Vagal Nerve Stimulation and Glucose Metabolism

Obesity Clinical Trial

Official title:

The Effect of Vagal Nerve Stimulation on Enteroendocrine Secretion and Glucose Metabolism

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01117311
• Other study ID #: 09-008825
• Secondary ID: R01DK082396UL1RR
• Status: Completed
• Phase: N/A
• First received: May 4, 2010
• Last updated: November 14, 2013
• Start date: March 2011
• Est. completion date: November 2012

Study information

• Verified date: November 2013
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The overall aim of this application is to determine the mechanism(s) by which common bariatric surgical procedures alter carbohydrate metabolism. The study proposed will examine the effect of vagal nerve stimulation on insulin secretion and action.

Description:

The overall aim of this application is to determine the mechanism(s) by which common bariatric surgical procedures alter carbohydrate metabolism. Very often, resolution of diabetes occurs in the early post-operative period prior to the development of significant weight loss. It has been suggested that bariatric surgery alters insulin action but few studies have examined insulin secretion or postprandial glucose fluxes in such patients. At the present time, little is known about how the various bariatric surgical procedures alter glucose homeostasis. It is essential that the effect of bariatric surgery and meal size on these parameters be understood and accurately measured. Enteroendocrine secretion is affected by the rate of intestinal delivery of calories and may also be modulated by the enteric nervous system and the rate of direct delivery of nutrients to enteroendocrine cells. Direct measurement of intestinal transit is also an important part of understanding how bariatric surgery alters intestinal secretion of hormones that may alter glucose metabolism. The Oral and C-peptide Minimal Models when applied to C-peptide, glucose and insulin concentrations after ingestion of a standard labeled mixed meal can accurately measure insulin secretion and action. Subsequently, the disposition index provides a measurement of the appropriateness of insulin secretion for the prevailing insulin action. When coupled with established triple-tracer methodology, a mixed meal can be used to measure fasting and postprandial glucose fluxes. Though the vagal trunks are preserved during bariatric surgery, gastric transection during the formation of a gastric pouch for Roux-en-Y gastric bypass (RYGB), or during the sleeve gastrectomy for the duodenal switch procedure, may denervate post-gastric organs including the pancreas and intestine. Reversible vagal block results in weight loss, decreased caloric intake, earlier satiation and reduced hunger. The effect of this form of vagal denervation on glycemic control is unclear. There is evidence that hepatic parasympathetic input regulates insulin action in rodents. Vagal afferents are also important in hepatoportal glucose sensing.

Subjects enrolled into the study would be on stable Vagal Nerve Stimulation Blocker (VNB) intervention in excess of 12 months, having taken part in prior observational study examining the long-term effects of vagal inhibition. All subjects will be studied three times after using a mixed meal. Participants will be admitted to the Mayo Clinic Clinical Research Unit at 17.00 hours the evening before the study. Following ingestion of a standardized low calorie mixed meal (400 Kcal: 55% carbohydrate, 30% fat, and 15% protein) subjects will fast overnight. During the experiment subjects will undergo a mixed meal study as outlined below (Lead-in Mixed Meal 1). On the day after study, subjects will be randomized to one of 2 interventions: either discontinue use of the VNB or continue its use. Subjects will then be restudied (Mixed Meal 2) the day after admission to the Clinical Research Unit at 17.00 hours on the 13th day after randomization. To determine the metabolic effects, if any, of starting VNB therapy, on the day after study, VNB use will be resumed or discontinued depending on prior activation or inactivation. Subjects will then be restudied (Mixed Meal 3) the day after admission to the Clinical Research Unit at 17.00 hours on the 13th day after completion of Mixed Meal 2. Following completion of the study, VNB use will be resumed in all subjects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: November 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 35 Years to 75 Years

Eligibility

Previous Implantation of a Vagal Nerve Stimulator for obesity as part of a prior study examining the effect of vagal nerve stimulator on obesity

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Gastric Emptying
• Obesity
• Type 2 Diabetes

Intervention

Device:
• VNB on
The implanted Vagal Nerve Blocker will be on at the time of study.
• VNB off
The implanted Vagal Nerve Blocker will be off at the time of study.

Locations

Country	Name	City	State
United States	Mayo Clinic in Rochester	Rochester	Minnesota

Sponsors (3)

Lead Sponsor	Collaborator
Mayo Clinic	National Center for Research Resources (NCRR), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disposition Index	Total Disposition Index (DI) is a calculated value which represents the ability of a person's pancreas to lower blood glucose. A higher number means the pancreas is better able to lower blood glucose and a lower number means the pancreas is less able to lower blood glucose.	baseline, 2 weeks	No
Secondary	Gastric Emptying Half-time	Gastric emptying half time is the time for half of the ingested solids or liquids to leave the stomach.	approximately 2 hours after radiolabeled meal is ingested	No