Clinical trial NCT05230628: Auricular Vagus Stimulation in Obesity
Official title: The Effectiveness of Transcutaneous Electrical Nerve Stimulation of the Auricular Branch of the Vagus Nerve in Loss Weight and Improving the Quality of Life in Patients With Obesity
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Vagus Nerve Stimulation
Obesity
Keywords: auricular stimulation
auricular vagus nerve stimulation
blinding (masking)
transcutaneous vagus nerve stimulation (TENS)
vagus nerve stimulation (VNS)
obesity abdominal
nutrition disorders
overweight
body weight
active TENS
sham TENS
heart rate
total fat
body mass index
waist circumference
hip circumference
Heart rate variability
quality of life
Lead sponsor: National Medical Research Center for Therapy and Preventive Medicine
Sponsor class: OTHER_GOV
Collaborators: name: Moscow State University of Medicine and Dentistry
First posted: 2022-02-09
Enrollment: 131
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Model: 1:1 randomization of active stimulation vs. no stimulation for 6 months post randomization.
Primary purpose: TREATMENT

Brief summary: Transcutaneous vagus nerve stimulation (TENS) involves stimulation of the left and/or right auricular branch of the vagus nerve with low-frequency electrical impulses. In recent years, the possibilities of using this technology in chronic conditions characterized by immune and metabolic dysregulation have been studied. The aim of this study is to investigate the effectiveness of TENS in reducing weight and improving quality of life in patients with various degrees of obesity.

Detailed description: Obesity is one of the leading causes of disability and death worldwide. In 2016, more than 1.9 billion adults were overweight, according to the World Health Organization. According to current projections, by 2030, 60% of the world's population (that is, 3.3 billion people) may be overweight (2.2 billion) or obese (1.1 billion), if trends in obesity continue.

In 2021, the journal Nature Communications published data on the effectiveness of the use of an invasive device that stimulates the efferent fibers of the vagus nerve of the stomach with light fluxes and thereby reduces the severity of hunger. In addition, in small clinical trials in patients with depression and epilepsy treated with transcutaneous vagus nerve stimulation, this procedure has been shown to lead to significant weight loss.

Although the mechanisms are not fully understood, it is believed that a high-calorie diet contributes to the desensitization of the vagus afferent fibers to peripheral signals and leads to a decrease in the constitutive expression of orexigenic receptors and neuropeptides. Violation of signal transmission along the afferent fibers of the vagus nerve may be sufficient for the development of hyperphagia and obesity, and stimulation of the vagus nerve, respectively, can be used in the treatment of these conditions. Recent discoveries revealed a new and important role of the vagus nerve within a physiological mechanism that utilizes afferent and efferent signaling in controlling cytokine levels and inflammation - the inflammatory reflex.

Afferent vagus nerve projections to the GI tract and the hepatic portal system play a major role in communicating alterations in peripheral metabolic homeostasis, including changes in cholecystokinin, lipids, leptin, insulin and glucose levels to the brain. In a reflex manner, efferent vagus nerve innervations of the heart, liver and pancreas provide cardio-metabolic regulatory output. Cholecystokinin- and leptin-induced afferent vagus nerve activity importantly mediates satiety and regulates feeding behavior. Cholecystokinin, released as a result of intestinal lipid accumulation also causes activation of afferent signaling and subsequent efferent vagus nerve output to liver that suppresses hepatic gluconeogenesis.

Transcutaneous vagus nerve stimulation (TENS) involves the stimulation of the left and/or right auricular branch of the vagus nerve in the area of the cymba concha with low-frequency electrical impulses. The auricular branch of the vagus nerve runs superficially, which makes it a favorable target for non-invasive stimulation techniques to modulate vagal activity. It gained popularity due to minimal side effects and low cost.

In recent years, the use of this technology in the treatment of various disorders, including headache, tinnitus, prosocial behavior, atrial fibrillation, associative memory, schizophrenia, traumatic pain, and Crohn's disease, has been explored - chronic conditions characterized by immune and metabolic dysregulation. For this reason, there have been many early-stage clinical trials on a diverse range of conditions. These trials often report conflicting results for the same indication.

In this study, the investigators want to explore: will low-frequency transcutaneous electrical stimulation of the auricular branch of the vagus nerve contribute to weight loss in patients and improve their quality of life?

Eligibility criteria: Inclusion Criteria:

Adult patients with grade 1-2 nutritional obesity who are willing and able to give informed written consent to participate in the study, are on sinus rhythm and are not taking any antiarrhythmic drugs, including beta-blockers.

Exclusion Criteria:

* Cardiac arrhythmias: bradyarrhythmias, Atrioventricular blockades of any degree;
* Taking beta blockers;
* The endocrine nature of obesity;
* Expected technical difficulties when using the device on the part of the patient;
* Pregnant or plan on becoming pregnant or breastfeeding during the study period;
* Presence of an electrically, magnetically or mechanically activated implant, an intracerebral vascular clip, or any other electrically sensitive support system.

Primary outcomes:
measure: Percentage of body fat
timeFrame: 6-month follow-up
measure: Body Mass Index
timeFrame: 6-month follow-up
measure: Waist circumference
timeFrame: 6-month follow-up
Secondary outcomes:
measure: Total Weight Loss
timeFrame: 6-month follow-up
measure: Percentage of Total Weight Loss
timeFrame: 6-month follow-up
measure: Eating behavior questionnaire
timeFrame: 6-month follow-up
measure: Hip circumference
timeFrame: 6-month follow-up
measure: Waist circumference/Hip circumference
timeFrame: 6-month follow-up
measure: Lean Mass
timeFrame: 6-month follow-up
measure: Health-related Quality of Life
timeFrame: 6-month follow-up
measure: Adherence
timeFrame: 6-month follow-up
measure: Adverse Events
timeFrame: 6-month follow-up
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: National Medical Research Center for Therapy and Preventive Medicine
Study officials:
affiliation: National Medical Research Center for Therapy and Preventive Medicine
name: Oxana Drapkina
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kim WS, Hong S, Gamero M, Jeevakumar V, Smithhart CM, Price TJ, Palmiter RD, Campos C, Park SI. Organ-specific, multimodal, wireless optoelectronics for high-throughput phenotyping of peripheral neural pathways. Nat Commun. 2021 Jan 8;12(1):157. doi: 10.1038/s41467-020-20421-8.
citation: Verma N, Mudge JD, Kasole M, Chen RC, Blanz SL, Trevathan JK, Lovett EG, Williams JC, Ludwig KA. Auricular Vagus Neuromodulation-A Systematic Review on Quality of Evidence and Clinical Effects. Front Neurosci. 2021 Apr 30;15:664740. doi: 10.3389/fnins.2021.664740. eCollection 2021.
citation: Stavrakis S, Stoner JA, Humphrey MB, Morris L, Filiberti A, Reynolds JC, Elkholey K, Javed I, Twidale N, Riha P, Varahan S, Scherlag BJ, Jackman WM, Dasari TW, Po SS. TREAT AF (Transcutaneous Electrical Vagus Nerve Stimulation to Suppress Atrial Fibrillation): A Randomized Clinical Trial. JACC Clin Electrophysiol. 2020 Mar;6(3):282-291. doi: 10.1016/j.jacep.2019.11.008. Epub 2020 Jan 29.
citation: Wolf V, Kuhnel A, Teckentrup V, Koenig J, Kroemer NB. Does transcutaneous auricular vagus nerve stimulation affect vagally mediated heart rate variability? A living and interactive Bayesian meta-analysis. Psychophysiology. 2021 Nov;58(11):e13933. doi: 10.1111/psyp.13933. Epub 2021 Sep 2.
citation: Yap JYY, Keatch C, Lambert E, Woods W, Stoddart PR, Kameneva T. Critical Review of Transcutaneous Vagus Nerve Stimulation: Challenges for Translation to Clinical Practice. Front Neurosci. 2020 Apr 28;14:284. doi: 10.3389/fnins.2020.00284. eCollection 2020.