RYGB and the Gastric Adipose Axis

This study is enrolling participants by invitation only.
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Naji Abumrad, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT01474785
First received: November 15, 2011
Last updated: March 30, 2016
Last verified: March 2016
  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. We will also determine if the altered nutrient exposure to the GI tract after bariatric surgery reveals a negative incretin effect of ghrelin.

Condition Intervention
Obesity
Drug: human ghrelin
Other: very low calorie diet

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

Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • change in glucose disposal rate [ Time Frame: baseline and 1 week ] [ Designated as safety issue: No ]
    Glucose disposal rate is a sensitive laboratory procedure for determining how your body uses sugar (called insulin sensitivity).


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
RYGB
Roux-en-Y gastric bypass surgery (RYGB) subjects
Drug: human ghrelin
1 pmol/kg/min of human ghrelin administered by IV two times
VSG
Vertical sleeve gastrectomy (VSG) subjects
Other: very low calorie diet
standard very low calorie diet that is prescribed for all RYGB patients after their operation
diet
Very low calorie diet prescribed for RYGB patients.
Other: very low calorie diet
standard very low calorie diet that is prescribed for all RYGB patients after their operation
Protocol II
Ghrelin infusion during a meal
Drug: human ghrelin
Other Name: 0.1 pmol/kg/min of human ghrelin administered by IV two to four times

  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

PROTOCOL I

Inclusion Criteria:

  • Age 18-65 years
  • BMI ≥ 35 kg/m^2
  • Scheduled for bariatric surgery
  • Considering bariatric surgery
  • Waiting for insurance approval for bariatric surgery
  • Currently not considering bariatric surgery, but otherwise eligible
  • Enrollment in medical weight loss program

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
  • Allergy to acetaminophen

PROTOCOL II

Inclusion Criteria:

  • BMI ≥ 35 kg/m^2
  • Age 21-65 years
  • Weight ≤ 200 kg

Exclusion Criteria:

  • Type 2 or Type 1 diabetes
  • Medications that alter insulin sensitivity or carbohydrate metabolism
  • Contraindication for nasal feeding tube (e.g., deviated septum, prior upper gastrointestinal bleed, or history of easy bleeding)
  • Positive pregnancy test
  • Known history of intestinal diseases including, but not limited to, inflammatory bowel disease (e.g. Chronic Ulcerative Colitis, Crohn's disease, celiac sprue)
  • Prior gastric or intestinal surgery or pancreas resection
  • History of cardiovascular disease, including but not limited to: myocardial infarction, angioplasty, arrhythmia, uncontrolled hypertension
  • History of chronic kidney disease or renal insufficiency; creatinine > 1.8 mg/dl.
  • History of chronic liver disease, including but not limited to: cirrhosis, hepatitis, portal hypertension; aspartate transaminase and/or alanine transaminase > 2x the upper limit of normal.
  • Abnormal electrocardiogram
  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
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
Principal Investigator: Naji Abumrad, MD Vanderbilt University
Study Director: Robyn Tamboli, PhD Vanderbilt University
  More Information

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: March 30, 2016
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on April 27, 2016