Plasticity Using Stimulation and Habit: A Pilot Open-label rTMS Study for MCI

High-dose Accelerated Repetitive Transcranial Magnetic Stimulation to Cognitive Control Neurocircuitry in Mild Cognitive Impairment: A Safety and Feasibility Study

Sponsors

Lead Sponsor: Medical University of South Carolina

Source Medical University of South Carolina
Brief Summary

The goal of this pilot study is to determine whether a high-dose form of non-invasive brain stimulation is a promising and safe treatment for Mild Cognitive Impairment (MCI). Transcranial magnetic stimulation (TMS) is an FDA approved treatment for depression. In studies of TMS for depression and other disorders, individuals have experienced improved cognitive function. Thus, the current study is testing whether TMS is safe, feasible and effective in improving cognition in individuals with MCI.

Overall Status Not yet recruiting
Start Date September 1, 2020
Completion Date October 1, 2021
Primary Completion Date August 30, 2021
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
Presence of clinically significant structural brain change on T1- and T2-weighted Magnetic Resonance Imaging (MRI) Baseline prior to treatment and at follow-up within 1 week post-treatment
Change from Baseline global cognition, as measured by the Montreal Cognitive Assessment (MoCA) Baseline prior to treatment and at follow-up within 1 week post-treatment
Change in the review of systems criteria compared to baseline Baseline prior to treatment and at follow-up within 1 week post-treatment
Patient perception of treatment acceptability One questionnaire per day at the end each of the three treatment days
Retention rate Baseline prior to treatment and at follow-up within 1 week post-treatment
Secondary Outcome
Measure Time Frame
Change from Baseline depression, as measured by the Hamilton Depression Rating Scale (HAM-D) Baseline prior to treatment and at follow-up within 1 week post-treatment
Change from Baseline depression, as measured by the Geriatric Depression Scale (GDS) Baseline prior to treatment and at follow-up within 1 week post-treatment
Enrollment 20
Condition
Intervention

Intervention Type: Device

Intervention Name: High-dose accelerated rTMS

Description: A MagVenture MagPro Transcranial Magnetic Stimulation (TMS) System will be utilized. All participants will receive open-label treatment for approximately eight, 3-minute sessions of intermittent theta burst rTMS on each of three days within an eight-day span. A single session = 600 pulses at 120% rMT, intermittent Theta Burst Stimulation (iTBS) triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 s to left dorsolateral prefrontal cortex. Total pulses = 14,400. To enable adherence and retention, the days do not need to be contiguous. Same day sessions will be separated by 10-15 minutes, but more accounting for participant comfort.

Arm Group Label: High-dose accelerated rTMS

Eligibility

Criteria:

Inclusion Criteria:

- Age 65-85

- English as a first/primary language

- Has been diagnosed with MCI by a healthcare provider within the past two years per National Institute on Aging - Alzheimer's Association (NIA-AA) criteria: (1) Concern regarding cognitive decline reported by patient, informant, or clinician, (2) Objective evidence of impairment for age in 1+ cognitive domains, typically memory, (3) Preserved independent function, (4) no dementia.

- Has met actuarial neuropsychological criteria for amnestic MCI: (1) ≥2 impaired scores (i.e. ≤16th %ile) within one cognitive domain, or (2) ≥1 impaired scores (i.e. ≤16th %ile) in ≥3 cognitive domains, using demographically-corrected normative data. (1) and (2) must include the Memory domain.

- The primary suspected etiology of amnestic MCI must be neurodegenerative, with competing differential diagnoses (e.g. psychiatric disorder, movement disorder, reversible causes, substance use) ruled out as the primary etiology/ies following a clinical evaluation by a healthcare provider.

- Ability to provide independent informed consent, consistent with the MCI diagnostic criterion of preserved independent function.

Exclusion Criteria:

- Dementia diagnosis per the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) or NIA-AA criteria.

- Anticholinergic, neuroleptic, or sedative use. Cholinesterase inhibitors, N-Methyl-D-aspartate (NMDA) receptor antagonists, and antidepressants are allowed if on a stable regimen of four weeks prior to enrollment.

- History of significant or unstable condition/s that may impact cognition such as significant cardiac, cerebrovascular, or metabolic disease, severe mental illness (e.g. bipolar disorder, psychoses), alcohol or substance use disorder, developmental disorder, or other neurologic disease (e.g. severe brain injury, seizures).

- MRI and TMS contraindications (e.g., implants, claustrophobia, conditions/treatments that lower seizure threshold, taking medications that have short half-lives, no quantifiable motor threshold, active substance use disorder, bipolar disorder).

Gender: All

Minimum Age: 65 Years

Maximum Age: 85 Years

Healthy Volunteers: No

Overall Official
Verification Date

September 2020

Responsible Party

Type: Principal Investigator

Investigator Affiliation: Medical University of South Carolina

Investigator Full Name: Andreana Benitez

Investigator Title: Assistant Professor

Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: High-dose accelerated rTMS

Type: Experimental

Acronym PUSH-Pilot
Patient Data No
Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov