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

N/ANot Yet RecruitingNCT07642518

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School38 enrolled

Overview

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.

This study is a 24-week, single-center, randomized, double-blind, sham-controlled, parallel-group clinical trial aimed at investigating the potential disease-modifying effects of transcutaneous auricular vagus nerve stimulation (taVNS) on cognitive impairment in 38 patients with type 2 diabetes mellitus (T2DM) complicated by mild cognitive impairment. Participants will be randomly assigned in a 1:1 ratio to receive either active taVNS (stimulation frequency: 20 Hz pulses for 10 seconds and 100 Hz pulses for 50 seconds per minute; 30 minutes per session, twice daily) or sham stimulation for 5 days per week. All participants will continue to receive treatment based on their original glucose-lowering therapies. The primary objective of the study is to evaluate improvements in cognitive function, while secondary endpoints include structural and functional brain changes, metabolic improvements, neurodegenerative biomarkers, and safety outcomes. Participants will undergo comprehensive cognitive and metabolic assessments at baseline, followed by a safety visit at Week 12 to monitor adverse events, treatment adherence, and metabolic parameters. The comprehensive evaluation at Week 24 will include cognitive assessments, neuroimaging, and metabolic profiling. During the study period, investigators will conduct weekly follow-ups via telephone or WeChat, and participants will attend monthly in-clinic visits to complete examinations such as capillary blood glucose, blood pressure, and heart rate, as well as to be inquired about treatment adherence and adverse reactions. All rationales for decision-making and efficacy evaluations must be thoroughly documented.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Interventions

active transcutaneous auricular vagus nerve stimulationDEVICE

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.

sham transcutaneous auricular vagus nerve stimulationDEVICE

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.

Eligibility

Sex: ALLMin age: 40 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Type 2 diabetes mellitus 2. Meets criteria for mild cognitive impairment 3. Aged 40 to 75 years, with no gender restrictions 4. HbA1c levels between 6.5% and 9.0% 5. At least 6 years of formal education 6. Able to cooperate with and complete all cognitive and functional assessments 7. Right-handed 8. Voluntary provision of written informed consent Exclusion Criteria: 1. 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 2. 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) 3. CNS diseases, including traumatic brain injury, intracranial hemorrhage, acute cerebral infarction, etc 4. 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 5. Acute complications of diabetes, including diabetic ketoacidosis, hyperglycemic hyperosmolar state, hypoglycemic coma, etc 6. 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 7. Concurrent major illnesses, such as active or untreated malignancies, or malignancies in clinical remission for less than 5 years. 8. 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 9. Pregnant or lactating women 10. 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) 11. 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

Outcomes

Primary Outcomes

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.

Time frame: Baseline, and Week 24

Secondary Outcomes

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

The MMSE contains a total of 30 items that assess orientation, registration, attention and calculation, recall, and language, with a score range from 0 to 30. Generally, a higher MMSE score reflects a better cognitive function.