Physiologic and Functional Adaptations of Insulin Sensitive Tissues

NCT03407833 | Enrolling By Invitation

• 1 other identifier: 171845
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

The long-term goal is to understand the mechanisms of intestinal nutrient sensing and signal relays to insulin sensitive tissues (adipose, skeletal muscle, liver) in humans. The investigators hypothesize that human tissue biopsies (from obese surgery and non-surgery subjects as well as lean controls) can be used to understand the molecular mechanisms underlying intestinal nutrient sensing and signal relay in humans. The investigator will obtain tissue specimens from patients during scheduled upper endoscopies, colonoscopies and scheduled metabolic and bariatric surgeries or liver transplantation. A blood sample (4mL) will be obtained concurrent with these procedures. From metabolic and bariatric surgery subjects blood and tissues (liver, adipose, small intestine, omentum, skeletal muscle) can be collected at the time of surgery. From liver transplantation patients, excised liver tissue will be collected. Stool can be obtained preoperatively and at various time points after surgery. Some bariatric surgery subjects will participate in a mixed-meal tolerance test at their pre-operative visit and several post-operative visits to compare the whole-body metabolic alterations following bariatric procedures.

Conditions

Obesity; Bariatric Surgery Candidate; Roux-en-y Gastric Bypass; Liver Diseases; Diabetes; Insulin Resistance

Outcome Measures

Primary Outcomes (1)

• Ability to establish organoid cultures

  Measure percent success rate of making organoid cultures from tissue biopsies

  12 months

Study Arms (4)

Obese, surgery

Obese subjects recruited from the Center for Surgical Weight loss who are undergoing weight loss surgery as part of their standard of care. Tissue biopsies, blood, and fecal swabs will be collected at surgical visits.

Other: Surgical biopsy; Other: Mixed-meal tolerance test

Obese, nonsurgery

Obese subjects recruited from the Vanderbilt Endoscopy Clinic who are undergoing upper endoscopy or colonoscopy as part of their standard of care. Tissue biopsies, blood, and fecal swabs will be collected at day of procedure.

Other: Endoscopy biopsy

Lean control

Lean control subjects recruited from the Vanderbilt Endoscopy Clinic who are undergoing upper endoscopy or colonoscopy as part of their standard of care. Tissue biopsies, blood, and fecal swabs will be collected at day of procedure.

Other: Endoscopy biopsy

Liver transplant

Lean or obese subjects who are undergoing liver transplantation as part of their standard of care. Excised liver tissue will be collected the day of procedure.

Other: Excised Liver Tissue Sampling

Interventions

Endoscopy biopsy OTHER

Tissue samples will be collected from the jejunum, duodenum, and colon during the subject's standard of care procedure.

Lean control; Obese, nonsurgery

Surgical biopsy OTHER

Biopsy of the liver is standard of care for diagnosing NAFLD. Biopsy of omentum, skeletal muscle and subcutaneous adipose (the latter two tissues taken at the site of trocar placement) will be collected intraoperatively at the time of Roux-en-Y gastric bypass (RYGB) or vertical sleeve gastrectomy (VSG).

Obese, surgery

Mixed-meal tolerance test OTHER

The mixed meal tolerance test (MMTT) shows how much insulin your body is making after drinking a liquid meal beverage that contains fats, protein and carbohydrates (sugar). Glucose, C-peptide, free fatty acids, triglycerides, incretins, pancreatic polypertide, bile aceis, and fatty acid amides can also be measured. A total of 9 tablespoons of blood is taken over a 255 minute period.

Obese, surgery

Excised Liver Tissue Sampling OTHER

Tissue will be collected from the excised liver for research after the diseased liver has been removed as part of the standard of care procedure.

Liver transplant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Obese or lean subjects seen in the Vanderbilt Endoscopy Clinic, obese subjects planning surgery at the Center for Surgical Weight Loss, or obese or lean subjects planning liver transplantation surgery will be approached by research staff to participate in the study.

You may qualify if:

• \- Scheduled for upper endoscopy, colonoscopy or metabolic and bariatric surgery, or liver transplantation at Vanderbilt University Medical Center.

You may not qualify if:

• Known history of intestinal diseases including, but not limited to, inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease) and celiac sprue.
• Smoking \>7 cigarettes per day
• Malabsorptive syndromes
• Pregnant or breastfeeding
• Recent history of malignancy (\<5 years ago)
• Previous lap band surgery
• Established renal disease
• Previous lap band, sleeve gastrectomy, or gastric bypass surgery
• Recent history of malignancy (\< 5 years ago)
• Established organ dysfunction
• Previous lap band, sleeve gastrectomy, or gastric bypass surgery
• Alpha 1 anti-trypsin disease, Wilson's disease, viral hepatitis, alcoholic liver disease

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Biopsy tissue specimens will be stored in RNAlater© and will be used to measure mRNA expression profiles. Blood and fecal samples will also be obtained and stored.

MeSH Terms

Conditions

Diabetes Mellitus; Insulin Resistance; Obesity; Liver Diseases

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Digestive System Diseases

Study Officials

• Charles Flynn, Ph.D.

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 4, 2018
• First Posted: January 23, 2018
• Study Start: February 13, 2018
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028
• Last Updated: December 18, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)