Physiologic and Functional Adaptations of Insulin Sensitive Tissues

October 30, 2023 updated by: Charles R. Flynn, Vanderbilt University Medical Center

Physiologic and Functional Adaptations of Insulin Sensitive Tissues After Bariatric Surgery

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.

Study Overview

Detailed Description

Upper endoscopy (subset)

  • Intestinal biopsies will be obtained during scheduled upper endoscopy from the mid-duodenum and/or proximal jejunum. In the case that a patient requires an upper endoscopy after metabolic and bariatric surgery, biopsies will be obtained from the mid-jejunum.
  • Blood will be collected from an IV placed in the arm used for administering anesthesia required for the indicated procedure.

Colonoscopy (subset)

  • Biopsies of the colon will be obtained during scheduled colonoscopy.
  • Blood will be collected from an IV placed in the arm used for administering anesthesia required for the indicated procedure.

Metabolic and bariatric surgery (subset)

  • During the metabolic and bariatric surgical procedures, biopsy of the jejunum, liver and omentum (visceral adipose) may be obtained. Biopsies of skeletal muscle and subcutaneous adipose will be taken at the sites of trocar placement for laparotomy.
  • Blood will be collected from an IV placed in the arm used for administering anesthesia required for the indicated procedure.
  • Feces will be self-collected by the patient using a provided culture swab specimen container or FOB card.

Liver transplantation (subset)

• Tissue will be collected from excised disease liver

Study Type

Observational

Enrollment (Estimated)

500

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

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.

Description

Inclusion Criteria:

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

Additional inclusion criteria for individuals scheduled for metabolic and bariatric surgery: Obese, ≥ 40 kg/m2 or ≥ 35 kg/m2 + one comorbidity (type 2 diabetes [fasting blood glucose ≥ 120 mg/dL; HbA1C ≥ 6.5%]; fatty liver disease, hypertension, cardiovascular disease, hyperlipidemia)

Additional inclusion criteria for individuals scheduled for liver transplantation: diagnosis of nonalcoholic liver disease or nonalcoholic steatohepatitis

Exclusion Criteria:

  • 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

Additional exclusion criteria for patients undergoing endoscopy/colonoscopy:

  • Recent history of malignancy (<5 years ago)
  • Previous lap band surgery
  • Established renal disease

Additional exclusion criteria for patients undergoing bariatric surgery:

  • Previous lap band, sleeve gastrectomy, or gastric bypass surgery
  • Recent history of malignancy (< 5 years ago)
  • Established organ dysfunction

Additional exclusion criteria for patients undergoing liver transplantation:

  • Previous lap band, sleeve gastrectomy, or gastric bypass surgery
  • Alpha 1 anti-trypsin disease, Wilson's disease, viral hepatitis, alcoholic liver disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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.
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).
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, 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.
Tissue samples will be collected from the jejunum, duodenum, and colon during the subject's standard of care procedure.
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.
Tissue samples will be collected from the jejunum, duodenum, and colon during the subject's standard of care procedure.
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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ability to establish organoid cultures
Time Frame: 12 months
Measure percent success rate of making organoid cultures from tissue biopsies
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Charles Flynn, Ph.D., Vanderbilt University Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 13, 2018

Primary Completion (Estimated)

February 1, 2028

Study Completion (Estimated)

February 1, 2028

Study Registration Dates

First Submitted

January 4, 2018

First Submitted That Met QC Criteria

January 15, 2018

First Posted (Actual)

January 23, 2018

Study Record Updates

Last Update Posted (Actual)

October 31, 2023

Last Update Submitted That Met QC Criteria

October 30, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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