Transcranial Magnetic Stimulation for MCI

NCT05992831 | Recruiting DMC FDA Device

• 2 other identifiers: Pro00127160R01AG081237
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mild Cognitive Impairment; Depression

Keywords

"mild cognitive impairment", Depression

Outcome Measures

Primary Outcomes (2)

• Change in Geriatric Depression Scale (GDS) raw score

  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.

  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)

• Change in NIH Toolbox-Cognition Battery (NIHTB-CB) Fluid Composite

  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.

  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)

Secondary Outcomes (3)

• Change in PROMIS Depression T-score

  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)

• Change in Alzheimer's Disease Cooperative Study scale for Activities of Daily Living in MCI (ADCS-ADL-MCI)

  Week 0 (1 week pre-treatment) Week 10 (8 weeks post-treatment), and Week 26 (6 months post-treatment)

• Change in Clinical Dementia Rating (CDR) scale Sum of Boxes

  Week 0 (1 week pre-treatment) Week 10 (8 weeks post-treatment), and Week 26 (6 months post-treatment)

Other Outcomes (4)

• Change in PROMIS (Anxiety, Sleep Disturbance, Fatigue, and General Life Satisfaction)

  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)

• Change in NIH Toolbox-Emotion Battery (NIHTB-EB) T-scores

  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)

• Change in Dimensional Apathy Scale (DAS) raw scores

  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)

Study Arms (6)

Dose Step 1 - 0 Active Accelerated iTBS Sessions

SHAM COMPARATOR

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

Device: Sham Comparator

Dose Step 2 - 12 Active Accelerated iTBS Sessions

EXPERIMENTAL

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).

Device: Accelerated iTBS; Device: Sham Comparator

Dose Step 3 - 24 Active Accelerated iTBS Sessions

EXPERIMENTAL

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).

Device: Accelerated iTBS; Device: Sham Comparator

Dose Step 4 - 36 Active Accelerated iTBS Sessions

EXPERIMENTAL

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).

Device: Accelerated iTBS; Device: Sham Comparator

Dose Step 5 - 48 Active Accelerated iTBS Sessions

EXPERIMENTAL

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).

Device: Accelerated iTBS; Device: Sham Comparator

Dose Step 6 - 60 Active Accelerated iTBS Sessions

EXPERIMENTAL

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).

Device: Accelerated iTBS

Interventions

Accelerated iTBS DEVICE

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.

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

Sham Comparator DEVICE

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.

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

Eligibility Criteria

• Age: 60 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Medical University of South Carolina: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

RECRUITING

MeSH Terms

Conditions

Cognitive Dysfunction; Depression

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Study Officials

• Andreana Benitez, PhD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

• Lisa McTeague

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andreana Benitez, PhD

CONTACT

843-876-2479; benitez@musc.edu

Katrina Madden, MBA

CONTACT

843-792-9186; maddenka@musc.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Each participant will be randomized to one of six possible dose-steps for the duration of the 6 treatment days (of their choosing) within a span of 2 weeks.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor-Faculty

Model Details: Each participant will be randomized to one of six possible dose-steps for the duration of the 6 treatment days (of their choosing) within a span of 2 weeks. We will use the FDA-approved MagVenture MagPro TMS System. Total treatment time will be controlled; all participants will perceive receiving treatment for 10 3-min stimulation sessions with 10-15 min inter-session intervals, resulting in a 2-3 hour treatment day. In addition to block randomization to dose step (which determines how many total active sessions they receive), the order of daily active and/or sham sessions will also be randomized. For example, if a participant is assigned to receive 4 active sessions in a day, 6 sham sessions will be given at random. 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.

Study Record Dates

• First Submitted: July 31, 2023
• First Posted: August 15, 2023
• Study Start: June 18, 2024
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): April 30, 2028
• Last Updated: April 2, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: starting 6 months after publication

Locations

US (1)