MCI-AD, Early Stage Alzheimer's DiseaseNCT07196592
Development of a Novel Multidimensional Therapeutic Intervention Protocol for MCI
A study testing Olfactory stimulation, Temporal Interference,TI and Olfactory-TI Stimulation in people with MCI-AD, Early Stage Alzheimer's Disease, run by Yuan Shen.
Trial summary
As populations age, Alzheimer's disease (AD) is increasing while disease-modifying drugs remain elusive, making early diagnosis and intervention essential. Building on advances in neuromodulation and virtual reality (VR), we target amnestic mild cognitive impairment (aMCI)-the prodromal stage of AD-as a key window for… Read more about this study
- Who is it for?
- Ages 60 years and olderHealthy volunteers can take part
- Conditions the study is for
- MCI-AD, Early Stage Alzheimer's Disease
- What is being tested?
- Olfactory stimulation, Temporal Interference,TI and Olfactory-TI Stimulation
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 300 participants
- Where
- No sites listed yet
- Study dates
- 1 Oct 2025to 1 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 60 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Baseline screening inclusion criteria: a) Age ≤ 65 years and ≤ 85 years; b) Education duration ≥ 1 year; c) Normal cognitive function at enrollment: MMSE total score: non-illiterate (primary school or below) ≥ 20 points, primary school or above ≥ 24 points; d) Corrected vision and hearing are basically normal, and able to complete cognitive assessment.
Who cannot join
- Baseline screening exclusion criteria: a) Neurological/psychiatric disorders affecting cognitive function: depression, schizophrenia, mental retardation, Parkinson's disease, etc.; b) Severe physical illnesses: cardiovascular disease, cerebrovascular disease, tumors, diabetes, kidney disease, and hypertension stage III or above; c) Autoimmune inflammatory diseases such as rheumatoid arthritis, lupus erythematosus, osteoarthritis, and multiple sclerosis.
About this study
Official title: AD New Multi-Dimensional Therapy Device Development - Microcurrent Brain Stimulation Device and Virtual Reality Therapy Equipment
As populations age, Alzheimer's disease (AD) is increasing while disease-modifying drugs remain elusive, making early diagnosis and intervention essential. Building on advances in neuromodulation and virtual reality (VR), we target amnestic mild cognitive impairment (aMCI)-the prodromal stage of AD-as a key window for prevention. Preliminary evidence shows disrupted theta-delta phase-amplitude coupling in prefrontal and temporal cortices in aMCI, whereas olfactory enrichment can enhance hippocampal synaptic function, improve cognition, and potentially lower AD risk. We will conduct a large-scale clinical cohort study to test the neural mechanisms and clinical efficacy of multi-site, cross-frequency transcranial alternating current stimulation (tACS) combined with multisensory (visual-olfactory-auditory) VR. A comprehensive database spanning demographic, neuropsychological, biochemical, neuroimaging, and neuromodulation parameters will guide optimal protocols and provide objective evidence for non-pharmacological interventions, informing development of a microcurrent brain stimulator and a portable VR device.
Read the detailed description
With the accelerating pace of population aging, the prevalence of Alzheimer's disease (AD) continues to rise, yet effective disease-modifying pharmacotherapies remain unavailable. Early diagnosis and intervention are critical to slowing cognitive decline and reducing disease burden. In recent years, rapid advances in neuromodulation and virtual reality (VR) have opened new avenues for mechanistic studies and functional brain rehabilitation in AD and other neurodegenerative disorders. Amnestic mild cognitive impairment (aMCI) is widely regarded as the prodromal stage of AD and represents a key window for prevention and treatment. Developing innovative non-pharmacological therapies for individuals at this early stage has therefore become an urgent clinical priority. Preliminary studies indicate that people with aMCI exhibit a significant loss of phase-amplitude coupling (PAC) between theta and delta rhythms in the prefrontal cortex and temporal lobe, whereas olfactory-enriched environmental stimulation can enhance hippocampal synaptic function, improve cognition, and lower AD risk. Accordingly, we propose a large-scale clinical cohort study to investigate the neural-circuit mechanisms and clinical efficacy of multi-site, cross-frequency transcranial alternating current stimulation (tACS) and multisensory VR integrating visual, olfactory, and auditory inputs for the treatment of aMCI. We will establish a comprehensive database encompassing demographic, neuropsychological, biochemical, neuroimaging, and neuromodulation parameters. Ultimately, this work will provide optimal theoretical parameters and objective evidence to guide the development of non-pharmacological interventions for AD-specifically, a microcurrent brain stimulator and a portable VR device.
- Being tested
- Olfactory stimulation, Temporal Interference,TI, Olfactory-TI Stimulation, Sham Control
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Olfactory stimulationBehavioural
Olfactory stimulation were set as follows:
Essential oil types: yuzu, lavender, lemon, and mint. Concentration: 158 μL of essential oil + 50 mL of water. The mixed solution was poured into the test tubes of the olfactory instrument, ensuring that the liquid levels of the four solutions were kept at the same height. Each scent was released for 30 seconds, followed by a 10-second air interval, with each cycle lasting 20 minutes.
Temporal Interference,TIBiological
During stimulation, the parameters were set as follows:
Δf=40Hz (2000Hz vs. 2040Hz) 2mA Stimulation duration: 20min We fixed the stimulation protocol and used a standard head to simulate stimulation of the entorhinal region.
Olfactory-TI StimulationCombination product
During stimulation, the parameters were set as follows:
Δf=40Hz (2000Hz vs. 2040Hz) 2mA Stimulation duration: 20min We fixed the stimulation protocol and used a standard head to simulate stimulation of the entorhinal region.
Olfactory stimulation were set as follows:
Essential oil types: yuzu, lavender, lemon, and mint. Concentration: 158 μL of essential oil + 50 mL of water. The mixed solution was poured into the test tubes of the olfactory instrument, ensuring that the liquid levels of the four solutions were kept at the same height. Each scent was released for 30 seconds, followed by a 10-second air interval, with each cycle lasting 20 minutes.
Sham ControlCombination product
During stimulation, the parameters were set as follows:
Δf=0Hz (2000Hz vs. 2000Hz) 2mA Stimulation duration: 20min.
Olfactory stimulation were set as follows:
Essential oil types: air. lasting 20 minutes.
| Study group | Role | What they receive |
|---|---|---|
| Olfactory Stimulation Group | Experimental | Not described Receives: Behavioral: Olfactory stimulation |
| TI Stimulation Group | Experimental | Not described Receives: Biological: Temporal Interference,TI |
| Olfactory-TI Stimulation Group | Experimental | Not described Receives: Combination Product: Olfactory-TI Stimulation |
| Sham Control Group | Sham comparator | Not described Receives: Combination Product: Sham Control |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Olfactory Sensitivity (TDI score)
Change in olfactory function measured with the Sniffin' Sticks Threshold-Discrimination-Identification (TDI) composite score.
Unit of Measure: TDI score, 1-48 (higher scores indicate better olfactory function).
Measured: Baseline; 30 minutes after Session 1; 30 minutes after Session 5; 30 minutes after Session 10; 1 week after Session 10.
Path Integration - Angle Deviation
Absolute angular error during the path-integration task. Lower values indicate better performance.
Unit of Measure: Degrees (°); lower is better.
Measured: Baseline; 5 minutes after Session 1; 5 minutes after Session 5; 5 minutes after Session 10.
Path Integration - Distance Deviation
Difference between actual and ideal path length during the path-integration task. Lower values indicate better performance.
Unit of Measure: Meters (m); lower is better.
Measured: Baseline; 5 minutes after Session 1; 5 minutes after Session 5; 5 minutes after Session 10.
Path Integration - Composite Accuracy (M_ROC_AUC)
Area under the ROC curve computed from multivariate PI features to quantify task accuracy/reliability across sessions.
Unit Measure: AUC, 0.00-1.00 (higher values indicate better accuracy/stability).
Measured: Baseline; 5 minutes after Session 1; 5 minutes after Session 5; 5 minutes after Session 10.
Change in Cognitive Performance (MoCA-B)
Change in global cognition using the Montreal Cognitive Assessment-Basic (MoCA-B).
Unit of Measure: MoCA-B score, 0-30 (higher scores indicate better cognition).
Measured: Baseline; 5 minutes after Session 10.
Secondary outcomes (2)
Activities of Daily Living (ADL - Barthel Index)
Change in functional ability using the Barthel Index. Unit of Measure: Barthel Index, 0-100 (higher scores indicate greater independence).
Measured: Baseline; 30 minutes after Session 1; 30 minutes after Session 5; 30 minutes after Session 10; 1 week after Session 10.
Adverse Events Related to Intervention
Incidence of device- or procedure-related adverse events (e.g., skin irritation, headache, dizziness, nausea).
Unit of Measure: Number of participants with ≥1 adverse event (count).
Measured: Baseline; 5 minutes after Session 1; 5 minutes after Session 5; 5 minutes after Session 10.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2025
- Study start1 Oct 2025 (estimated)
- Primary completion1 Nov 2026 (estimated)
- Study completion1 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MCI-AD, Early Stage Alzheimer's DiseaseStudies 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
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yuan Shen
- Sponsor type
- University, hospital or other
- Collaborators
- Shanghai Mental Health Center
- Responsible party
- Sponsor-investigator, Yuan Shen, Tongji University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07196592
- Sponsor's protocol ID
- B20250001I
- Status last verified
- Sep 2025
- First submitted
- 15 Sep 2025
- Last updated
- 29 Sep 2025
- Results posted
- 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 29 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- AD New Multi-Dimensional Therapy Device Development - Microcurrent Brain Stimulation Device and Virtual Reality Therapy Equipment
- ClinicalTrials.gov ID
- NCT07196592
- Acronym / sponsor ID
- B20250001I
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Yuan ShenUniversity, hospital or other
- Collaborators
- Shanghai Mental Health Center
- Study start
- 1 Oct 2025 (estimated)
- Primary completion
- 1 Nov 2026 (estimated)
- Study completion
- 1 Dec 2026 (estimated)
- First posted
- 29 Sep 2025 (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.
As populations age, Alzheimer's disease (AD) is increasing while disease-modifying drugs remain elusive, making early diagnosis and intervention essential. Building on advances in neuromodulation and virtual reality (VR), we target amnestic mild cognitive impairment (aMCI)-the prodromal stage of AD-as a key window for prevention. Preliminary evidence shows disrupted theta-delta phase-amplitude coupling in prefrontal and temporal cortices in aMCI, whereas olfactory enrichment can enhance hippocampal synaptic function, improve cognition, and potentially lower AD risk. We will conduct a large-scale clinical cohort study to test the neural mechanisms and clinical efficacy of multi-site, cross-frequency transcranial alternating current stimulation (tACS) combined with multisensory (visual-olfactory-auditory) VR. A comprehensive database spanning demographic, neuropsychological, biochemical, neuroimaging, and neuromodulation parameters will guide optimal protocols and provide objective evidence for non-pharmacological interventions, informing development of a microcurrent brain stimulator and a portable VR device.
Detailed description
With the accelerating pace of population aging, the prevalence of Alzheimer's disease (AD) continues to rise, yet effective disease-modifying pharmacotherapies remain unavailable. Early diagnosis and intervention are critical to slowing cognitive decline and reducing disease burden. In recent years, rapid advances in neuromodulation and virtual reality (VR) have opened new avenues for mechanistic studies and functional brain rehabilitation in AD and other neurodegenerative disorders. Amnestic mild cognitive impairment (aMCI) is widely regarded as the prodromal stage of AD and represents a key window for prevention and treatment. Developing innovative non-pharmacological therapies for individuals at this early stage has therefore become an urgent clinical priority. Preliminary studies indicate that people with aMCI exhibit a significant loss of phase-amplitude coupling (PAC) between theta and delta rhythms in the prefrontal cortex and temporal lobe, whereas olfactory-enriched environmental stimulation can enhance hippocampal synaptic function, improve cognition, and lower AD risk. Accordingly, we propose a large-scale clinical cohort study to investigate the neural-circuit mechanisms and clinical efficacy of multi-site, cross-frequency transcranial alternating current stimulation (tACS) and multisensory VR integrating visual, olfactory, and auditory inputs for the treatment of aMCI. We will establish a comprehensive database encompassing demographic, neuropsychological, biochemical, neuroimaging, and neuromodulation parameters. Ultimately, this work will provide optimal theoretical parameters and objective evidence to guide the development of non-pharmacological interventions for AD-specifically, a microcurrent brain stimulator and a portable VR device.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Olfactory Stimulation Group | Experimental | Behavioral: Olfactory stimulation |
| TI Stimulation Group | Experimental | Biological: Temporal Interference,TI |
| Olfactory-TI Stimulation Group | Experimental | Combination Product: Olfactory-TI Stimulation |
| Sham Control Group | Sham comparator | Combination Product: Sham Control |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Baseline screening inclusion criteria: a) Age ≤ 65 years and ≤ 85 years; b) Education duration ≥ 1 year; c) Normal cognitive function at enrollment: MMSE total score: non-illiterate (primary school or below) ≥ 20 points, primary school or above ≥ 24 points; d) Corrected vision and hearing are basically normal, and able to complete cognitive assessment.
Key exclusion criteria (1 listed)
- Baseline screening exclusion criteria: a) Neurological/psychiatric disorders affecting cognitive function: depression, schizophrenia, mental retardation, Parkinson's disease, etc.; b) Severe physical illnesses: cardiovascular disease, cerebrovascular disease, tumors, diabetes, kidney disease, and hypertension stage III or above; c) Autoimmune inflammatory diseases such as rheumatoid arthritis, lupus erythematosus, osteoarthritis, and multiple sclerosis.
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 |
|---|---|---|
| Olfactory stimulationOlfactory stimulation were set as follows: Essential oil types: yuzu, lavender, lemon, and mint. Concentration: 158 μL of essential oil + 50 mL of water. The mixed solution was poured into the test tubes of the olfactory instrument, ensuring that the liquid levels of the four solutions were kept at the same height. Each scent was released for 30 seconds, followed by a 10-second air interval, with each cycle lasting 20 minutes. | Behavioural | Olfactory Stimulation Group |
| Temporal Interference,TIDuring stimulation, the parameters were set as follows: Δf=40Hz (2000Hz vs. 2040Hz) 2mA Stimulation duration: 20min We fixed the stimulation protocol and used a standard head to simulate stimulation of the entorhinal region. | Biological | TI Stimulation Group |
| Olfactory-TI StimulationDuring stimulation, the parameters were set as follows: Δf=40Hz (2000Hz vs. 2040Hz) 2mA Stimulation duration: 20min We fixed the stimulation protocol and used a standard head to simulate stimulation of the entorhinal region. Olfactory stimulation were set as follows: Essential oil types: yuzu, lavender, lemon, and mint. Concentration: 158 μL of essential oil + 50 mL of water. The mixed solution was poured into the test tubes of the olfactory instrument, ensuring that the liquid levels of the four solutions were kept at the same height. Each scent was released for 30 seconds, followed by a 10-second air interval, with each cycle lasting 20 minutes. | Combination product | Olfactory-TI Stimulation Group |
| Sham ControlDuring stimulation, the parameters were set as follows: Δf=0Hz (2000Hz vs. 2000Hz) 2mA Stimulation duration: 20min. Olfactory stimulation were set as follows: Essential oil types: air. lasting 20 minutes. | Combination product | Sham Control Group |
Primary outcome
Change in Olfactory Sensitivity (TDI score)
Time frame: Baseline; 30 minutes after Session 1; 30 minutes after Session 5; 30 minutes after Session 10; 1 week after Session 10.
Change in olfactory function measured with the Sniffin' Sticks Threshold-Discrimination-Identification (TDI) composite score. Unit of Measure: TDI score, 1-48 (higher scores indicate better olfactory function).
Path Integration - Angle Deviation
Time frame: Baseline; 5 minutes after Session 1; 5 minutes after Session 5; 5 minutes after Session 10.
Absolute angular error during the path-integration task. Lower values indicate better performance. Unit of Measure: Degrees (°); lower is better.
Path Integration - Distance Deviation
Time frame: Baseline; 5 minutes after Session 1; 5 minutes after Session 5; 5 minutes after Session 10.
Difference between actual and ideal path length during the path-integration task. Lower values indicate better performance. Unit of Measure: Meters (m); lower is better.
Path Integration - Composite Accuracy (M_ROC_AUC)
Time frame: Baseline; 5 minutes after Session 1; 5 minutes after Session 5; 5 minutes after Session 10.
Area under the ROC curve computed from multivariate PI features to quantify task accuracy/reliability across sessions. Unit Measure: AUC, 0.00-1.00 (higher values indicate better accuracy/stability).
Change in Cognitive Performance (MoCA-B)
Time frame: Baseline; 5 minutes after Session 10.
Change in global cognition using the Montreal Cognitive Assessment-Basic (MoCA-B). Unit of Measure: MoCA-B score, 0-30 (higher scores indicate better cognition).
2 secondary outcomes
Activities of Daily Living (ADL - Barthel Index)
Time frame: Baseline; 30 minutes after Session 1; 30 minutes after Session 5; 30 minutes after Session 10; 1 week after Session 10.
Adverse Events Related to Intervention
Time frame: Baseline; 5 minutes after Session 1; 5 minutes after Session 5; 5 minutes after Session 10.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2025.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A study testing Olfactory stimulation, Temporal Interference,TI and Olfactory-TI Stimulation in people with MCI-AD, Early Stage Alzheimer's Disease, run by Yuan Shen.
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 1 inclusion and 1 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: opening soon, as of the sponsor's last update on 29 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
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?
This study is still under way. Results are not available in the source record yet.
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 in Olfactory Sensitivity (TDI score) (time frame: Baseline; 30 minutes after Session 1; 30 minutes after Session 5; 30 minutes after Session 10; 1 week after Session 10.). The study lists 5 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 29 Sep 2025.