Alzheimer Disease, Early OnsetNCT04042532
Theta-burst Stimulation on Cognitive Function in the Patients With Young-onset Alzheimer's Disease Dementia
A study testing Theta-burst stimulation (TBS) in people with Alzheimer Disease, Early Onset, run by Chang Gung Memorial Hospital at 1 site in Taiwan.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer Disease, Early Onset
- What is being tested?
- Theta-burst stimulation (TBS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteTaiwan
- Study dates
- 3 Jan 2020to 30 Jun 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Alzheimer Disease, Early Onset
- Being tested
- Theta-burst stimulation (TBS)
- Keywords
- Young-onset dementia, Alzheimer's disease, rTMS, TBS
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Theta-burst stimulation (TBS)Device
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.
| Study group | Role | What they receive |
|---|---|---|
| Active group | Active comparator | Active group will receive active stimulation of standard intermittent TBS (iTBS) protocol. Receives: Device: Theta-burst stimulation (TBS) |
| Sham group | Sham comparator | Sham group will receive sham stimulation of the same iTBS protocol with the coil set at 90 to the skull. Receives: Device: Theta-burst stimulation (TBS) |
| Cognitively normal control | No intervention | Cognitively normal controls will be recruited for neuroimaging comparison. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: Before and immediately after TBS intervention
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)
Measured: Before and 4 weeks after TBS intervention
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)
Measured: Before and immediately after TBS intervention
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)
Measured: Before and 4 weeks after TBS intervention
Secondary outcomes (1)
The standard uptake values changes of FDG-PET
The standard uptake values (SUV) changes of cerebral glucose metabolism using 18F-FDG-PET
Measured: Before and 1 week after TBS intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2019
- Study start3 Jan 2020
- Primary completion30 Jun 2026
- Study completion30 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer Disease, Early OnsetStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chang Gung Memorial Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- KUAN YI WU, Principal investigator, Chang Gung Memorial Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04042532
- Sponsor's protocol ID
- 201802104A0
- Status last verified
- Oct 2026
- First submitted
- 28 Jul 2019
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04042532
- Acronym / sponsor ID
- 201802104A0
- Conditions
- Alzheimer Disease, Early Onset
- Keywords
- Young-onset dementia, Alzheimer's disease, rTMS, TBS
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Chang Gung Memorial HospitalUniversity, hospital or other
- Study start
- 3 Jan 2020 (actual)
- Primary completion
- 30 Jun 2026 (actual)
- Study completion
- 30 Jun 2026 (actual)
- First posted
- 2 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Active group | Active comparator | Device: Theta-burst stimulation (TBS)Active group will receive active stimulation of standard intermittent TBS (iTBS) protocol. |
| Sham group | Sham comparator | Device: Theta-burst stimulation (TBS)Sham group will receive sham stimulation of the same iTBS protocol with the coil set at 90 to the skull. |
| Cognitively normal control | No intervention | –Cognitively normal controls will be recruited for neuroimaging comparison. |
Who may qualify
- Ages
- 50 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Theta-burst stimulation (TBS)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. | Device | Active group, Sham group |
Primary outcome
Change from baseline MMSE total scores immediately after TBS intervention
Time frame: Before and 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
Time frame: Before and 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
Time frame: Before and 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
Time frame: Before and 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)
1 secondary outcome
The standard uptake values changes of FDG-PET
Time frame: Before and 1 week after TBS intervention
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
KUAN YI WU principal investigator
Chang Gung Memorial Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Theta-burst stimulation (TBS) in people with Alzheimer Disease, Early Onset, run by Chang Gung Memorial Hospital at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline MMSE total scores immediately after TBS intervention (time frame: Before and immediately after TBS intervention). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2026.