The Effects of Intermittent Theta Burst Stimulation in MCI and Early AD

Alzheimer Disease Clinical Trial

Official title:

Cognitive Effects of Theta Burst Stimulation in Mild Cognitive Impairment and Alzheimer's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04555941
• Other study ID #: N202003022
• Status: Completed
• Phase: Phase 2
• Start date: October 5, 2020
• Est. completion date: January 31, 2022

Study information

• Verified date: October 2022
• Source: Taipei Medical University Shuang Ho Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation technique that is increasingly used for a growing number of research and clinical applications.Typically, this transient magnetic field is focally applied with a figure-of-eight coil that is carefully placed on the surface of the scalp over a targeted stimulation site. Patterned repetitive TMS (rTMS), such as theta burst stimulation (TBS) can produce long-lasting effects on neural activity and behavior beyond the stimulation period (Chou et al., 2015a; Fitzgerald et al., 2006). In general, high frequency (> 5 Hz) rTMS and its newer version, intermittent theta burst stimulation (iTBS), facilitate cortical excitability, whereas low frequency (about 1 Hz) rTMS and continuous theta burst stimulation contribute to opposite effects (Pascual-Leone et al., 2000; Huang et al., 2005; Wassermann and Zimmermann, 2012).Careful manipulation of the parameters comprising these patterned rTMS pulse trains can induce neuroplastic changes that resemble either long-term potentiation (LTP) or depression (Chen et al., 1997; Pascual-Leone et al., 1994). Early studies targeting the motor cortex helped elucidate which rTMS parameters promote particular responses and their neurophysiological underpinnings (Klomjai et al., 2015).

In recent years, rTMS has been closely investigated to evaluate its potential to modulate cognitive functions in Alzheimer'sdisease (AD) and mild cognitive impairment (MCI). As compared to conventional excitatory rTMS protocols, iTBS leads to comparable effects with similar number of pulses but considerable shorter duration and lower intensity of stimulation (Bakker et al., 2015; Rossi, Hallett, Rossini, Pascual-Leone, & Safety, 2009). Recent literature also suggest that TBS has lower rates of reported adverse event (AE) compared to rTMS (Najib & Horvath, 2014). Therefore, iTBS is assumed to modulate cognitive function in people with cognitive impairments.

Description:

Visit 1: Informed Consent, Brain MRI/Neuropsychological Battery

Visit 2-11: (up to a week after visit 1) iTBS - or Sham-Treatment (10 sessions, 80% Resting Motor Threshold, 2s stimulation 8s inter-stimulus interval per train, 20 trains per block, 3 blocks per session with a 5-min break, 1 session per day)

Visit 12: (1 day or same day after visit 11) Functional Brain MRI/Neuropsychological Battery

Visit 13: (4 weeks after visit 11) Functional Brain MRI/Neuropsychological Battery

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: January 31, 2022
• Est. primary completion date: January 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

Inclusion Criteria:

• normal visual acuity

• diagnosed with mild cognitive impairment or early dementia due to Alzheimer's disease (CDR = 0.5) by neurologists

Exclusion Criteria:

• (family) history of seizure attacks

• in intensive care

• history of drug/alcohol dependence

• assistants or students of the PI

• major systemic diseases concerning cognitive decline (e.g., cardiopulmonary failure, liver/renal failure, poor controlled DM, traumatic brain injury, stroke, or other neurodegenerative diseases)

• claustrophobia

• metal implants

• taking medication lowering the threshold of seizure attacks

• fear of using TMS

• with specific allergens

• pregnant or breastfeeding women

Related Conditions & MeSH terms

• Alzheimer Disease
• Cognitive Decline
• Cognitive Dysfunction
• Mild Cognitive Impairment

Intervention

Device:
• intermittent theta burst stimulation
active or Sham iTBS will be given to the AD/MCI patient

Locations

Country	Name	City	State
Taiwan	Shuang Ho Hospital	New Taipei City

Sponsors (1)

Lead Sponsor	Collaborator
Taipei Medical University Shuang Ho Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes from baseline in scores of any tests of the Neuropsychological Battery	WAIS-IV short-form, Word Sequence Learning Test, Benton Visual Retention Test, Color Trial Tests, 3-D Dimensional Constructional Test, Visual Confrontation Naming, Semantic Verbal Fluency Test, Stroop Color-Word Test	Baseline, immediate post-iTBS, follow-up (4 weeks post-iTBS)
Secondary	Brain MRI	Change in white matter and brain activities at resting state at baseline compared to after iTBS stimulation	Baseline, immediate post-iTBS, follow-up (4 weeks post-iTBS)