Transcutaneous Auricular Vagus Nerve Stimulation in Type 2 Diabetes With Mild Cognitive Impairment

NCT07642518 | Not Yet Recruiting DMC

• 1 other identifier: 2026-0451-01
• Study Type: interventional
• Target: 38
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is a 24-week, single-center, randomized, double-blind, sham-controlled, parallel-group clinical trial. A total of 38 patients with type 2 diabetes and mild cognitive impairment were enrolled and randomly assigned in a 1:1 ratio to either the treatment group (receiving active transcutaneous auricular vagus nerve stimulation) or the sham control group (receiving sham transcutaneous auricular vagus nerve stimulation). The primary objective of this study is to evaluate the potential disease-modifying effects of transcutaneous auricular vagus nerve stimulation on cognitive impairment in patients with type 2 diabetes.

Conditions

Type 2 Diabetes; Mild Cognitive Impairment

Keywords

Type 2 Diabetes; Mild Cognitive Impairment; Cognitive Impairment; Transcutaneous Auricular Vagus Nerve Stimulation

Outcome Measures

Primary Outcomes (1)

• Montreal Cognitive Assessment Scale (MoCA) score

  The MoCA is a comprehensive endpoint focusing on the cognitive domain. It integrates multidimensional assessments of core cognitive functions (including subscale scores for visuospatial/executive function, naming, attention, language, abstraction, delayed recall, and orientation), yielding a total score range of 0-30.The calculation formula is:MoCA Score = Subscale Scores+ Educational Correction(Note: If the participant's formal education is ≤12 years, 1 point is added to the sum of the subscale scores, with the maximum total score capped at 30).Lower MoCA scores indicate more severe global cognitive impairment in the participant.

  Baseline, and Week 24

Secondary Outcomes (20)

• Change in score of Mini-Mental State Examination (MMSE)

  from baseline to week 24 of treatment

• Changes in total score of RBANS

  from baseline to week 24 of treatment

• Change in the RBANS index score of immediate memory

  from baseline to week 24 of treatment

• Change in the RBANS index score of visuospatial/constructional

  from baseline to week 24 of treatment

• Change in the RBANS index score of language

  from baseline to week 24 of treatment

Study Arms (2)

active taVNS

EXPERIMENTAL

After disinfecting the stimulation sites (cymba conchae, cavum conchae, and earlobe), the auricular stimulation electrodes will be attached. For the active stimulation group, the actual functional electrodes delivering the current are positioned at the cymba conchae and cavum conchae. The stimulation parameters are set as follows:(1) Dense-disperse wave, with a stimulation frequency consisting of 20 Hz pulses for 10 seconds and 100 Hz pulses for 50 seconds per minute, and a pulse width of 0.2 ms ± 30%;(2) Stimulation intensity ranging from 4 to 6 mA, adjusted according to the individual patient's tolerance;(3) 30 minutes per session, twice daily;(4) 5 days per week, for 24 weeks.

Device: active transcutaneous auricular vagus nerve stimulation

sham taVNS

SHAM COMPARATOR

After disinfecting the stimulation sites (cymba conchae, cavum conchae, and earlobe), the auricular stimulation electrodes will be attached. For the sham stimulation group, the actual functional electrodes delivering the current are positioned at the earlobe. The stimulation parameters are set as follows:(1) Dense-disperse wave, with a stimulation frequency consisting of 20 Hz pulses for 10 seconds and 100 Hz pulses for 50 seconds per minute, and a pulse width of 0.2 ms ± 30%;(2) Stimulation intensity ranging from 4 to 6 mA, adjusted according to the individual patient's tolerance;(3) 30 minutes per session, twice daily;(4) 5 days per week, for 24 weeks.

Device: sham transcutaneous auricular vagus nerve stimulation

Interventions

sham transcutaneous auricular vagus nerve stimulation DEVICE

After disinfecting the stimulation sites (cymba conchae, cavum conchae, and earlobe), the auricular stimulation electrodes will be attached. For the sham stimulation group, the actual functional electrodes delivering the current are positioned at the earlobe. The stimulation parameters are set as follows:(1) Dense-disperse wave, with a stimulation frequency consisting of 20 Hz pulses for 10 seconds and 100 Hz pulses for 50 seconds per minute, and a pulse width of 0.2 ms ± 30%;(2) Stimulation intensity ranging from 4 to 6 mA, adjusted according to the individual patient's tolerance;(3) 30 minutes per session, twice daily;(4) 5 days per week, for 24 weeks.

sham taVNS

active transcutaneous auricular vagus nerve stimulation DEVICE

After disinfecting the stimulation sites (cymba conchae, cavum conchae, and earlobe), the auricular stimulation electrodes will be attached. For the active stimulation group, the actual functional electrodes delivering the current are positioned at the cymba conchae and cavum conchae. The stimulation parameters are set as follows:(1) Dense-disperse wave, with a stimulation frequency consisting of 20 Hz pulses for 10 seconds and 100 Hz pulses for 50 seconds per minute, and a pulse width of 0.2 ms ± 30%;(2) Stimulation intensity ranging from 4 to 6 mA, adjusted according to the individual patient's tolerance;(3) 30 minutes per session, twice daily;(4) 5 days per week, for 24 weeks.

active taVNS

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Type 2 diabetes mellitus
• Meets criteria for mild cognitive impairment
• Aged 40 to 75 years, with no gender restrictions
• HbA1c levels between 6.5% and 9.0%
• At least 6 years of formal education
• Able to cooperate with and complete all cognitive and functional assessments
• Right-handed
• Voluntary provision of written informed consent

You may not qualify if:

• Concomitant use of GLP-1 receptor agonists, Alzheimer's disease medications, anti-Parkinson's medications, antiepileptic drugs, or antipsychotic drugs within 3 months prior to screening
• Presence of dementia-related neurological disorders; current or history of clinically significant psychiatric disorders within the past 2 years (e.g., schizophrenia, bipolar disorder, major depressive disorder, generalized anxiety disorder, personality disorders)
• CNS diseases, including traumatic brain injury, intracranial hemorrhage, acute cerebral infarction, etc
• Severe sinusitis, nasal and sinus polyps, space-occupying lesions such as skull base or nasopharyngeal tumors; congenital diseases or history of trauma of the nose, maxillofacial region, or skull base that affect olfactory function; presence of upper respiratory tract infection symptoms (e.g., nasal congestion, rhinorrhea, fever) on the day of the MRI scan
• Acute complications of diabetes, including diabetic ketoacidosis, hyperglycemic hyperosmolar state, hypoglycemic coma, etc
• Severe impairment of major organ function (e.g., heart, liver, kidneys), including any of the following: ALT and/or AST \> 3×ULN. eGFR \< 45 mL/min/1.72 m² (CKD-EPI). History of unstable angina, myocardial infarction, or NYHA Class II or higher heart failure within 3 months prior to screening
• Concurrent major illnesses, such as active or untreated malignancies, or malignancies in clinical remission for less than 5 years.
• Contraindications for MRI scans (e.g., implanted metallic prostheses, claustrophobia); presence of cardiac pacemakers or other implantable medical devices; severe infection or ulceration of the auricular skin
• Pregnant or lactating women
• History of alcohol abuse, defined as an average weekly alcohol consumption exceeding 21 units for males and 14 units for females (1 unit = 360 mL of beer, 150 mL of wine, or 45 mL of distilled spirits/liquor)
• Any other conditions or factors that, in the opinion of the investigator, may confound the efficacy or safety evaluation of the study, making the participant unsuitable for enrollment

Sponsors & Collaborators

• The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School: lead

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Central Study Contacts

Jianguo Ruan, MD

CONTACT

86-25-83-106666; medrjg@163.com

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: PRINCIPAL INVESTIGATOR
• PI Title: associate chief physician

Study Record Dates

• First Submitted: May 19, 2026
• First Posted: June 11, 2026
• Study Start: May 20, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: June 11, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share