Deep rTMS for Mild Neurocognitive Disorder in Older Adults

Official title

Feasibility and Tolerability of Deep Repetitive Transcranial Magnetic Stimulation for Mild Neurocognitive Disorder in Older Adults: A Pilot Study (DeepMIND)

Overview

This study aims to: (1) assess the feasibility and tolerability of three deep transcranial magnetic stimulation (dTMS) coils H1, H4, and H7 in older adults with mild neurocognitive disorder (mild NCD); and (2) evaluate changes in cognition through neuropsychological testing, brain activity through EEG, and mood and sleep through self-report questionnaires. Participants will be assigned to one of three arms: H1- coil vs. H4-coil vs. H7-coil, and all participants will complete assessments examining dTMS side effects, mental health symptoms, and cognition. EEG, questionnaires, and CNS vital signs will be measured at baseline, midpoint (after 10th session- before dTMS treatment on visit 11), and end point, as well as follow up. Collectively, the study will address the absolute and differential feasibility and tolerability of the H1, H4 and H7 coils to provide preliminary data for a future randomized controlled trial comparing this novel intervention to a sham stimulation (placebo) control.

Detailed description

Transcranial magnetic stimulation (TMS) is a non-invasive therapeutic technique used to stimulate regions of the brain using magnetic pulses. Repeated TMS delivers sequences of pulses for multiple days in a row and is an approved treatment for several psychiatric conditions. Deep TMS (dTMS) is a new technique that uses modified magnetic Hesed coils (H-coils) to stimulate deeper regions of the brain and has been FDA- and Health Canada-approved for major depressive disorder (MDD), obsessive-compulsive disorder, smoking cessation, and anxious-depression in adults. While some research has demonstrated potential benefits of dTMS for cognitive impairment in Alzheimer's disease and other neurodegenerative conditions, its feasibility and tolerability in mild neurocognitive disorder (mild NCD) remain largely unexplored. This innovative pilot study will examine the feasibility and tolerability (side effects, impacts on mental health and cognition), of three dTMS coils (H1, H4 and H7) in older adults with mild NCD. The H1-coil targets bilateral prefrontal cortices, the H4-coil targets the insula and prefrontal cortex, and the H7-coil targets the medial prefrontal cortex and anterior cingulate cortex. These regions are known to be involved in memory, attention, mood regulation, and executive functioning and implicated in mild NCD.

Using an open-label, parallel design, participants aged 60-90 will be assigned to one of three dTMS coils and will complete a six-week course of 20 stimulation sessions (five sessions per week for the first two weeks, three sessions per week for the next two, and two sessions per week for the final two weeks). Each session will include a brief cognitive "priming" task designed to engage brain regions prior to stimulation. In addition to monitoring side effects and retention rates, the study will measure participants' cognitive performance through neuropsychological testing and assess brain function changes through electroencephalogram (EEG) recordings. EEG will be conducted at baseline, midpoint (after 10th session- before dTMS treatment on visit 11), and end point, as well as follow up to capture changes in neural activity and connectivity. This study will lay critical groundwork for a larger, future randomized controlled trial.

Interventions

• Device Brainsway H1-Coil Deep TMS System
  Participants assigned to this arm will complete a 6-week course of 20 dTMS stimulation session using the Brainsway H1-coil.
• Device Brainsway H4-Coil Deep TMS System
  Participants assigned to this arm will complete a 6-week course of 20 dTMS stimulation session using the Brainsway H4-coil.
• Device Brainsway H7-Coil Deep TMS System
  Participants assigned to this arm will complete a 6-week course of 20 dTMS stimulation session using the Brainsway H7-coil.

Primary outcome measures

• Feasibility criteria 1: Protocol completion [Time frame: 6 weeks]
• Feasibility criteria 2: Retention rate [Time frame: 6 weeks]
• Feasibility criteria 3: Screening rates and capacity [Time frame: 6 weeks]
• Feasibility criteria 4: Recruitment rate and capacity [Time frame: 6 weeks]
• Feasibility criteria 5: Duration of intervention and assessment processes [Time frame: 6 weeks]
• Feasibility criteria 6: Safety of H-coil dTMS treatment [Time frame: 6 weeks]
• Tolerability of H-coil dTMS treatment [Time frame: 6 weeks]

Secondary outcome measures (12)

• Changes from baseline on the Everyday Memory Questionnaire (EMQ) [Time frame: 6 weeks + one-month follow-up]
• Changes from baseline in Neurocognitive Performance measured by the CNS Vital Signs Test Battery [Time frame: 6 weeks + one-month follow-up]
• Change from baseline on the Hamilton Depression Rating Scale- 24 item (HDRS-24). [Time frame: 6 weeks + one-month follow-up]
• Change from baseline on the General Anxiety Disorder- 7 item (GAD-7) [Time frame: 6 weeks + one-month follow-up]
• Change from baseline on the Pittsburgh Sleeping Quality Index (PSQI) [Time frame: 6 weeks + one-month follow-up]
• Change from baseline on the Patient Health Questionnaire (PHQ - Somatic Symptoms) [Time frame: 6 weeks + one-month follow-up]
• Changes from baseline on the Multifactorial Memory Questionnaire (MMQ) [Time frame: 6 weeks + one-month follow-up]
• Changes from baseline in resting-state EEG [Time frame: 6 weeks + one-month follow-up]
• Changes from baseline in WHO Quality of Life Questionnaire - BREF (WHOQOL-BREF) [Time frame: 6 weeks + one-month follow-up]
• Changes from baseline Patient Global Impression of Improvement (PGI-I) [Time frame: 6 weeks + one-month follow-up]
• Changes from baseline on the Monetary Choice Questionnaire (Delay Discounting) [Time frame: 6 weeks + one-month follow-up]
• Changes from baseline in blood biomarkers [Time frame: 6 weeks + one-month follow-up]

Eligibility criteria

Inclusion criteria

• 60 - 90 years old
• Able to provide informed consent to participate in the study
• Subjective concern of mild decline in cognitive function over the past year
• Mild impairment in cognitive performance
• Preserved independence in everyday activities
• Independently mobile (e.g., participants must be able to get in and out of a chair on their own)
• Participants will be required to be on stable dosages of other psychotropic medications for at least 4 weeks prior to screening

Exclusion criteria

• Currently receiving treatment or subjective need for treatment for bipolar I or II disorder; psychotic disorder
• Active suicidal behavior
• Severe depression and/or anxiety
• Other neurological or psychiatric disorders accounting for the cognitive deficits
• Impairment in basic and/or instrumental activities of daily living
• Substance use disorder (other than tobacco use disorder) in the past 3 months before entering the study
• Traditional contraindications to rTMS: Intracranial or metal implants in the head or nearby regions, excluding the mouth, that cannot be safely removed; History of epilepsy or seizures; Active unstable medical condition (recent laboratory and neuroimaging alterations, delirium); Pacemaker and/or implantable cardioverter-defibrillators; current use of bupropion, treatment with equivalent benzodiazepine dose to lorazepam >2 mg/day
• People with severe literacy, visual, or hearing issues that affect the ability to engage in the interviews
• People with recurring migraines or headaches (weekly or more)
• Frequent dizziness/vertigo
• Individuals residing beyond the borders of the Greater Hamilton Area and its neighbouring vicinities

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

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Other

Study locations

Canada · 1 center

• Peter Boris Centre for Addictions Research, St. Joseph's Healthcare Hamilton — Hamilton

Identifiers

NCT: NCT07038798 · 18440

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗