Obesity & Overweight
Conditions
Keywords
Obesity & Overweight, Transcutaneous Auricular Vagus Nerve Stimulation, Lifestyle Intervention, Non-responders
Brief summary
This single-center, randomized, single-blind, sham-controlled pilot study aims to evaluate the adjunctive effect of transcutaneous auricular vagus nerve stimulation (taVNS) in overweight/obese patients who show a poor weight loss response to lifestyle intervention. Participants who achieve no more than 5% weight loss after 12 weeks of lifestyle intervention will be randomized to receive either taVNS plus lifestyle intervention or sham stimulation plus lifestyle intervention for an additional 12 weeks. The primary objective is to compare the percent change in body weight from baseline between the two groups after 12 weeks of intervention. Secondary objectives include evaluation of changes in body composition and fat distribution, autonomic function, liver-related parameters, and glycemic and lipid-related metabolic parameters.
Detailed description
Obesity is a chronic metabolic disease with substantial health consequences, and lifestyle intervention remains the foundation of weight management. However, a considerable proportion of overweight or obese individuals fail to achieve clinically meaningful weight loss after structured lifestyle intervention. In this study, patients with poor response to lifestyle intervention are defined as those who have completed 12 weeks of lifestyle intervention with weight loss of 5% or less. Transcutaneous auricular vagus nerve stimulation (taVNS) is a noninvasive neuromodulation technique that stimulates the auricular branch of the vagus nerve and may improve autonomic balance, appetite regulation, and energy metabolism. This study is designed to investigate whether taVNS can enhance weight loss and improve metabolic outcomes when used as an adjunct to lifestyle intervention in overweight/obese patients with poor early response. A total of 24 participants will be enrolled at a single center and randomized in a 1:1 ratio to either the taVNS plus lifestyle intervention group or the sham stimulation plus lifestyle intervention group. The intervention period will last 12 weeks. All participants will receive standardized lifestyle guidance including dietary management and exercise management. Dietary intervention will be individualized based on basal metabolic rate measured by InBody and guided by the Dietary Guidelines for Chinese Residents, with an intended daily energy deficit of approximately 500 kcal. Exercise management will require at least 3 days of moderate-to-high intensity physical activity per week, with a total duration of at least 150 minutes, monitored by a wearable device. Participants in the active treatment group will receive taVNS applied to the left cymba conchae using an intermittent electrical stimulation pattern (15 seconds on, 5 seconds off), frequency of 20 Hz, pulse width of 0.2 ms, and intensity gradually increased to a tolerable mild tingling sensation, usually 1.0-2.5 mA. Stimulation will be administered twice daily for 30 minutes each time, 5 times per week, for 12 weeks. Participants in the control group will receive sham stimulation at the left tail of the helix, with the same stimulation schedule and device settings. Assessments will be performed at baseline and after 12 weeks of intervention, including anthropometric measurements, body composition analysis, autonomic function testing, laboratory testing, and evaluation of hepatic steatosis and fibrosis using FibroTouch and liver MRI. The primary endpoint is percent change in body weight from baseline at week 12. Secondary endpoints include changes in body composition and fat distribution, autonomic function, liver-related parameters, and glycemic and lipid-related metabolic parameters.
Interventions
DEVICEtranscutaneous auricular vagus nerve stimulation
Participants will receive active transcutaneous auricular vagus nerve stimulation in addition to lifestyle Intervention for 12 weeks. Active stimulation will be delivered to the left cymba conchae using an intermittent waveform (15 seconds on, 5 seconds off) at 20 Hz with a pulse width of 0.2 ms. Stimulation intensity will be titrated from 0 mA to a level that produces mild tingling without obvious discomfort, usually 1.0-2.5 mA. Stimulation will be administered twice daily for 30 minutes per session, 5 days per week, for 12 weeks.
DEVICESham
Participants will receive sham stimulation in addition to lifestyle Intervention for 12 weeks. Sham stimulation will be applied to the left tail of the helix using the same waveform parameters, stimulation intensity titration, and treatment schedule as the active group, namely twice daily for 30 minutes per session, 5 days per week, for 12 weeks.
Sponsors
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
Only participants are masked in this trial. Participants are randomly assigned to active taVNS plus lifestyle intervention or sham stimulation plus lifestyle intervention. To maintain masking, sham stimulation uses the same device, similar stimulation procedures, and the same treatment schedule as active stimulation, but is applied to a non-vagal auricular site (the left tail of the helix). Randomization codes are generated by an independent unblinded team and allocation is concealed using sealed, opaque envelopes. Emergency unblinding materials are prepared and securely retained.
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
1. Completed 12 weeks of lifestyle intervention treatment with ≤5% weight loss during the treatment period; 2. Completed 12 weeks of lifestyle intervention, with less than 1 month since completion, and achieved ≤5% weight loss during the intervention period; 3. Current body mass index (BMI) ≥28 kg/m², or BMI ≥24 kg/m² with at least one weight-related comorbidity (e.g., hypertension or fatty liver disease); 4. Willingness to provide written informed consent.
Exclusion criteria
1. Presence of diseases that may substantially affect body weight homeostasis, including Cushing's syndrome, uncontrolled thyroid disease (thyroid-stimulating hormone \>6.0 mIU/L or \<0.4 mIU/L), malignancy, or similar conditions; 2. Use within the past 3 months of medications that may significantly affect body weight, including glucocorticoids and antipsychotic agents; 3. Skin infection or damage involving the auricular area; 4. Women planning pregnancy in the near future; 5. Inability to complete the 12-week intervention period for practical reasons, such as frequent business travel or planned travel.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Body Weight From Baseline | Baseline, 4 weeks, 8 weeks, 12 weeks | Percent change in body weight from baseline to week 12 will be compared between the taVNS plus lifestyle intervention group and the sham stimulation plus lifestyle intervention group to evaluate the adjunctive effect of taVNS on weight reduction. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Waist Circumference | Baseline, ,Week 4, Week 8, Week 12 | Change in waist circumference from baseline to Week 4, Week 8, and Week 12 will be assessed using standardized Change in waist circumference from baseline to Week 4, Week 8, and Week 12 will be assessed using standardized anthropometric measurement. Change in waist circumference from baseline to Week 4, Week 8, and Week 12 will be assessed using standardized anthropometric measurement. |
| Change in Body Composition and Fat Distribution | Baseline, ,Week 4, Week 8, Week 12 | Changes in body composition and fat distribution will be assessed by body fat percentage using anthropometric measurements and body composition analysis |
| Change in Visceral Fat Area | Baseline, ,Week 4, Week 8, Week 12 | Change in visceral fat area from baseline to Week 4, Week 8, and Week 12 will be assessed using body composition analysis. |
| Change in blood glucose | Baseline, Week 12 | Change in fasting blood glucose from baseline to Week 12 will be assessed using laboratory testing. |
| Change in Glycated Hemoglobin | Baseline, Week 12 | Change in glycated hemoglobin (HbA1c) from baseline to Week 12 will be assessed using laboratory testing. |
| Change in Hip Circumference | Baseline, ,Week 4, Week 8, Week 12 | Change in hip circumference from baseline to Week 4, Week 8, and Week 12 will be assessed using standardized anthropometric measurement. |
| Change in High-Density Lipoprotein Cholesterol | Baseline, Week 12 | Change in high-density lipoprotein cholesterol (HDL-C) from baseline to Week 12 will be assessed using laboratory testing. |
| Change in Low-Density Lipoprotein Cholesterol | Baseline, Week 12 | Change in low-density lipoprotein cholesterol (LDL-C) from baseline to Week 12 will be assessed using laboratory testing. |
| Change in Triglycerides | Baseline, Week 12 | Change in triglycerides from baseline to Week 12 will be assessed using laboratory testing. |
| Change in Insulin Resistance | Baseline, Week 12 | Change in insulin resistance from baseline to Week 12 will be assessed using the homeostatic model assessment of insulin resistance (HOMA-IR), calculated from fasting glucose and fasting insulin levels. |
| Change in Controlled Attenuation Parameter | Baseline, Week 12 | Change in controlled attenuation parameter (CAP) from baseline to Week 12 will be assessed using transient elastography. |
| Change in Liver Stiffness Measurement | Baseline, Week 12 | Change in liver stiffness measurement (LSM) from baseline to Week 12 will be assessed using transient elastography. |
| Change in Liver Function | Baseline, Week 12 | Change in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) from baseline to Week 12 will be assessed using laboratory testing. |
| Change in Heart Rate Variability | Baseline, Week 12 | Change in heart rate variability from baseline to Week 12 will be assessed using time-domain and/or frequency-domain heart rate variability analysis. |
| Change in Cardiovascular Autonomic Reflex Test Result | Baseline, Week 12 | Change in cardiovascular autonomic reflex function from baseline to Week 12 will be assessed using standardized cardiovascular autonomic reflex testing. |
Countries
China
Contacts
CONTACTYan Bi, MD, PhD
CONTACTTian Wei Gu, MD, PhD
Outcome results
None listed