TMS) in patients aged 60-85 with Mild Cognitive Impairment (MCI) and comorbid depression. The study will manipulate the total number of active pulses delivered during TMS sessions to determine the optimal dosing for improving both cognitive function and depressive symptoms. Participants will receive either active TMS or a sham treatment, with the goal of informing future trials on the efficacy of this non-invasive brain stimulation technique. The findings will help develop effective treatments to prevent dementia in this population.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 60-85 with a documented diagnosis of Mild Cognitive Impairment and comorbid depression.

Not a fit: Patients with severe cognitive impairment or those not meeting the eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to improved cognitive function and reduced depression in patients with Mild Cognitive Impairment.

How similar studies have performed: Previous studies have shown that TMS can effectively treat depression, but this specific approach in MCI patients is novel.

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. 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 this trial is running

Charleston, South Carolina

• Medical University of South Carolina — Charleston, South Carolina, United States (RECRUITING)

Study contacts

• Principal investigator: Andreana Benitez, PhD — Medical University of South Carolina
• Study coordinator: Andreana Benitez, PhD

Conditions: Mild Cognitive Impairment, Depression, &#34, mild cognitive impairment&#34, , Depression