Brain Stimulation and Cognitive Training for MCI

Official title

Combining Brain Stimulation With Computerized Cognitive Training for MCI

Overview

This is a randomized clinical trial of a treatment that combines non-invasive brain stimulation with computerized cognitive training (CCT) for people with mild cognitive impairment (MCI). The form of brain stimulation used in this study is accelerated intermittent theta burst stimulation (iTBS). All participants receive the same amount of iTBS and are randomly assigned to engage in one of two types of CCT. The goals of the study are to see if this combined treatment is feasible and acceptable to people with MCI and whether combined iTBS and CCT improves memory, thinking skills, mood, and daily function.

Detailed description

This is a randomized, sham-controlled trial of combined intermittent theta burst stimulation (iTBS) and computerized cognitive training (CCT) for people with mild cognitive impairment (MCI). The primary objectives of this study are to determine the feasibility, acceptability, and preliminary effect sizes of 3-day combined iTBS+CCT for improving neurocognitive and psychosocial function in MCI.

Interventions

• Device Accelerated iTBS
  A MagVenture MagPro Transcranial Magnetic Stimulation (TMS) System with Brainsight neuronavigation will be used. All participants will receive active treatment: 12 sessions (3 min each) of iTBS on each of 3 treatment days within an 8-day span. A single session = 600 pulses of 50 Hz iTBS triplets delivered every 200ms in 2s trains repeated every 10s (8s inter-train interval) for 190s. Stimulation intensity is 120% resting motor threshold (rMT) delivered at the left dorsolateral prefrontal cortex.
• Device Computerized Cognitive Training
  CCT will be delivered through the online BrainHQ platform. Participants will engage in adaptive visual speed of processing training during the 15-min breaks between iTBS sessions (11 sessions on each treatment day, total CCT time = 495 min).
• Device Sham Computerized Cognitive Training
  Sham CCT will be delivered through the online BrainHQ platform. Participants will engage in non-adaptive control games during the 15-min breaks between iTBS sessions (11 sessions on each treatment day, total sham CCT time = 495 min).

Primary outcome measures

• Retention [Time frame: From enrollment to the end of study at week 6 (1-month post-treatment assessment).]
• Adherence [Time frame: On each of the 3 treatment days during Week 1]
• Acceptability [Time frame: Week 0 (1 week pre-treatment), Week 2 (1 week post-treatment)]
• Change in NIH Toolbox-Cognition Battery (NIHTB-CB) Fluid Composite [Time frame: Week 0 (1 week pre-treatment), Week 2 (1 week post-treatment), and Week 6 (4 weeks post-treatment)]
• Change in Preclinical Alzheimer's Cognitive Composite (Mayo-PACC) Z-score [Time frame: Week 0 (1 week pre-treatment), Week 2 (1 week post-treatment), and Week 6 (4 weeks post-treatment)]

Secondary outcome measures (2)

• Change in Quick Dementia Rating System (QDRS) Total Score [Time frame: Week 0 (1 week pre-treatment), Week 2 (1 week post-treatment), and Week 6 (4 weeks post-treatment)]
• Change in Informant-rated Everyday Cognition (ECog-II) Scale Total Score [Time frame: Week 0 (1 week pre-treatment), Week 2 (1 week post-treatment), and Week 6 (4 weeks post-treatment)]

Eligibility criteria

Inclusion criteria

• Age 60-85 (inclusive).
• English as a first/primary language.
• Adequate sensorimotor function and verbal expressive abilities to complete all assessments.
• 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.
• Meets the following requirements for current and prior medications and treatments:

• Is on fixed pharmacotherapy (i.e. stable dose of medication/s) for ≥ 4 weeks before enrollment. This includes, but is not limited to, cholinesterase inhibitors, NMDA receptor antagonists, and antidepressants.
• Anti-amyloid monoclonal antibody therapy for AD/MCI:

• Prior treatment is permitted if last infusion occurred ≥ 8 weeks before enrollment.
• Current treatment is permitted if the dose has been stable for ≥ 12 weeks before enrollment, with no planned dose change during study participation.
• Prior TMS treatment is permitted if the last stimulation session was ≥ 24 weeks before enrollment.
• Documented diagnosis of MCI per NIA-AA criteria or Mild Neurocognitive Disorder per DSM-5 criteria by a healthcare provider within the past year, with a presumed etiology of possible or probable AD 7. Met actuarial neuropsychological criteria for MCI43 within the past year (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).

Exclusion criteria

• Telephone Interview for Cognitive Status (TICS) score of ≤ 22 suggestive of dementia.
• Prior diagnosis of Dementia (NIA-AA) or Major Neurocognitive Disorder (DSM-5).
• Daily/weekly anticholinergic or sedative use. Stimulants may be allowed pending investigator review.
• 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), severe mental illness (e.g., bipolar disorder, psychoses), alcohol or substance use disorder, 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).
• Plan to initiate treatment for AD/MCI with monoclonal antibody therapy during study participation.
• For those currently receiving monoclonal antibody therapy, documented history of clinically significant amyloid-related imaging abnormalities (ARIA) in their medical record.
• Current use of any implanted brain stimulation device.
• Enrolled in a clinical trial or has received an investigational medication or device in the last 30 days that may impact cognition or mood.
• MRI contraindications (e.g., ferromagnetic implants, claustrophobia).
• Unable or unwilling to engage in BrainHQ activities.
• TMS contraindications (e.g., ferromagnetic implants, conditions or treatments that lower seizure threshold, taking medications that have short half-lives) or no identifiable motor threshold.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

United States · 1 center

• Medical University of South Carolina — Charleston

Identifiers

NCT: NCT07526740 · Pro00138352 · 1K23AG090691-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗