RYGB and the Gastric Adipose Axis

This study is enrolling participants by invitation only.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Naji Abumrad, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT01474785
First received: November 15, 2011
Last updated: February 21, 2014
Last verified: February 2014
  Purpose

The purpose of this study is to determine if interruption in gastric-adipose tissue axis signaling contributes to early improvements in oxidative stress, insulin sensitivity, and inflammation, and to determine if interruption of the stomach in RYGB results in reduction of plasma acylated ghrelin (AG) and in an altered acylated ghrelin:unacylated ghrelin (AG:UAG) ratio which may contribute to decreased oxidative stress and improved insulin sensitivity.


Condition Intervention
Obesity
Drug: Insulin
Drug: D-Glucose
Drug: Human ghrelin
Procedure: Adipose and muscle biopsies
Procedure: Adipose tissue microdialysis
Procedure: MRI
Procedure: MRS
Radiation: DXA
Procedure: Hyperinsulinemic-euglycemic clamp
Procedure: Blood draws
Other: Caloric restriction

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: RYGB Improves Metabolism by Interrupting the Gastric Adipose Tissue Axis

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Insulin sensitivity [ Time Frame: Pre- and post-operative or pre- and post-very low calorie diet ] [ Designated as safety issue: No ]

    Insulin sensitivity will be assessed using a one stage hyperinsulinemic-euglycemic clamp with stable isotope infusion.

    Effects of ghrelin infusion on insulin sensitivity will be assessed using a one stage hyperinsulinemic-euglycemic clamp.


  • Oxidative stress [ Time Frame: Pre- and post-operative or pre- and post-very low calorie diet ] [ Designated as safety issue: No ]
    Adipose tissue oxidative stress will be assessed in vivo using microdialysis of subcutaneous adipose tissue depots. Effects of ghrelin infusion on oxidative stress in adipose tissue will be assessed in vivo using microdialysis of subcutaneous adipose tissue depots.

  • Inflammation [ Time Frame: Pre- and post-operative or pre- and post-very low calorie diet ] [ Designated as safety issue: No ]
    Markers of inflammation (plasma CRP, TNF-alpha, IL-1, IL-6, IL-10) will be correlated with adipose tissue macrophage content and adipose tissue adipocytokine gene expression


Biospecimen Retention:   Samples With DNA

Whole blood, plasma, serum, microdialysate, muscle, fat.


Estimated Enrollment: 66
Study Start Date: January 2012
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Roux-en-Y gastric bypass surgery
Subjects scheduled for RYGB at Vanderbilt University Medical Center.
Drug: Insulin
80mU/m2/min IV infusion during hyperinsulinemic-euglycemic clamps (2/subject)
Drug: D-Glucose
[6,6,2H2] - Glucose: 22µmol/kg prime and 0.22µmol/kg-1-min-1 constant infusion during hyperinsulinemic-euglycemic clamps (2/subject)
Drug: Human ghrelin

Human Ghrelin

1pmol/kg.min 150 minutes per study (2 studies/RYGB subjects only)

Procedure: Adipose and muscle biopsies
Pre-op, intraoperatively, post-op. (Caloric restriction only group will have these procedures pre- and post-diet)
Procedure: Adipose tissue microdialysis
Pre-op, post-op Pre-diet, post-diet
Procedure: MRI
MRI-(Fat-Water Imaging)
Procedure: MRS
MRS-Characterization of tissue
Radiation: DXA
Pre-op, post-op Pre-diet, post-diet
Procedure: Hyperinsulinemic-euglycemic clamp
Pre-op, post-op Pre-diet, post-diet
Procedure: Blood draws
Pre-op, post-op Pre-diet, post-diet During RYGB and LAGB operations One time after discharge from hospital post-op and before second study visit Daily during week of caloric restriction (approximately 7 days)
Vertical Sleeve Gastrectomy
Subjects scheduled for vertical sleeve gastrectomy at Vanderbilt University Medical Center.
Drug: Insulin
80mU/m2/min IV infusion during hyperinsulinemic-euglycemic clamps (2/subject)
Drug: D-Glucose
[6,6,2H2] - Glucose: 22µmol/kg prime and 0.22µmol/kg-1-min-1 constant infusion during hyperinsulinemic-euglycemic clamps (2/subject)
Procedure: Adipose and muscle biopsies
Pre-op, intraoperatively, post-op. (Caloric restriction only group will have these procedures pre- and post-diet)
Procedure: Adipose tissue microdialysis
Pre-op, post-op Pre-diet, post-diet
Radiation: DXA
Pre-op, post-op Pre-diet, post-diet
Procedure: Hyperinsulinemic-euglycemic clamp
Pre-op, post-op Pre-diet, post-diet
Procedure: Blood draws
Pre-op, post-op Pre-diet, post-diet During RYGB and LAGB operations One time after discharge from hospital post-op and before second study visit Daily during week of caloric restriction (approximately 7 days)
Very low calorie diet
Subjects eligible for bariatric surgery at Vanderbilt University Medical Center
Drug: Insulin
80mU/m2/min IV infusion during hyperinsulinemic-euglycemic clamps (2/subject)
Drug: D-Glucose
[6,6,2H2] - Glucose: 22µmol/kg prime and 0.22µmol/kg-1-min-1 constant infusion during hyperinsulinemic-euglycemic clamps (2/subject)
Procedure: Adipose and muscle biopsies
Pre-op, intraoperatively, post-op. (Caloric restriction only group will have these procedures pre- and post-diet)
Procedure: Adipose tissue microdialysis
Pre-op, post-op Pre-diet, post-diet
Radiation: DXA
Pre-op, post-op Pre-diet, post-diet
Procedure: Hyperinsulinemic-euglycemic clamp
Pre-op, post-op Pre-diet, post-diet
Procedure: Blood draws
Pre-op, post-op Pre-diet, post-diet During RYGB and LAGB operations One time after discharge from hospital post-op and before second study visit Daily during week of caloric restriction (approximately 7 days)
Other: Caloric restriction
Caloric restriction group only (1 week)

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

We will study three obese cohorts prior to and within 7-10 days of the following procedures: RYGB, Vertical Sleeve Gastrectomy (VSG) with caloric restriction equivalent to the RYGB group, and a Caloric Restriction without surgery.

Criteria

Inclusion Criteria:

  • Age 18-65 years
  • BMI ≥ 35 kg/m2
  • Eligible for bariatric surgery

Exclusion Criteria:

  • Smoking >7 cigarettes per day
  • Precious malabsorptive or restrictive intestinal surgery
  • Pregnant or breastfeeding
  • Recent history of neoplasia (5<years ago)
  • Malabsorptive syndromes
  • Inflammatory intestinal disease
  • Established organ disfunction
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01474785

Locations
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 34232
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: Naji Abumrad, MD Vanderbilt University
Study Director: Robyn Tamboli, PhD Vanderbilt University
  More Information

No publications provided

Responsible Party: Naji Abumrad, Professor of Surgery, Chairman Department of Surgery, Vanderbilt University
ClinicalTrials.gov Identifier: NCT01474785     History of Changes
Other Study ID Numbers: #111237, R01DK091748
Study First Received: November 15, 2011
Last Updated: February 21, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Vanderbilt University:
Obesity
Bariatric surgery
Nashville, TN

Additional relevant MeSH terms:
Obesity
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms

ClinicalTrials.gov processed this record on August 28, 2014