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

NCT04503096 | Completed Results DMC FDA Device

• 1 other identifier: Pro00100536
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Mild Cognitive Impairment

Outcome Measures

Primary Outcomes (5)

• Number of Participants With Clinically Significant Structural Brain Change on T1- and T2-weighted Magnetic Resonance Imaging (MRI)

  Clinically significant structural brain change were determined by a board-certified neuroradiologist who reviewed both the pre-treatment and post-treatment structural (T1- and T2-weighted) MRI scans to identify the presence of any changes from pre- to post-treatment based on their clinical read of the images.

  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)

  The MoCA is a psychometrist-administered brief cognitive assessment tool with raw total scores ranging from 0 to 30, with higher values indicating better cognition. For this analysis raw total scores were converted to age- and education-adjusted Z-scores using published norms (Rossetti et al., 2011). Z-scores have a mean of 0 and a standard deviation of 1. Lower scores indicate worse performance. The outcome measure reported below is the mean Z-score score at the 1-week post-treatment assessment. The statistical analysis compares this mean score to the mean score at Baseline.

  Baseline prior to treatment and at follow-up within 1 week post-treatment

• Change in the Review of Systems Criteria Compared to Baseline

  A review of systems questionnaire will be administered to rate the subjective symptom (headache, scalp pain, arm/hand pain, other pain(s), numbness/tingling, other sensation(s), weakness, loss of dexterity, vision/hearing change(s), ear ringing, nausea/vomiting, appetite loss, rash, skin change(s) or any other symptom(s)) on a scale of 0 to 5 (none, minimal, mild, moderate, marked, severe).

  Baseline prior to treatment and at follow-up within 1 week post-treatment

• Patient Perception of Treatment Acceptability

  A 15-item study-specific questionnaire of rTMS treatment acceptability, with each item rated on a scale from 1 to 5 (1 = not at all, 3 = somewhat, 5 = very much so). Higher scores indicate better acceptability for the first 10 items, lower scores indicate better acceptability for the last 5 items.

  Administered at post-treatment

• Retention Rate

  Percentage of participants who completed the study (n=21) relative to all participants who initiated treatment (n=22).

  Baseline prior to treatment and at follow-up within 1 week post-treatment

Secondary Outcomes (3)

• 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

• Change From Baseline Cognition, as Measured by the Fluid Cognition Composite Score From the NIH Toolbox Cognition Battery

  Baseline prior to treatment and at follow-up within 1 week post-treatment

Study Arms (1)

High-dose accelerated rTMS

EXPERIMENTAL

Device: High-dose accelerated rTMS

Interventions

High-dose accelerated rTMS DEVICE

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% resting motor threshold (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.

High-dose accelerated rTMS

Eligibility Criteria

• Age: 65 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Age 60-85
• 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.

You may not qualify if:

• Dementia diagnosis per the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) or NIA-AA criteria.
• Daily/weekly use of anticholinergics, neuroleptics, sedatives, or bupropion. Stimulant use may be allowed pending investigator review. Cholinesterase inhibitors, 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).
• Is enrolled in a clinical trial and/or has received an investigational medication within the last 30 days.

Sponsors & Collaborators

• Medical University of South Carolina: lead
• National Center of Neuromodulation for Rehabilitation: collaborator

Study Sites (1)

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Related Publications (1)

• Aghamoosa S, Lopez J, Rbeiz K, Fleischmann HH, Horn O, Madden K, Caulfield KA, Antonucci MU, Revuelta G, McTeague LM, Benitez A. A phase I trial of accelerated intermittent theta burst rTMS for amnestic MCI. J Neurol Neurosurg Psychiatry. 2024 Oct 16;95(11):1036-1045. doi: 10.1136/jnnp-2023-332680.

  PMID: 38719432 DERIVED

MeSH Terms

Conditions

Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Andreana Benitez PhD
• Organization: Medical University of South Carolina

benitez@musc.edu

(843) 876-8479

Study Officials

• Andreana Benitez, PhD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

• Lisa McTeague, PhD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: August 3, 2020
• First Posted: August 7, 2020
• Study Start: April 12, 2021
• Primary Completion: June 29, 2022
• Study Completion: July 27, 2022
• Last Updated: September 7, 2023
• Results First Posted: July 19, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)