Development of a Novel Multidimensional Therapeutic Intervention Protocol for MCI

NCT07196592 | Not Yet Recruiting

• 1 other identifier: B20250001I
• Study Type: interventional
• Target: 300
• Locations: 0 countries
• Sites: N/A

Brief 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 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.

Conditions

MCI-AD, Early Stage Alzheimer's Disease

Outcome Measures

Primary Outcomes (5)

• 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).

  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.

  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.

  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).

  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).

  Baseline; 5 minutes after Session 10.

Secondary Outcomes (2)

• Activities of Daily Living (ADL - Barthel Index)

  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

  Baseline; 5 minutes after Session 1; 5 minutes after Session 5; 5 minutes after Session 10.

Study Arms (4)

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

Interventions

Olfactory stimulation BEHAVIORAL

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.

Olfactory Stimulation Group

Temporal Interference,TI BIOLOGICAL

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.

TI Stimulation Group

Olfactory-TI Stimulation COMBINATION_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.

Olfactory-TI Stimulation Group

Sham Control COMBINATION_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.

Sham Control Group

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

Sponsors & Collaborators

• Yuan Shen: lead
• Shanghai Mental Health Center: collaborator

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD., Ph.D.

Study Record Dates

• First Submitted: September 15, 2025
• First Posted: September 29, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: September 29, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share