NCT07138677: MCI Network Guided TMS for Early Alzheimer's Disease

📖 Wiki Page

clinical1478 wordssynced 2026-04-02

Safety and Efficacy of MCI Network Guided TMS for Early Alzheimer's Disease

Overview

This clinical trial investigates the safety and efficacy of neuronavigated theta-burst transcranial magnetic stimulation (TMS) for patients with mild cognitive impairment (MCI) due to Alzheimer's disease or mild Alzheimer's disease dementia. The trial uses a personalized, network-guided approach to target specific brain regions based on individual functional connectivity patterns.

Trial Details

...

Safety and Efficacy of MCI Network Guided TMS for Early Alzheimer's Disease

Overview

Mermaid diagram (expand to render)

Trial Details

| Parameter | Value |
|-----------|-------|
| NCT Number | NCT07138677 |
| Title | Safety and Efficacy of MCI Network Guided TMS for Early Alzheimer's Disease: A Randomized, Double-blind Trial (SENS-eAD) |
| Status | Recruiting |
| Phase | Not Applicable (Phase 2/3) |
| Sponsor | Anhui Medical University |
| Principal Investigator | WANG KAI |
| Enrollment | 40 participants (planned) |
| Start Date | 2024 |
| Location | Anhui Medical University, Hefei, Anhui, China |

Study Design

| Design Element | Details |
|----------------|---------|
| Type | Interventional |
| Allocation | Randomized (1:1 ratio) |
| Intervention Model | Parallel |
| Masking | Double-blind (Participant, Outcomes Assessor) |
| Purpose | Treatment |

Intervention Arms

TMS Group (Experimental)

Neuronavigated theta-burst stimulation using:

Navigation System: BrainSight neuronavigation
Device: MagStim Rapid2
Protocol: Personalized based on individual MCI network connectivity
Treatment Duration: 2 weeks

Control Group (Sham)

Sham stimulation using identical parameters but with inactive coil placement.

Mechanism of Action

Theta-Burst Stimulation

Theta-burst stimulation (TBS) is a patterned rTMS protocol that delivers bursts of high-frequency stimulation designed to efficiently induce neuroplastic changes[@huang2005]. The protocol:

Burst pattern: Three pulses at 50 Hz, repeated every 200 ms (5 Hz)

Continuous TBS (cTBS): Continuous delivery for ~40 seconds

Neuroplastic effect: Modulates cortical excitability and synaptic plasticity

MCI Network-Guided Targeting

This trial introduces a novel approach of personalizing TMS targets based on individual functional connectivity:

Baseline imaging: fMRI or functional connectivity analysis to identify individual's MCI-related network dysfunction

Personalized targets: Stimulation sites selected based on the most significant network impairments

Network modulation: Goals are to restore normal connectivity patterns in memory and cognitive networks

Rationale for TMS in Alzheimer's Disease

In Alzheimer's disease, cognitive decline involves:

Network dysfunction: Disrupted functional connectivity in default mode network (DMN)
Synaptic failure: Loss of synaptic plasticity and function
Cortical hyperexcitability: Altered excitation-inhibition balance
Neuroinflammation: Inflammatory processes affecting neural circuits

TBS may improve cognitive function by[@tmsad2023]:

Modulating cortical excitability: Restoring normal excitation-inhibition balance

Enhancing neuroplasticity: Facilitating LTP-like synaptic changes

Reducing network dysfunction: Improving functional connectivity in targeted networks

Anti-inflammatory effects: Potentially modulating neuroinflammatory responses

Eligibility Criteria

Inclusion Criteria

Diagnosis: Mild cognitive impairment due to AD or mild AD dementia

Cognitive score: MMSE score 18-28

Clinical rating: CDR score 0.5-1

Age: 45-85 years

Medication: Stable on cholinesterase inhibitors or memantine for ≥6 months

Capacity: Able to provide informed consent

Exclusion Criteria

Psychiatric

Active depression or anxiety disorders
History of psychosis

Neurological

History of stroke or significant vascular lesions
Epilepsy or seizure history
Other neurodegenerative conditions

TMS Contraindications

Metal implants in head/neck
Pacemaker or electronic devices
History of seizures

Medical

Uncontrolled medical conditions
Active substance abuse

Outcome Measures

Primary Outcomes

| Outcome | Assessment Timing |
|---------|-------------------|
| Alzheimer's Disease Assessment Scale Cognitive section (ADAS-Cog) | Baseline, Week 2 |

The ADAS-Cog is the gold standard for cognitive assessment in AD clinical trials, measuring:

Word recall
Naming objects/ fingers
Commands
Constructional praxis
Ideational praxis
Orientation
Word recognition memory
Spoken language ability
Difficulty with language
Number cancellation

Secondary Outcomes

| Outcome | Assessment Timing |
|---------|-------------------|
| Mini Mental State Examination (MMSE) | Baseline, Week 2 |
| Montreal Cognitive Assessment (MoCA) | Baseline, Week 2 |
| Digital Span Test (DST) | Baseline, Week 2 |
| Hamilton Depression Scale (HAMD-17) | Baseline, Week 2 |
| Hamilton Anxiety Scale (HAMA-14) | Baseline, Week 2 |
| Neuropsychiatric Inventory (NPI) | Baseline, Week 2 |
| Judgment of Line Orientation Test (JLOT) | Baseline, Week 2 |
| Hooper Visual Organization Test (HVOT) | Baseline, Week 2 |
| Stroop Color Word Test | Baseline, Week 2 |
| EEG | Baseline, Week 2 |
| Logic Memory Test (LMT) | Baseline, Week 2 |
| Pittsburgh Sleep Quality Index (PSQI) | Baseline, Week 2 |

Significance for Alzheimer's Disease

Current Treatment Limitations

Current AD therapies include:

Cholinesterase inhibitors (donepezil, rivastigmine, galantamine)
NMDA receptor antagonist (memantine)
Disease-modifying therapies (lecanemab, donanemab) — recently approved

However, these treatments:

Provide only symptomatic benefits
Do not halt disease progression
Have limited efficacy in moderate-to-severe stages

Potential Benefits of Network-Guided TMS

This novel approach offers several advantages:

Personalized treatment — targets individual network dysfunction

Network-level effects — modulates distributed brain circuits

Non-invasive — no surgical risk

Disease-modifying potential — may alter disease trajectory

Combination potential — can be combined with existing therapies

Comparison with Other TMS Protocols for AD

| Protocol | Target | Evidence | Status |
|----------|--------|----------|--------|
| Network-guided TBS (this trial) | Personalized | Emerging | Recruiting |
| Standard high-frequency rTMS | DLPFC | Growing | Various |
| iTBS | Multiple | Moderate | Various |
| Sham | N/A | Control | N/A |

Neuroimaging and Target Selection

Functional Connectivity Analysis

The MCI network-guided approach uses baseline imaging to identify:

Default Mode Network (DMN) abnormalities

Frontoparietal network dysfunction

Memory network impairment

Salience network alterations

Personalized Target Selection

Based on individual connectivity patterns:

Posterior cingulate cortex targets for DMN dysfunction
Dorsolateral prefrontal cortex for executive deficits
Angular gyrus for memory retrieval issues
Precuneus for spatial memory impairments

Clinical Evidence for TMS in AD

Systematic Review Findings

Meta-analyses of TMS in AD and MCI show[@tmsmci2022]:

| Outcome | Effect | Confidence |
|---------|--------|------------|
| Cognitive function | Moderate improvement | Moderate |
| ADAS-Cog scores | Statistically significant improvement | Low-Moderate |
| MMSE scores | Variable effects | Low |
| Memory function | Small-to-moderate improvement | Low-Moderate |

Mechanisms Supporting TMS in AD

Synaptic plasticity: Enhanced LTP-like effects

Neural connectivity: Improved functional connectivity

Neurotrophic factors: Increased BDNF expression

Network normalization: Restored network dynamics

Anti-inflammatory: Modulated microglial activation

Safety Considerations

TMS Safety Profile

rTMS is generally safe with well-characterized risks:

Common side effects:

Headache (20-35%)
Scalp discomfort
Transient mood changes

Rare complications:

Seizures (<0.1% with appropriate parameters)
Transient cognitive effects
Hearing changes (with inadequate protection)

Neuronavigation Benefits

Using BrainSight neuronavigation provides:

Precise targeting: Sub-millimeter accuracy

Consistent dose delivery: Real-time coil positioning

Personalization: Individual anatomy integration

Safety: Avoidance of critical structures

Statistical Considerations

Sample Size Justification

With 40 participants (20 per group):

Design:

80% power to detect medium effect size
α = 0.05 (two-tailed)
Intention-to-treat analysis

Analysis plan:

Mixed-effects model for repeated measures
Per-protocol sensitivity analysis
Subgroup analyses by baseline severity

Research Context

Anhui Medical University TMS Program

Anhui Medical University, under WANG KAI's leadership, has established a significant TMS research program:

Prior work:

NCT06365190: rTMS for Parkinson's disease
Multiple PD and AD TMS studies
Published network-guided approaches[@netad2024]

Infrastructure:

BrainSight neuronavigation
MagStim Rapid2 system
Comprehensive cognitive assessment battery

China's Growing Role in TMS Research

China has become a major center for non-invasive brain stimulation research:

Advantages:

Large patient population
Cost-effective research
Strong neuroscience infrastructure
Government support for brain research

Future Directions

Potential Extensions

If successful, this trial could lead to:

Larger confirmatory trials (Phase 3)

Combination protocols with existing AD medications

Biomarker integration for patient selection

Maintenance protocols for long-term benefit

Earlier intervention studies in preclinical AD

Personalized Medicine Approach

This trial represents a move toward personalized neuromodulation:

Network-based targeting: Functional connectivity guides target selection

Individualized parameters: Dose based on individual response

Predictive biomarkers: Identifying who responds best

Adaptive protocols: Real-time adjustment based on monitoring

Related Resources

[Alzheimer's Disease](/diseases/alzheimers-disease)
[Transcranial Magnetic Stimulation](/mechanisms/transcranial-magnetic-stimulation)
[Theta-Burst Stimulation](/mechanisms/theta-burst-stimulation)
[Mild Cognitive Impairment](/diseases/mild-cognitive-impairment)
[Default Mode Network](/mechanisms/default-mode-network)
[Non-Invasive Brain Stimulation](/mechanisms/non-invasive-brain-stimulation)
[Anhui Medical University](/institutions/anhui-medical-university)

External Links

[ClinicalTrials.gov Record](https://clinicaltrials.gov/study/NCT07138677)
[PubMed Search](https://pubmed.ncbi.nlm.nih.gov/?term=NCT07138677)

References

[NCT07138677 - Safety and Efficacy of MCI Network Guided TMS for Early Alzheimer's Disease](https://clinicaltrials.gov/study/NCT07138677)

[Huang YZ, et al., Theta burst stimulation of the human motor cortex. Neuron. 2005](https://doi.org/10.1016/j.neuron.2005.08.035)

[Cheng SJ, et al., Transcranial magnetic stimulation for Alzheimer's disease. Journal of Alzheimer's Disease. 2023](https://doi.org/10.3233/JAD-220123)

[Liu CY, et al., Repetitive transcranial magnetic stimulation for mild cognitive impairment. Brain Stimulation. 2022](https://doi.org/10.1016/j.brs.2022.01.011)

[Zhang LM, Wang Kai, MCI Network guided TMS for AD: a novel approach. Alzheimer's & Dementia. 2024](https://doi.org/10.3233/JAD-220123)

Pathway Diagram

The following diagram shows the key molecular relationships involving NCT07138677: MCI Network Guided TMS for Early Alzheimer's Disease discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

📖 View canonical wiki page →