Clinical trial NCT05440110: Cognitive Effects of Theta-burst Stimulation (TBS) in Suspected Non-Alzheimer Disease Pathophysiology (SNAP)
Official title: Cognitive Effects and Potential Mechanisms of Theta-burst Stimulation (TBS) in Suspected Non-Alzheimer Disease Pathophysiology (SNAP): a Pilot Study
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Suspected Non-Alzheimer Disease Pathophysiology (SNAP)
Keywords: Suspected Non-Alzheimer Disease Pathophysiology (SNAP)
theta-burst stimulation
repetitive transcranial magnetic stimulation (rTMS)
Lead sponsor: Chang Gung Memorial Hospital
Sponsor class: OTHER
First posted: 2022-06-30
Enrollment: 20
Sex: ALL
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a prospective, randomized controlled clinical trial for the first two weeks, followed by an open-label trial for the next two weeks, and combined functional neuroimaging study of 18F-FDG-PET to further explore the potential mechanisms. A total of 20 SNAP dementia patients will be recruited for consecutive two years, and be subjected to iTBS for 5 daily interventions per week for four consecutive weeks. Cognitive evaluation will be performed before and immediately after TBS intervention, and 8 weeks after TBS. Data on functional neuroimaging will be also collected before and after TBS protocol.
Primary purpose: TREATMENT

Brief summary: This is a pilot study to identify a homogeneous cohort of pathologically specific dementia with SNAP for clinical trial of brain stimulation.

Detailed description: The investigators apply the NIA-AA criteria to identify the individuals of biomarker-defined SNAP endophenotype. This is a prospective, randomized controlled clinical trial for the first two weeks, followed by an open-label trial for the next two weeks, and combined functional neuroimaging study of 18F-FDG-PET to further explore the potential mechanisms. A total of 20 SNAP dementia patients will be recruited for consecutive two years, and be subjected to iTBS for 5 daily interventions per week for four consecutive weeks. Cognitive evaluation will be performed before and immediately after TBS intervention, and 8 weeks after TBS. Data on functional neuroimaging will be also collected before and after TBS protocol.

Eligibility criteria: Inclusion Criteria:

1. Subjects aged 50-90 year.
2. Patients meet NIA-AA research criteria for suspected non-Alzheimer disease pathophysiology (SNAP) (Petersen, Smith et al. 1999; Jack, Bennett et al. 2018), and DSM-5 criteria for major neurocognitive disorder of dementia (Regier, Narrow et al. 2013).
3. Amyloid PET should ever be performed.
4. The CDR of subjects can be 0.5-2.

Exclusion Criteria:

1. Any subject has a definite diagnosis of epilepsy or history of seizure attack.
2. Current or past history of clinically significant neurological insults affecting brain structure or function like completed stroke, head injury or brain tumor. (cerebrovascular disorders, hydrocephalus and intra-cranial mass, documented by MRI; a history of traumatic brain injury or another neurological disease).
3. Any subject has clinically significant or unstable medical diseases including metabolic, renal, liver, lung or cardiovascular disorders including metabolic, renal, liver, lung or cardiovascular disorders.
4. Any subject has current alcohol or other substances abuse and/ or dependence within the recent one year, or prolonged history of major psychiatric disorder like schizophrenia, bipolar disorder, and previously prolonged substances abuse.
5. Any females who is pregnant or lactating.
6. General MRI, TMS and/or PET exclusion criteria including subjects who had received brain aneurysm surgery, or implanted pacemaker, mechanical valves, cochlear implant or other metal devices/ objects that are not MR compatible in the body.

Withdrawal criteria

1. Complications onset after intervention that affect efficacy and safety judgments.
2. New onset or progression of disease that may affect outcomes.
3. Use of other therapies or drugs during the intervention period to change cognitive functions.
4. Any subjects who are recognized as high risk of adverse effects by principle investigator.

Primary outcomes:
measure: The changes of Mini-Mental State Examination (MMSE) total scores
timeFrame: baseline (T0) and immediately after 2 weeks of TBS (T2), and 4 weeks of TBS (T4), and 8-week follow-up after TBS (T12)
measure: The changes of Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) total scores
timeFrame: baseline (T0) and immediately after 2 weeks of TBS (T2), and 4 weeks of TBS (T4), and 8-week follow-up after TBS (T12)
Secondary outcomes:
measure: The standard uptake values changes of FDG-PET
timeFrame: baseline (T0) and immediately after 2 weeks of TBS (T2), and 4 weeks of TBS (T4)
Other outcomes:
Locations:
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital
state: Guishan
Study officials:
affiliation: Chang Gung Memorial Hospital
name: KUAN YI WU
role: PRINCIPAL_INVESTIGATOR
References: