Effects of Transcutaneous Auricular Vagus Nerve Stimulation on Obesity and Insulin Resistance
2022년 4월 26일 업데이트: Harald Stauss, Burrell College of Osteopathic Medicine
Being overweight or obese has been associated with insulin resistance contributing to an increased risk for the development of type II diabetes.
Food intake, metabolic rate, and blood glucose levels are regulated by the autonomic nervous system, including the vagus nerve.
This study evaluates the hypothesis that non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) affects hormones that regulate food intake and blood glucose levels in a way that is consistent with reduced food intake and lower blood glucose levels.
The investigators further hypothesize that these effects of taVNS depend on body weight.
In a cross-over design generally healthy study participants will receive either taVNS or a sham intervention for 30 minutes on two separate study days.
The order of the intervention on the two study days will be randomized and the two study days are at least one week apart.
Based on body mass index (BMI) study participants are assigned to either a normal weight (BMI<25), overweight (BMI<30), or obese (BMI>30) group.
Capillary blood samples taken by finger prick before and after the intervention on each study day will be analyzed for blood glucose concentration and hormones that are linked to food intake and blood glucose levels.
In addition, autonomic function will be assessed by heart rate variability analysis of ECG recordings obtained before, during, and after the intervention on each study day.
연구 개요
상세 설명
Clinical studies and experimental studies in animals have demonstrated that cervical vagus nerve stimulation causes weight loss in obese patients and has profound effects on glucose homeostasis.
Furthermore, anorexic and antidiabetic effects have been reported in response to non-invasive transcutaneous auricular vagus nerve stimulation (taVNS).
Thus, non-invasive taVNS may potentially prevent insulin resistance in obesity.
The objective of this study is to investigate the acute effects of taVNS on hormones and adipokines linking obesity with insulin resistance in human subjects.
The hypothesis of this study is that acute application of taVNS elicits anti-diabetic effects through modulation of plasma levels of insulin, glucagon, C-peptide, GLP-1 (stimulates insulin and suppresses glucagon release), and GIP (gastric inhibitory polypeptide, stimulates insulin secretion).
Furthermore, the investigators hypothesize that taVNS elicits anorexic effects by modulating ghrelin and leptin plasma levels.
Finally the investigators hypothesize that taVNS may reduce the impact of obesity on insulin resistance by modulating PAI-1 (plasminogen activator inhibitor-1; increased in obesity and metabolic syndrome), resistin (adipose tissue secretory factor, suggested to link obesity with insulin resistance), vistatin (enriched in visceral fat and may stimulate the insulin receptor), adipsin (secreted from adipocytes; improves β-cell function), and adiponectin (secreted from adipose tissue; increases insulin sensitivity).
In normal weight (BMI<25, n=14), overweight (BMI<30, n=14), and obese (BMI>30, n=14) and otherwise healthy study participants blood glucose levels and plasma concentrations (finger prick blood sampling) of insulin, glucagon, C-peptide, GLP-1, GIP, ghrelin, leptin, PAI-1, resistin, vistatin (Bio-Plex kit 171A7001M), adipsin, and adiponectin (Bio-Plex kit 171A7002M) will be determined before and after 30 minutes of taVNS (EMS 7500, 10 Hz, 300ms, n=7 in each body weight group) or sham taVNS (control experiment, n=7 in each body weight group).
Before, during and after taVNS or sham taVNS autonomic function will be assessed by heart rate variability analysis from ECG recordings.
The investigators expect that the outcome of this study will demonstrate that taVNS lowers blood glucose levels and elicits hormone/adipokine responses consistent with anorexia and improved insulin resistance.
The investigators further hypothesize that these effects of taVNS will be more pronounced in obese compared to overweight and normal weight study participants.
연구 유형
중재적
등록 (실제)
30
단계
- 해당 없음
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
-
-
New Mexico
-
Las Cruces, New Mexico, 미국, 88001
- Burrell College of Osteopathic Medicine
-
-
참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
18년 이상 (성인, 고령자)
건강한 자원 봉사자를 받아들입니다
예
연구 대상 성별
모두
설명
Inclusion Criteria:
- Generally healthy
Exclusion Criteria:
- Age under 18 years
- Pregnancy
- Acute illnesses/fever
- Any medication that interferes with the autonomic nervous system (e.g., beta blockers)
- Any medication that interferes with glucose metabolism (e.g., antidiabetic drugs)
- Any medication that interferes with lipid metabolism (e.g., statins)
- Any medical conditions that interfere with the autonomic nervous system
- Type 1 or Type 2 diabetes
- Epilepsy
- Cardiac conditions, including arrhythmia
- Vestibulocochlear neuronitis or nerve damage (e.g., hearing loss or tinnitus)
- Skin irritation/inflammation at the stimulation site at the ear
- Current drug or alcohol abuse
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 기초 과학
- 할당: 무작위화되지 않음
- 중재 모델: 크로스오버 할당
- 마스킹: 하나의
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: Normal Weight
This arm consists of study participants with a body mass index (BMI) of less than 25.
These study participants will participate on two study days.
On one study day non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) and on the other study day a sham procedure will be performed.
Capillary blood samples (finger prick) will be obtained before and after the interventions on both study days.
The ECG will be recorded before, during, and after the intervention on both study days.
|
A bipolar clip electrode is attached to the auricle at the location of the cymba conchae.
Electrical stimulation (30 Hz stimulation frequency, 300 μs pulse width) is applied for 30 min.
The stimulation current is determined individually for each participant by slowly increasing the stimulation current until the participants feel a mild tingling sensation at the site of the electrode.
Then the current is gradually reduced until the tingling sensation disappears.
This current will then be used for taVNS.
A TENS 7000 or EMS 7500 device (510(k): K080661) is used.
다른 이름들:
A bipolar clip electrode is attached to the auricle at the location of the cymba conchae but no electrical current is applied to the electrode.
다른 이름들:
|
|
실험적: Overweight
This arm consists of study participants with a body mass index (BMI) of more than 25 but less than 30.
These study participants will participate on two study days.
On one study day non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) and on the other study day a sham procedure will be performed.
Capillary blood samples (finger prick) will be obtained before and after the interventions on both study days.
The ECG will be recorded before, during, and after the intervention on both study days.
|
A bipolar clip electrode is attached to the auricle at the location of the cymba conchae.
Electrical stimulation (30 Hz stimulation frequency, 300 μs pulse width) is applied for 30 min.
The stimulation current is determined individually for each participant by slowly increasing the stimulation current until the participants feel a mild tingling sensation at the site of the electrode.
Then the current is gradually reduced until the tingling sensation disappears.
This current will then be used for taVNS.
A TENS 7000 or EMS 7500 device (510(k): K080661) is used.
다른 이름들:
A bipolar clip electrode is attached to the auricle at the location of the cymba conchae but no electrical current is applied to the electrode.
다른 이름들:
|
|
실험적: Obese
This arm consists of study participants with a body mass index (BMI) of more than 30.
These study participants will participate on two study days.
On one study day non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) and on the other study day a sham procedure will be performed.
Capillary blood samples (finger prick) will be obtained before and after the interventions on both study days.
The ECG will be recorded before, during, and after the intervention on both study days.
|
A bipolar clip electrode is attached to the auricle at the location of the cymba conchae.
Electrical stimulation (30 Hz stimulation frequency, 300 μs pulse width) is applied for 30 min.
The stimulation current is determined individually for each participant by slowly increasing the stimulation current until the participants feel a mild tingling sensation at the site of the electrode.
Then the current is gradually reduced until the tingling sensation disappears.
This current will then be used for taVNS.
A TENS 7000 or EMS 7500 device (510(k): K080661) is used.
다른 이름들:
A bipolar clip electrode is attached to the auricle at the location of the cymba conchae but no electrical current is applied to the electrode.
다른 이름들:
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Change in Blood Glucose Concentration induced by taVNS
기간: During the taVNS intervention (30 min).
|
The blood glucose concentration is measured before and after application of taVNS from capillary blood samples obtained by finger prick.
The change in blood glucose concentration is determined as the difference in the two blood glucose concentrations (after taVNS minus before taVNS).
|
During the taVNS intervention (30 min).
|
|
Change in Blood Glucose Concentration induced by sham taVNS
기간: During the sham taVNS intervention (30 min).
|
The blood glucose concentration is measured before and after application of sham taVNS from capillary blood samples obtained by finger prick.
The change in blood glucose concentration is determined as the difference in the two blood glucose concentrations (after sham taVNS minus before sham taVNS).
|
During the sham taVNS intervention (30 min).
|
|
Change in Insulin Plasma Concentration induced by taVNS
기간: During the taVNS intervention (30 min).
|
Using capillary blood samples obtained by finger prick the insulin plasma concentration will be determined using a Bioplex assay.
The insulin plasma concentration will be determined before and after application of taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after taVNS minus before taVNS).
|
During the taVNS intervention (30 min).
|
|
Change in Insulin Plasma Concentration induced by sham taVNS
기간: During the taVNS intervention (30 min).
|
Using capillary blood samples obtained by finger prick the insulin plasma concentration will be determined using a Bioplex assay.
The insulin plasma concentration will be determined before and after application of sham taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after sham taVNS minus before sham taVNS).
|
During the taVNS intervention (30 min).
|
|
Change in Glucagon Plasma Concentration induced by taVNS
기간: During the taVNS intervention (30 min).
|
Using capillary blood samples obtained by finger prick the glucagon plasma concentration will be determined using a Bioplex assay.
The glucagon plasma concentration will be determined before and after application of taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after taVNS minus before taVNS).
|
During the taVNS intervention (30 min).
|
|
Change in Glucagon Plasma Concentration induced by sham taVNS
기간: During the taVNS intervention (30 min).
|
Using capillary blood samples obtained by finger prick the glucagon plasma concentration will be determined using a Bioplex assay.
The glucagon plasma concentration will be determined before and after application of sham taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after sham taVNS minus before sham taVNS).
|
During the taVNS intervention (30 min).
|
|
Change in C-Peptide Plasma Concentration induced by taVNS
기간: During the taVNS intervention (30 min).
|
Using capillary blood samples obtained by finger prick the C-peptide plasma concentration will be determined using a Bioplex assay.
The C-peptide plasma concentration will be determined before and after application of taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after taVNS minus before taVNS).
|
During the taVNS intervention (30 min).
|
|
Change in C-Peptide Plasma Concentration induced by sham taVNS
기간: During the taVNS intervention (30 min).
|
Using capillary blood samples obtained by finger prick the C-peptide plasma concentration will be determined using a Bioplex assay.
The C-peptide plasma concentration will be determined before and after application of sham taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after sham taVNS minus before sham taVNS).
|
During the taVNS intervention (30 min).
|
|
Change in GLP-1 Plasma Concentration induced by taVNS
기간: During the taVNS intervention (30 min).
|
Using capillary blood samples obtained by finger prick the GLP-1 plasma concentration will be determined using a Bioplex assay.
The GLP-1 plasma concentration will be determined before and after application of taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after taVNS minus before taVNS).
|
During the taVNS intervention (30 min).
|
|
Change in GLP-1 Plasma Concentration induced by sham taVNS
기간: During the taVNS intervention (30 min).
|
Using capillary blood samples obtained by finger prick the GLP-1 plasma concentration will be determined using a Bioplex assay.
The GLP-1 plasma concentration will be determined before and after application of sham taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after sham taVNS minus before sham taVNS).
|
During the taVNS intervention (30 min).
|
|
Change in GIP Plasma Concentration induced by taVNS
기간: During the taVNS intervention (30 min).
|
Using capillary blood samples obtained by finger prick the GIP plasma concentration will be determined using a Bioplex assay.
The GIP plasma concentration will be determined before and after application of taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after taVNS minus before taVNS).
|
During the taVNS intervention (30 min).
|
|
Change in GIP Plasma Concentration induced by sham taVNS
기간: During the taVNS intervention (30 min).
|
Using capillary blood samples obtained by finger prick the GIP plasma concentration will be determined using a Bioplex assay.
The GIP plasma concentration will be determined before and after application of sham taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after sham taVNS minus before sham taVNS).
|
During the taVNS intervention (30 min).
|
|
Change in Ghrelin Plasma Concentration induced by taVNS
기간: During the taVNS intervention (30 min).
|
Using capillary blood samples obtained by finger prick the ghrelin plasma concentration will be determined using a Bioplex assay.
The ghrelin plasma concentration will be determined before and after application of taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after taVNS minus before taVNS).
|
During the taVNS intervention (30 min).
|
|
Change in Ghrelin Plasma Concentration induced by sham taVNS
기간: During the taVNS intervention (30 min).
|
Using capillary blood samples obtained by finger prick the ghrelin plasma concentration will be determined using a Bioplex assay.
The ghrelin plasma concentration will be determined before and after application of sham taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after sham taVNS minus before sham taVNS).
|
During the taVNS intervention (30 min).
|
|
Change in Leptin Plasma Concentration induced by taVNS
기간: During the taVNS intervention (30 min).
|
Using capillary blood samples obtained by finger prick the leptin plasma concentration will be determined using a Bioplex assay.
The leptin plasma concentration will be determined before and after application of taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after taVNS minus before taVNS).
|
During the taVNS intervention (30 min).
|
|
Change in Leptin Plasma Concentration induced by sham taVNS
기간: During the taVNS intervention (30 min).
|
Using capillary blood samples obtained by finger prick the leptin plasma concentration will be determined using a Bioplex assay.
The leptin plasma concentration will be determined before and after application of sham taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after sham taVNS minus before sham taVNS).
|
During the taVNS intervention (30 min).
|
|
Change in PAI-1 Plasma Concentration induced by taVNS
기간: During the taVNS intervention (30 min).
|
Using capillary blood samples obtained by finger prick the PAI-1 plasma concentration will be determined using a Bioplex assay.
The PAI-1 plasma concentration will be determined before and after application of taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after taVNS minus before taVNS).
|
During the taVNS intervention (30 min).
|
|
Change in PAI-1 Plasma Concentration induced by sham taVNS
기간: During the taVNS intervention (30 min).
|
Using capillary blood samples obtained by finger prick the PAI-1 plasma concentration will be determined using a Bioplex assay.
The PAI-1 plasma concentration will be determined before and after application of sham taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after sham taVNS minus before sham taVNS).
|
During the taVNS intervention (30 min).
|
|
Change in Resistin Plasma Concentration induced by taVNS
기간: During the taVNS intervention (30 min).
|
Using capillary blood samples obtained by finger prick the resistin plasma concentration will be determined using a Bioplex assay.
The resistin plasma concentration will be determined before and after application of taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after taVNS minus before taVNS).
|
During the taVNS intervention (30 min).
|
|
Change in Resistin Plasma Concentration induced by sham taVNS
기간: During the taVNS intervention (30 min).
|
Using capillary blood samples obtained by finger prick the resistin plasma concentration will be determined using a Bioplex assay.
The resistin plasma concentration will be determined before and after application of sham taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after sham taVNS minus before sham taVNS).
|
During the taVNS intervention (30 min).
|
|
Change in Vistatin Plasma Concentration induced by taVNS
기간: During the taVNS intervention (30 min).
|
Using capillary blood samples obtained by finger prick the vistatin plasma concentration will be determined using a Bioplex assay.
The vistatin plasma concentration will be determined before and after application of taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after taVNS minus before taVNS).
|
During the taVNS intervention (30 min).
|
|
Change in Vistatin Plasma Concentration induced by sham taVNS
기간: During the taVNS intervention (30 min).
|
Using capillary blood samples obtained by finger prick the vistatin plasma concentration will be determined using a Bioplex assay.
The vistatin plasma concentration will be determined before and after application of sham taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after sham taVNS minus before sham taVNS).
|
During the taVNS intervention (30 min).
|
|
Change in Adipsin Plasma Concentration induced by taVNS
기간: During the taVNS intervention (30 min).
|
Using capillary blood samples obtained by finger prick the adipsin plasma concentration will be determined using a Bioplex assay.
The adipsin plasma concentration will be determined before and after application of taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after taVNS minus before taVNS).
|
During the taVNS intervention (30 min).
|
|
Change in Adipsin Plasma Concentration induced by sham taVNS
기간: During the taVNS intervention (30 min).
|
Using capillary blood samples obtained by finger prick the adipsin plasma concentration will be determined using a Bioplex assay.
The adipsin plasma concentration will be determined before and after application of sham taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after sham taVNS minus before sham taVNS).
|
During the taVNS intervention (30 min).
|
|
Change in Adiponectin Plasma Concentration induced by taVNS
기간: During the taVNS intervention (30 min).
|
Using capillary blood samples obtained by finger prick the adipsin plasma concentration will be determined using a Bioplex assay.
The adiponectin plasma concentration will be determined before and after application of taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after taVNS minus before taVNS).
|
During the taVNS intervention (30 min).
|
|
Change in Adiponectin Plasma Concentration induced by sham taVNS
기간: During the taVNS intervention (30 min).
|
Using capillary blood samples obtained by finger prick the adipsin plasma concentration will be determined using a Bioplex assay.
The adiponectin plasma concentration will be determined before and after application of sham taVNS and the change in plasma concentration will be determined as the difference in the plasma concentrations (after sham taVNS minus before sham taVNS).
|
During the taVNS intervention (30 min).
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Changes in Autonomic Function induced by taVNS
기간: During the taVNS intervention (30 min).
|
Autonomic function will be assessed by heart rate variability analysis of ECG recordings obtained before and after application of taVNS.
Changes in autonomic function will be determined by the difference in heart rate variability before and after taVNS (after taVNS minus before taVNS).
|
During the taVNS intervention (30 min).
|
|
Changes in Autonomic Function induced by sham taVNS
기간: During the sham taVNS intervention (30 min).
|
Autonomic function will be assessed by heart rate variability analysis of ECG recordings obtained before and after application of sham taVNS.
Changes in autonomic function will be determined by the difference in heart rate variability before and after sham taVNS (after sham taVNS minus before sham taVNS).
|
During the sham taVNS intervention (30 min).
|
공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작 (실제)
2021년 6월 14일
기본 완료 (실제)
2022년 4월 26일
연구 완료 (실제)
2022년 4월 26일
연구 등록 날짜
최초 제출
2021년 6월 2일
QC 기준을 충족하는 최초 제출
2021년 6월 11일
처음 게시됨 (실제)
2021년 6월 15일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2022년 4월 28일
QC 기준을 충족하는 마지막 업데이트 제출
2022년 4월 26일
마지막으로 확인됨
2022년 4월 1일
추가 정보
이 연구와 관련된 용어
키워드
기타 연구 ID 번호
- 0079_2021
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
아니요
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
아니
미국 FDA 규제 기기 제품 연구
예
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .