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Theta-burst Stimulation on Cognitive Function in the Patients With Young-onset Alzheimer's Disease Dementia

Primary Purpose

Alzheimer Disease, Early Onset

Status

Enrolling by invitation

Phase

Not Applicable

Locations

Taiwan

Study Type

Interventional

Intervention

Theta-burst stimulation (TBS)

About this trial

This is an interventional treatment trial for Alzheimer Disease, Early Onset focused on measuring Young-onset dementia, Alzheimer's disease, rTMS, TBS

Eligibility Criteria

50 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Any patient has a definite diagnosis of AD dementia according to the NIA-AA criteria for intermediate-to-high levels of biological evidence of probable and possible AD dementia (McKhann et al. 2011).
Dementia onset before age 65 years old.
Age between 50-75 years old for patient and control group.
The severity of dementia is limited to mild to moderate stage in current project. The definition of mild to moderate stage of dementia is based on the clinical dementia rating scale (CDR) from 0.5-2.
Cognitively normal controls MMSE≧24, CDR should be 0.
Informed consent provided by the patient and family.

Exclusion Criteria:

Any subject has a definite diagnosis of epilepsy or history of seizure attack.
Current or past history of clinically significant neurological insults affecting brain structure or function like completed stroke, head injury or brain tumor.
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
Any subject has current alcohol or other substances abuse and/ or dependence within the recent one year, or previously prolonged history of substances abuse
Any females who is pregnant or lactating
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 magnetic resonance (MR) compatible in the body.
Any subject has allergic reaction to 18F-florbetapir or 18F-FDG radiotracers.

Sites / Locations

Chang Gung Memorial Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Sham Comparator

No Intervention

Arm Label

Active group

Sham group

Cognitively normal control

Arm Description

Active group will receive active stimulation of standard intermittent TBS (iTBS) protocol.

Sham group will receive sham stimulation of the same iTBS protocol with the coil set at 90 to the skull.

Cognitively normal controls will be recruited for neuroimaging comparison.

Outcomes

Primary Outcome Measures

Change from baseline MMSE total scores immediately after TBS intervention

The changes of Mini-Mental State Examination (MMSE) total scores (score range from 0 to 30, higher values represent a better cognitive outcome)

Change from baseline MMSE total scores 4 weeks after TBS intervention

The changes of Mini-Mental State Examination (MMSE) total scores (score range from 0 to 30, higher values represent a better cognitive outcome)

Change from baseline ADAS-Cog total scores immediately after TBS intervention

The changes of Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) total scores (score range from 0 to 70, higher score indicates a worse cognitive outcome)

Change from baseline ADAS-Cog total scores 4 weeks after TBS intervention

The changes of Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) total scores (score range from 0 to 70, higher score indicates a worse cognitive outcome)

Secondary Outcome Measures

The standard uptake values changes of FDG-PET

The standard uptake values (SUV) changes of cerebral glucose metabolism using 18F-FDG-PET

Full Information

NCT ID

NCT04042532

First Posted

July 28, 2019

Last Updated

August 14, 2023

Sponsor

Chang Gung Memorial Hospital

1. Study Identification

Unique Protocol Identification Number

NCT04042532

Brief Title

Theta-burst Stimulation on Cognitive Function in the Patients With Young-onset Alzheimer's Disease Dementia

Official Title

The Effects and Mechanisms of Theta-burst Stimulation on Cognitive Function in the Patients With Biomarker-defined Young-onset Alzheimer's Disease Dementia

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Enrolling by invitation

Study Start Date

January 3, 2020 (Actual)

Primary Completion Date

July 31, 2024 (Anticipated)

Study Completion Date

July 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Chang Gung Memorial Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

Young-onset dementia (YOD) is a devastating condition, and it produces substantial psychosocial impacts on individual's functioning and family's care burden. Alzheimer's disease (AD) dementia is the most common type in YOD. Medication treatment Response was limited and unsatisfactory. In recent years, repetitive transcranial magnetic stimulation (rTMS) has been considered an alternative for the improvement of cognition in older patients with cognitive impairment. This study aims to examine the effects and potential mechanisms of theta-burst stimulation (TBS) on cognitive function in individuals with young-onset AD.

Detailed Description

The investigators apply the National Institute on Aging-Alzheimer's Association (NIA-AA) criteria to recruit the biomarker-defined, young-onset AD patients with intermediate-to-high levels of biological evidence. This is a randomized, sham-controlled, 2-way crossover study, and combined neuroimaging study of 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) to further explore the potential mechanisms. This study will consist of two intervention periods. A total of 50 young-onset AD patients will be consecutively recruited and be randomized into one of two groups: active and sham stimulation (n = 25 per group) in every intervention period. Besides, 20 cognitively normal subjects will be recruited for neuroimaging comparison. Cognitive evaluation will be performed before and immediately after treatment at 2 weeks of TBS intervention, and 4 weeks after TBS. Data on functional neuroimaging will be also collected before and after TBS protocol.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Alzheimer Disease, Early Onset

Keywords

Young-onset dementia, Alzheimer's disease, rTMS, TBS

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Masking

ParticipantOutcomes Assessor

Allocation

Randomized

Enrollment

70 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Active group

Arm Type

Active Comparator

Arm Description

Active group will receive active stimulation of standard intermittent TBS (iTBS) protocol.

Arm Title

Sham group

Arm Type

Sham Comparator

Arm Description

Sham group will receive sham stimulation of the same iTBS protocol with the coil set at 90 to the skull.

Arm Title

Cognitively normal control

Arm Type

No Intervention

Arm Description

Cognitively normal controls will be recruited for neuroimaging comparison.

Intervention Type

Device

Intervention Name(s)

Theta-burst stimulation (TBS)

Intervention Description

We will perform standard intermittent TBS (iTBS) parameters to left DLPFC of every patient in the study. The frequency parameters of TBS are 3-pulse 50-Hz bursts, every 200 ms at 5 Hz, and the intensity is 90% of active motor threshold. A single session of iTBS contains 2 s of TBS repeated every 10 s for 20 times. In this study, we will give two sessions of iTBS separated by 15 min.

Primary Outcome Measure Information:

Title

Change from baseline MMSE total scores immediately after TBS intervention

Description

The changes of Mini-Mental State Examination (MMSE) total scores (score range from 0 to 30, higher values represent a better cognitive outcome)

Time Frame

Before and immediately after TBS intervention

Title

Change from baseline MMSE total scores 4 weeks after TBS intervention

Description

The changes of Mini-Mental State Examination (MMSE) total scores (score range from 0 to 30, higher values represent a better cognitive outcome)

Time Frame

Before and 4 weeks after TBS intervention

Title

Change from baseline ADAS-Cog total scores immediately after TBS intervention

Description

The changes of Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) total scores (score range from 0 to 70, higher score indicates a worse cognitive outcome)

Time Frame

Before and immediately after TBS intervention

Title

Change from baseline ADAS-Cog total scores 4 weeks after TBS intervention

Description

The changes of Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) total scores (score range from 0 to 70, higher score indicates a worse cognitive outcome)

Time Frame

Before and 4 weeks after TBS intervention

Secondary Outcome Measure Information:

Title

The standard uptake values changes of FDG-PET

Description

The standard uptake values (SUV) changes of cerebral glucose metabolism using 18F-FDG-PET

Time Frame

Before and 1 week after TBS intervention

10. Eligibility

Sex

All

Minimum Age & Unit of Time

50 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Any patient has a definite diagnosis of AD dementia according to the NIA-AA criteria for intermediate-to-high levels of biological evidence of probable and possible AD dementia (McKhann et al. 2011). Dementia onset before age 65 years old. Age between 50-75 years old for patient and control group. The severity of dementia is limited to mild to moderate stage in current project. The definition of mild to moderate stage of dementia is based on the clinical dementia rating scale (CDR) from 0.5-2. Cognitively normal controls MMSE≧24, CDR should be 0. Informed consent provided by the patient and family. Exclusion Criteria: Any subject has a definite diagnosis of epilepsy or history of seizure attack. Current or past history of clinically significant neurological insults affecting brain structure or function like completed stroke, head injury or brain tumor. 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 Any subject has current alcohol or other substances abuse and/ or dependence within the recent one year, or previously prolonged history of substances abuse Any females who is pregnant or lactating 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 magnetic resonance (MR) compatible in the body. Any subject has allergic reaction to 18F-florbetapir or 18F-FDG radiotracers.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

KUAN YI WU

Organizational Affiliation

Chang Gung Memorial Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Chang Gung Memorial Hospital

City

Taoyuan

State/Province

Guishan

ZIP/Postal Code

333

Country

Taiwan

12. IPD Sharing Statement

Plan to Share IPD

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Theta-burst Stimulation on Cognitive Function in the Patients With Young-onset Alzheimer's Disease Dementia

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