Efficacy and Safety of Temporal Interference Stimulation on Cognitive Function in Patients With Early-Stage Alzheimer's Disease

Official title

A Randomized, Double-Blind, Controlled Trial to Evaluate the Efficacy and Safety of Temporal Interference Stimulation on Cognitive Function in Patients With Early-Stage Alzheimer's Disease

Overview

This study aims to investigate the efficacy and safety of a novel non-invasive brain stimulation technique-Temporal Interference Stimulation (TIS)-in patients with early-stage Alzheimer's disease. A total of 40 participants will be randomly assigned to either the TIS group or the sham stimulation group. The intervention will last for 2 weeks, with cognitive and safety assessments at baseline, post-treatment, and 12 weeks after treatment.

Interventions

• Device Temporal Interference Stimulation
  Device: The non-invasive brain stimulator NervioX is used to administer Temporal Interference Stimulation (TIS). Stimulation Parameters: Frequencies: 2000 Hz and 2005 Hz (resulting in a 5 Hz theta rhythm envelope). Stimulation Intensity: 1.0-2.0 mA (peak current). Stimulation Target: Bilateral hippocampus Session Duration: 40 minutes per session. Treatment Course: 5 sessions per week, for 2 consecutive weeks, totaling 10 sessions.
• Device Sham Stimulation
  Device: The same NervioX device is used. Stimulation Parameters: The device is programmed to deliver a real stimulation (1.0-2.0 mA) for the initial 30 seconds of the session to mimic the initial sensation experienced by the active group. Subsequently, the current is automatically reduced to 0 mA for the remainder of the 40-minute session. The device screen continues to display the stimulation as ongoing to maintain the blinding. The session frequency and total course (5 sessions/week for 2

Primary outcome measures

• Changes in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog 11) Score [Time frame: Baseline, End of treatment (2 weeks)]

Secondary outcome measures (9)

• Change in Mini-Mental State Examination (MMSE) Score [Time frame: Baseline, End of treatment (2 weeks), Post-treatment follow-up (12 weeks)]
• Change in Montreal Cognitive Assessment (MoCA) Score [Time frame: Baseline, End of treatment (2 weeks), Post-treatment follow-up (12 weeks)]
• Change in Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score [Time frame: Baseline, End of treatment (2 weeks), Post-treatment follow-up (12 weeks)]
• Change in Shape Trails Test (STT) - Part A Time [Time frame: Baseline, End of treatment (2 weeks), Post-treatment follow-up (12 weeks)]
• Change in Shape Trails Test (STT) - Part B Time [Time frame: Baseline, End of treatment (2 weeks), Post-treatment follow-up (12 weeks)]
• Change in Digit Span Test (DST) Score [Time frame: Baseline, End of treatment (2 weeks), Post-treatment follow-up (12 weeks)]
• Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time frame: From baseline through study completion (up to 16 weeks)]
• Change in Functional Connectivity measured by Resting-state Functional Magnetic Resonance Imaging (rs-fMRI) [Time frame: Baseline, End of treatment (2 weeks), Post-treatment follow-up (12 weeks)]
• Change in Theta Band Power measured by Electroencephalography (EEG) [Time frame: Baseline, End of treatment (2 weeks), Post-treatment follow-up (12 weeks)]

Eligibility criteria

Inclusion Criteria：

• According to the 2024 NIA-AA Revised Criteria , defined as positivity for at least one Core 1 biomarker:

• Positive plasma p-tau217 test (positivity defined by clinically validated diagnostic cutoffs provided by the assay manufacturer); or
• Positive amyloid PET scan; or
• Abnormal cerebrospinal fluid (CSF) ratios, including p-tau181/Aβ42, t-tau/Aβ42, or Aβ42/40.

\*Reference: Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup. Alzheimers Dement. 2024 Aug;20(8):5143-5169.\*

• Age between 50 and 75 years, inclusive.
• Minimum of 6 years of formal education.
• Clinical Dementia Rating (CDR) global score of 0.5 or 1.0.
• MMSE≥21.
• Stable dosage of cognitive-enhancing medications (e.g., cholinesterase inhibitors and/or memantine) for at least 6 weeks prior to screening.

Exclusion criteria

• Current or past history of significant neurological disorders other than AD (e.g., epilepsy, stroke, multiple sclerosis), intracranial lesions, neurosurgery, or significant head trauma.
• Current use of medications that may substantially impair cognitive function (e.g., anticonvulsants, antipsychotics, benzodiazepines).
• Any contraindication for MRI or the stimulation device (e.g., metallic implants, pacemakers, severe claustrophobia).
• Significant structural brain abnormalities on MRI (e.g., hydrocephalus, stroke, or severe white matter lesions \[Fazekas score ≥ 3\]).
• Diagnosis of major depression or other active, uncontrolled psychiatric disorders.
• Any severe or unstable medical condition that, in the investigator's judgment, could compromise participant safety or study validity (e.g., cardiovascular, renal, hepatic, respiratory, active cancer), or a history of alcohol/substance dependence.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine — Shanghai

Identifiers

NCT: NCT07543094 · 2025-621

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗