iTBS rTMS in Mild Cognitive Impairment

Maria I. Lapid, M.D.

Status: Enrolling

Conditions: Mild Cognitive Impairment

Treatments: Device: iTBS rTMS

Study type: Interventional

Funder types: Other

Identifiers

NCT05327257

21-010661

Details and patient eligibility

About

The purposes of this research are to test whether it is feasible to administer a treatment protocol called intermittent theta burst stimulation (iTBS) repetitive transcranial magnetic stimulation (rTMS) in adults with mild cognitive impairment (MCI), and to test whether iTBS rTMS treatments can improve memory in mild cognitive impairment (MCI).

Full description

To test the feasibility of conducting a 10-day Intermittent Theta Burst Stimulation (iTBS) repetitive Transcranial Magnetic Stimulation (rTMS) protocol twice using a cross-over design in individuals with Mild Cognitive Impairment (MCI), pilot test the study protocol to assess study design, and collect pilot data on the effect of stimulations over 3 different brain regions (left dorsolateral prefrontal cortex (DLPFC), lateral parietal cortex (LPC), vertex) on working memory, new-learning and executive function in MCI. Neuropsychological and sleep measures, functional brain magnetic resonance imaging (fMRI), high density EEG and questionnaires will be performed at 5 timepoints - baseline, post-treatment after first period of 10 daily iTBS rTMS sessions, post-washout period of 4 weeks, post-treatment after cross-over to second period of 10 daily iTBS rTMS sessions, and 4 weeks follow-up post-treatment.

Enrollment: 25 estimated patients

Sex: All

Ages: 55 to 90 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

• Must speak English fluently

• Diagnosis of MCI as defined by:

  • Clinical diagnosis by a neurologist
  • Neuropsychological testing support of MCI
  • Meet criteria for MCI
  • Subjective cognitive decline reported by participant and/or an informant
  • Objective memory impairment in one or more cognitive domains for age
  • Essentially preserved general cognitive function
  • Largely intact functional activities
  • Does not meet criteria for dementia as judged by a clinician

• Eligible for transcranial magnetic stimulation (TMS) based on safety criteria

• Clinical Dementia Rating=0.5

• Geriatric Depression Scale score less than 6

• Medically stable and in good general health

• Not pregnant, lactating, or of childbearing potential

• Stable medication regimen for at least 4 weeks prior to baseline visit

• Adequate visual and auditory abilities to complete neuropsychological testing

• Ability to provide informed consent

• Have a care partner who is available to accompany the participant to study visits for the duration of the protocol.

Exclusion Criteria

• Inability to communicate in the English language

• Meet criteria for dementia

• Contraindications to TMS or MRI, including patients who have

  • conductive, ferromagnetic or other magnetic-sensitive metals implanted in their head or within 30 cm of the treatment coil (e.g., cochlear implants, implanted electrodes/stimulators, aneurysm clips or coils, stents, bullet fragments or jewelry)
  • active or inactive implants, including deep brain stimulators, cochlear implants, vagus nerve stimulators or implanted device leads

• Any true positive findings on the TMS safety screening form

• Prior exposure to TMS, electroconvulsive therapy (ECT), or any neurostimulation within the past 12 months

• History of epilepsy or seizures

• Medical conditions that increase risk of seizures

  • History of traumatic brain injury
  • History of intracranial mass or lesion
  • History of stroke, including hemorrhagic stroke and ischemic stroke

• Psychiatric disorders

  • Primary psychotic disorder (schizophrenia, schizoaffective, or schizophreniform disorder), any history
  • Primary mood disorder (major depressive disorder, bipolar disorder) within the past 12 months
  • Substance use disorder (except caffeine and nicotine) within the past 12 months

• Active symptoms of depression, anxiety, mania, psychosis, or substance use (except caffeine and nicotine) within the past year

  • Active symptoms of depression will be identified based on geriatric depression scale ≥ 6
  • Other active symptoms of psychiatric conditions to be determined by study investigators

• Sleep disorders that are considered clinically significant and not sufficiently treated by the investigative team, including untreated obstructive sleep apnea (apnea-hypopnea index >15), untreated/suboptimally treated REM sleep behavior disorder, untreated/suboptimally treated restless legs syndrome

• Pregnancy or suspected pregnancy

• Participation in another concurrent interventional clinical trial

• Any unstable medical condition

• Inability to provide informed consent

• Inability to adhere to the protocol

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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25 participants in 5 patient groups

iTBS rTMS Left Dorsolateral Prefrontal Cortex (DLPFC) then Vertex

Experimental group

Description:

Subjects will receive 10 consecutive days of daily single session of iTBS rTMS for 3.5 minutes per day over the DLPFC in the first treatment period, complete a washout period of 4 weeks then receive 1 session of iTBS rTMS for 3.5 minutes daily over the vertex for 10 consecutive days.

Treatment:

Device: iTBS rTMS

iTBS rTMS Lateral Parietal Cortex (LPC) then Vertex

Experimental group

Description:

Subjects will receive 10 consecutive days of daily single session of iTBS rTMS for 3.5 minutes per day over the LPC in the first treatment period, complete a washout period of 4 weeks then receive 1 session of iTBS rTMS for 3.5 minutes daily over the vertex for 10 consecutive days.

Treatment:

Device: iTBS rTMS

iTBS rTMS Vertex then Left Dorsolateral Prefrontal Cortex (DLPFC)

Experimental group

Description:

Subjects will receive 1 session of iTBS rTMS for 3.5 minutes daily over the vertex for 10 consecutive days in the first treatment period, complete a washout period of 4 weeks then receive 10 consecutive days of daily single session of iTBS rTMS for 3.5 minutes per day over the DLPFC.

Treatment:

Device: iTBS rTMS

iTBS rTMS Vertex then Lateral Parietal Cortex (LPC)

Experimental group

Description:

Subjects will receive 1 session of iTBS rTMS for 3.5 minutes daily over the vertex for 10 consecutive days in the first treatment period, complete a washout period of 4 weeks then receive 10 consecutive days of daily single session of iTBS rTMS for 3.5 minutes per day over the LPC.

Treatment:

Device: iTBS rTMS

iTBS rTMS Vertex only

Sham Comparator group

Description:

Cognitively normal and healthy controls will receive 1 session of iTBS rTMS for 3.5 minutes daily over the vertex for 10 consecutive days. The vertex serves as a control as there are no functional improvements in cognition with stimulation of the vertex region.

Treatment:

Device: iTBS rTMS