Physiologic and Functional Adaptations of Insulin Sensitive Tissues

NCT ID: NCT03407833

Last Updated: 2025-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ENROLLING_BY_INVITATION

Total Enrollment

500 participants

Study Classification

OBSERVATIONAL

Study Start Date

2018-02-13

Study Completion Date

2028-02-29

Brief Summary

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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.

Detailed Description

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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

Conditions

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

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

Surgical biopsy

Intervention Type 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).

Mixed-meal tolerance test

Intervention Type 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, 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.

Endoscopy biopsy

Intervention Type OTHER

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.

Endoscopy biopsy

Intervention Type OTHER

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.

Excised Liver Tissue Sampling

Intervention Type 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.

Interventions

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Endoscopy biopsy

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

Intervention Type OTHER

Surgical biopsy

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).

Intervention Type OTHER

Mixed-meal tolerance test

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.

Intervention Type OTHER

Excised Liver Tissue Sampling

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.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

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

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


* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Vanderbilt University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Charles R. Flynn

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Charles Flynn, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Locations

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Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

Countries

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United States

Other Identifiers

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171845

Identifier Type: -

Identifier Source: org_study_id