Mild Cognitive ImpairmentPhase 2NCT04555941
The Effects of Intermittent Theta Burst Stimulation in MCI and Early AD
A Phase 2 study testing intermittent theta burst stimulation in people with Mild Cognitive Impairment and Alzheimer Disease, run by Taipei Medical University Shuang Ho Hospital at 1 site in Taiwan.
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… Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Mild Cognitive Impairment, Alzheimer Disease, Cognitive Decline
- What is being tested?
- intermittent theta burst stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 54 participants
- Where
- 1 siteTaiwan
- Study dates
- 5 Oct 2020to 31 Jan 2022
- Phase
- Phase 2
- 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 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- normal visual acuity
- diagnosed with mild cognitive impairment or early dementia due to Alzheimer's disease (CDR = 0.5) by neurologists
Who cannot join
- (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
Show all 11Show fewer
- metal implants
- taking medication lowering the threshold of seizure attacks
- fear of using TMS
- with specific allergens
- pregnant or breastfeeding women
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Cognitive Effects of Theta Burst Stimulation in Mild Cognitive Impairment and Alzheimer's Disease
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.
Read the detailed 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
- Being tested
- intermittent theta burst stimulation
- Keywords
- Transcranial magnetic stimulation, non-invasive brain stimulation
- Medical subject headings
- Cognitive Dysfunction, Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
intermittent theta burst stimulationDevice
Also called Magstim rapid 2
active or Sham iTBS will be given to the AD/MCI patient
| Study group | Role | What they receive |
|---|---|---|
| active iTBS | Experimental | The patient is treated with iTBS stimulation according to protocol with an active coil. Receives: Device: intermittent theta burst stimulation |
| Sham iTBS | Sham comparator | The patient is treated with Sham-iTBS stimulation according to protocol with an inactive coil. Receives: Device: intermittent theta burst stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Baseline, immediate post-iTBS, follow-up (4 weeks post-iTBS)
Secondary outcomes (1)
Brain MRI
Change in white matter and brain activities at resting state at baseline compared to after iTBS stimulation
Measured: Baseline, immediate post-iTBS, follow-up (4 weeks post-iTBS)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2020
- Study start5 Oct 2020
- Primary completion31 Jan 2022
- Study completion31 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Mild Cognitive ImpairmentStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- Taipei Medical University Shuang Ho Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Cheng-Chang Yang, Taipei Medical University Shuang Ho Hospital
- Investigators
- Yi-Chun Kuan, MD, Principal investigator, Taipei Medical University Shuang Ho Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04555941
- Sponsor's protocol ID
- N202003022
- Status last verified
- Oct 2022
- First submitted
- 25 Aug 2020
- Last updated
- 26 Oct 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Yang CC, Huang KY, Hsu JL, Hu CJ, Lu YH, Kuan YC. Effects of intermittent theta-burst stimulation on cognition and glymphatic system activity in mild cognitive impairment and very mild Alzheimer's disease: a randomized controlled trial. J Neuroeng Rehabil. 2025 Sep 26;22(1):195. doi: 10.1186/s12984-025-01738-1.
PubMed 41013466
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cognitive Effects of Theta Burst Stimulation in Mild Cognitive Impairment and Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT04555941
- Acronym / sponsor ID
- N202003022
- Keywords
- Transcranial magnetic stimulation, non-invasive brain stimulation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- Taipei Medical University Shuang Ho HospitalUniversity, hospital or other
- Study start
- 5 Oct 2020 (actual)
- Primary completion
- 31 Jan 2022 (actual)
- Study completion
- 31 Jan 2022 (actual)
- First posted
- 21 Sep 2020 (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.
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.
Detailed 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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| active iTBS | Experimental | Device: intermittent theta burst stimulationThe patient is treated with iTBS stimulation according to protocol with an active coil. |
| Sham iTBS | Sham comparator | Device: intermittent theta burst stimulationThe patient is treated with Sham-iTBS stimulation according to protocol with an inactive coil. |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- normal visual acuity
- diagnosed with mild cognitive impairment or early dementia due to Alzheimer's disease (CDR = 0.5) by neurologists
Key exclusion criteria (11 listed)
- (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)
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 |
|---|---|---|
| intermittent theta burst stimulationAlso: Magstim rapid 2active or Sham iTBS will be given to the AD/MCI patient | Device | Sham iTBS, active iTBS |
Primary outcome
Changes from baseline in scores of any tests of the Neuropsychological Battery
Time frame: Baseline, immediate post-iTBS, follow-up (4 weeks post-iTBS)
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
1 secondary outcome
Brain MRI
Time frame: Baseline, immediate post-iTBS, follow-up (4 weeks post-iTBS)
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 26 Oct 2022.
- Derived from this study: PubMed 41013466Yang CC, Huang KY, Hsu JL, Hu CJ, Lu YH, Kuan YC. Effects of intermittent theta-burst stimulation on cognition and glymphatic system activity in mild cognitive impairment and very mild Alzheimer's disease: a randomized controlled trial. J Neuroeng Rehabil. 2025 Sep 26;22(1):195. doi: 10.1186/s12984-025-01738-1.
- 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.
Yi-Chun Kuan, MD principal investigator
Taipei Medical University Shuang Ho Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing intermittent theta burst stimulation in people with Mild Cognitive Impairment and Alzheimer Disease, run by Taipei Medical University Shuang Ho 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 2 inclusion and 11 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 26 Oct 2022. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Changes from baseline in scores of any tests of the Neuropsychological Battery (time frame: Baseline, immediate post-iTBS, follow-up (4 weeks post-iTBS)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04555941, which also lists 1 linked publication.
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 26 Oct 2022.