ObesityNCT02710370
Intestinal Metabolic Reprogramming as a Key Mechanism of Gastric Bypass in Humans
An observational study of Obesity and Diabetes Mellitus, Type 2, run by University of Pittsburgh at 1 site in United States.
Trial summary
The purpose of this research study is to determine how gastric bypass surgery effects metabolism in obesity and Type 2 Diabetes. One mechanism that has been investigated in animal models is change to the biology of the small intestine (Roux limb) and how glucose and other fuels are metabolized (or how the body digests… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Obesity, Diabetes Mellitus, Type 2, Endocrine System Diseases
- How many people
- 46 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2016to 31 Aug 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients who plan to undergo gastric bypass, with or without Type 2 Diabetes.
Who may be able to join
- Patients who elect to undergo gastric bypass surgery
- Standard bariatric surgery criteria (A BMI 35 to 40 kg/m2, with an obesity comorbid condition, OR BMI 40 kg/m2 or >).
Who cannot join
- Prior bariatric or foregut surgery
- Documented history of Type 1 Diabetes
- Poor overall general health
- Impaired mental status
- Drug and/or alcohol addiction
- Currently smoking
- Pregnant or plans to become pregnant
- Portal hypertension and/or cirrhosis
Trial locations and contacts
1 site in 1 country.
United States1 site
Magee-Womens Hospital of UPMC
Pittsburgh, Pennsylvania, 15213
About this study
The purpose of this research study is to determine how gastric bypass surgery effects metabolism in obesity and Type 2 Diabetes. One mechanism that has been investigated in animal models is change to the biology of the small intestine (Roux limb) and how glucose and other fuels are metabolized (or how the body digests and uses sugar and other fuels). This study will evaluate the role of the intestine in the beneficial metabolic effects of gastric bypass surgery. It specifically will examine whether the intestine increases its metabolism and its activity, and whether this results in an increase in fuel utilization. Thirty two (32) subjects will be recruited (18 with and 14 without Type 2 Diabetes). At the time of gastric bypass surgery, a small piece of intestine that is usually discarded will be collected. At three time points over the first year after surgery, intestinal samples will be obtained by endoscopy or insertion of a lighted flexible tube through the mouth. Blood samples will be taken at all time points, as well. All samples will undergo comprehensive metabolic analyses. Comparisons will be made between the two groups to understand the metabolic changes over time and if there are differences between the two groups.
Read the detailed description
Several studies have concluded that Roux-en-Y gastric bypass surgery (RYGBS) is the best current treatment option for obesity-related Type 2 Diabetes Mellitus (T2DM). The mechanisms underlying RYGBS-induced improvement in glycemic control remain unclear. Many investigators have advocated that this effect does not depend upon body weight loss, based on clinical observations that improvement in glucose homeostasis occurs early in the postoperative period, often prior to hospital discharge. Understanding the mechanisms underlying the metabolic effects of RYGBS will help to engineer ways to improve RYGB or to produce these effects without surgery.
This study will examine the concept of intestinal metabolic reprogramming as one of the key mechanisms of action for diabetes improvement following Roux-en-Y gastric bypass surgery (RYGBS) in humans. It is hypothesized that the reconfigured intestine is characterized by an increase in energetically expensive processes, such as structural remodeling, cytoskeletal reorganization, and cellular proliferation. To accommodate the increased bioenergetics demands, the intestinal epithelium increases its metabolic activity and reprograms its fuel utilization. Specifically, glucose, cholesterol and amino acid metabolism are all dramatically altered to increase anabolic pathways and generate building blocks for cellular growth and maintenance.
It has not previously been possible to test this hypothesis in humans as: A) the adaptive processes of the intestine in patients undergoing RYGBS have not been thoroughly characterized, B) it is not known whether the intestinal reprogramming appears early enough to explain the prompt improvement in glucose metabolism observed after RYGBS in humans, and C) the variability of the degree of intestinal metabolic adaptation, which could account for the variability in remission of T2DM, has not been studied. This study will perform a longitudinal, comprehensive metabolic analysis of the Roux limb in human subjects with and without T2DM undergoing RYGBS and determine the time course of the adaptive metabolic changes.
Eighteen (18) subjects with and fourteen (14) subjects without T2DM (total 32 subjects), who have been scheduled to undergo RYGBS as standard of care, will be recruited. For each enrolled subject, data collection will include an intestinal tissue sample (Roux limb tissue sampling from discarded tissue) at the time of RYGBS, from the mucosa of the jejunum, within 40 cm from the gastrojejunal anastomosis. Postoperatively, tissue sampling from the same area will be performed by an Upper GI endoscopy, at 1 month (±15 days), 6 months (±1 month) and 12 months (±2 months) after RYGBS. Tissue samples will be processed for histo-morphological examination and for RNA, protein and metabolomics analyses. A blood sample will be obtained at all time points and analyzed for metabolic biomarkers. Data analysis will include description and comparison of the morphological, gene protein and metabolite signatures of the intestinal (Roux limb) tissue and the blood biomarkers from each time point. Additionally, these outcome measures will be compared between the two groups (T2DM and Non-T2DM). Finally, a correlation of the intestinal adaptive changes with metabolic status, some eating behaviors, adverse symptomatology, and quality of life will be undertaken.
- Conditions
- Obesity, Diabetes Mellitus, Type 2, Endocrine System Diseases, Glucose Metabolism Disorders, Metabolic Diseases
- Keywords
- Bariatric Surgery, Gastric Bypass, Obesity/surgery, Endoscopy, Digestive System, Blood Glucose/metabolism, Diabetes Mellitus, Experimental/metabolism, Energy Metabolism, Glucose/metabolism, Jejunum/metabolism, Metabolomics, Gene Expression
- Medical subject headings
- Obesity, Diabetes Mellitus, Type 2, Endocrine System Diseases, Glucose Metabolism Disorders, Metabolic Diseases, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Controls | Patients who meet criteria for gastric bypass surgery, and do not have a documented history of Type 1 or Type 2 Diabetes. | |
| Participants with Type 2 Diabetes | Patients who meet criteria for gastric bypass surgery, and have a documented history of Type 2 Diabetes. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Description of intestinal morphology.
Histology and electron microscopy will be used to assess cellular architecture, brush border, cytoskeleton and junctions, and the size and shape of organelles.
Measured: Baseline, at time of operation
Description of intestinal morphology.
Histology and electron microscopy will be used to assess cellular architecture, brush border, cytoskeleton and junctions, and the size and shape of organelles.
Measured: 1 month after surgery.
Description of intestinal morphology.
Histology and electron microscopy will be used to assess cellular architecture, brush border, cytoskeleton and junctions, and the size and shape of organelles.
Measured: 6 months after surgery.
Description of intestinal morphology.
Histology and electron microscopy will be used to assess cellular architecture, brush border, cytoskeleton and junctions, and the size and shape of organelles.
Measured: 12 months after surgery.
Characterization of gene and protein expression of markers of cellular proliferation, cytoskeletal remodeling, and cellular machinery of glucose and cholesterol metabolic pathways.
Gene expression (RT-PCR) and protein expression (western blotting) for about 100 markers of cellular proliferation (e.g., cyclins, MKi67, PCNA), cytoskeletal remodeling (e.g., brush border enzymes and proteins), cellular machinery of glucose and cholesterol metabolic pathways (e.g., glucose transporters, enzymes of biochemical pathways).
Measured: Baseline, at time of operation.
Characterization of gene and protein expression of markers of cellular proliferation, cytoskeletal remodeling, and cellular machinery of glucose and cholesterol metabolic pathways.
Gene expression (RT-PCR) and protein expression (western blotting) for about 100 markers of cellular proliferation (e.g., cyclins, MKi67, PCNA), cytoskeletal remodeling (e.g., brush border enzymes and proteins), cellular machinery of glucose and cholesterol metabolic pathways (e.g., glucose transporters, enzymes of biochemical pathways).
Measured: 1 month after surgery.
Characterization of gene and protein expression of markers of cellular proliferation, cytoskeletal remodeling, and cellular machinery of glucose and cholesterol metabolic pathways.
Gene expression (RT-PCR) and protein expression (western blotting) for about 100 markers of cellular proliferation (e.g., cyclins, MKi67, PCNA), cytoskeletal remodeling (e.g., brush border enzymes and proteins), cellular machinery of glucose and cholesterol metabolic pathways (e.g., glucose transporters, enzymes of biochemical pathways).
Measured: 6 months after surgery.
Characterization of gene and protein expression of markers of cellular proliferation, cytoskeletal remodeling, and cellular machinery of glucose and cholesterol metabolic pathways.
Gene expression (RT-PCR) and protein expression (western blotting) for about 100 markers of cellular proliferation (e.g., cyclins, MKi67, PCNA), cytoskeletal remodeling (e.g., brush border enzymes and proteins), cellular machinery of glucose and cholesterol metabolic pathways (e.g., glucose transporters, enzymes of biochemical pathways).
Measured: 12 months after surgery.
Description of metabolite profile of the intestine and serum/plasma.
Metabolite profiling of the tissues and serum/plasma, using mass spectrometry techniques.
Measured: Baseline, at time of operation.
Description of metabolite profile of the intestine and serum/plasma.
Metabolite profiling of the tissues and serum/plasma, using mass spectrometry techniques.
Measured: 1 month after surgery.
Description of metabolite profile of the intestine and serum/plasma.
Metabolite profiling of the tissues and serum/plasma, using mass spectrometry techniques.
Measured: 6 months after surgery.
Description of metabolite profile of the intestine and serum/plasma.
Metabolite profiling of the tissues and serum/plasma, using mass spectrometry techniques.
Measured: 12 months after surgery.
Change from baseline (time of operation) in morphological signatures.
Measured: Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.
Change from baseline (time of operation) in gene and protein expression for markers of cellular proliferation, cytoskeletal remodeling, and cellular machinery of glucose and cholesterol metabolic pathways.
Measured: Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.
Change from baseline (time of operation) in metabolite profile.
Measured: Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.
Secondary outcomes (13)
Comparison of intestinal morphology signature between patients with and without diabetes.
Measured: Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.
Comparison of gene and protein expression profiles and levels of expression of markers of cellular proliferation, cytoskeletal remodeling, and cellular machinery of glucose and cholesterol metabolic pathways between patients with and without diabetes.
Measured: Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.
Comparison of metabolite profile between patients with and without diabetes.
Measured: Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.
Correlation of intestinal morphology signature with eating behaviors. Assessed by specific questionnaire.
Morphology as described in Primary Measures 1 - 4 correlated with eating behaviors as obtained and described by the Eating and Weight History Form (EWH).
Measured: Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.
Correlation of eating behaviors with gene and protein expression of markers of cellular proliferation, cytoskeletal remodeling, and cellular machinery of glucose and cholesterol metabolic pathways. Assessed by specific questionnaire.
Gene and protein expression of markers of cellular proliferation, cytoskeletal remodeling, and cellular machinery of glucose and cholesterol metabolic pathways as described in Primary Measures 5 - 8 correlated with eating behaviors as obtained and described by the Eating and Weight History Form (EWH).
Measured: Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.
Correlation of metabolite profile with eating behaviors. Assessed by specific questionnaire.
Intestinal and serum/plasma metabolite profiling as described in primary outcomes 9 - 12 correlated with eating behaviors as obtained and described by the Eating and Weight History Form (EWH).
Measured: Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.
Correlation of intestinal morphology signature with quality of life assessed by SF-36 Instrument.
Morphology as described in Primary Measures 1 - 4 correlated with quality of life as measured by the SF-36 Instrument (total and subscales).
Measured: Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.
Correlation of quality of life assessed by SF-36 Instrument with gene and protein expression for markers of cellular proliferation, cytoskeletal remodeling, and cellular machinery of glucose and cholesterol metabolic pathways.
Gene and protein expression of markers of cellular proliferation, cytoskeletal remodeling, and cellular machinery of glucose and cholesterol metabolic pathways as described in Primary Measures 5 - 8 correlated with quality of life as measured by the SF-36 Instrument (total and subscales).
Measured: Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.
Correlation of metabolite profile with quality of life assessed by SF-36 Instrument.
Intestinal and serum/plasma metabolite profiling as described in primary outcomes 9 - 12 correlated with quality of life as measured by the SF-36 Instrument (total and subscales).
Measured: Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.
Correlation of intestinal morphology signature with adverse symptomatology (e.g., Dumping syndrome, Hypoglycemia). Assessed by specific questionnaires.
Morphology as described in Primary Measures 1 - 4 correlated with dumping syndrome characteristics as defined on the Sigstad Clinical Diagnostic Index and the Gastrointestinal and Neurological Symptom Form and hypoglycemic symptoms as described on the Glycemic Symptom Form.
Measured: Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.
Correlation of adverse symptomatology (Dumping syndrome, Hypoglycemia) with gene/protein expression of markers of cellular proliferation, cytoskeletal remodeling, and cellular machinery of glucose and cholesterol metabolic pathways.
Gene and protein expression levels of markers of cellular proliferation, cytoskeletal remodeling, and cellular machinery of glucose and cholesterol metabolic pathways as described in Primary Measures 5 - 8 correlated with dumping syndrome characteristics as defined on the Sigstad Clinical Diagnostic Index and the Gastrointestinal and Neurological Symptom Form and hypoglycemic symptoms as described on the Glycemic Symptom Form.
Measured: Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.
Correlation of metabolite profile with adverse symptomatology (e.g., Dumping syndrome, Hypoglycemia). Assessed by specific questionnaires.
Intestinal and serum/plasma metabolite profiling as described in primary outcomes 9 - 12 correlated with dumping syndrome characteristics as defined on the Sigstad Clinical Diagnostic Index and the Gastrointestinal and Neurological Symptom Form and hypoglycemic symptoms as described on the Glycemic Symptom Form.
Measured: Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.
Generation of intestinal organoids from Roux limb biopsies.
Feasibility of the generation of intestinal organoids for targeted mechanistic studies in vitro.
Measured: Baseline (0 months) and 1 month, 6 months and 12 months post-surgery. We began collection in August 2017 on some participants.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2016 (estimated)
- Study startFeb 2016
- Primary completion31 Aug 2028 (estimated)
- Study completion31 Aug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Collaborators
- Harvard University, National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Responsible party
- Principal investigator, Anita P. Courcoulas, University of Pittsburgh
- Investigators
- Anita Courcoulas, MD, MPH, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02710370
- Sponsor's protocol ID
- STUDY19060074
- Other IDs
- R01DK108642
- Status last verified
- Jun 2026
- First submitted
- 5 Feb 2016
- Last updated
- 11 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Saeidi N, Meoli L, Nestoridi E, Gupta NK, Kvas S, Kucharczyk J, Bonab AA, Fischman AJ, Yarmush ML, Stylopoulos N. Reprogramming of intestinal glucose metabolism and glycemic control in rats after gastric bypass. Science. 2013 Jul 26;341(6144):406-10. doi: 10.1126/science.1235103.
PubMed 23888041Laferrere B. Do we really know why diabetes remits after gastric bypass surgery? Endocrine. 2011 Oct;40(2):162-7. doi: 10.1007/s12020-011-9514-x. Epub 2011 Aug 19.
PubMed 21853297Courcoulas AP, Christian NJ, Belle SH, Berk PD, Flum DR, Garcia L, Horlick M, Kalarchian MA, King WC, Mitchell JE, Patterson EJ, Pender JR, Pomp A, Pories WJ, Thirlby RC, Yanovski SZ, Wolfe BM; Longitudinal Assessment of Bariatric Surgery (LABS) Consortium. Weight change and health outcomes at 3 years after bariatric surgery among individuals with severe obesity. JAMA. 2013 Dec 11;310(22):2416-25. doi: 10.1001/jama.2013.280928.
PubMed 24189773Stylopoulos N, Hoppin AG, Kaplan LM. Roux-en-Y gastric bypass enhances energy expenditure and extends lifespan in diet-induced obese rats. Obesity (Silver Spring). 2009 Oct;17(10):1839-47. doi: 10.1038/oby.2009.207. Epub 2009 Jun 25.
PubMed 19556976Arterburn DE, Courcoulas AP. Bariatric surgery for obesity and metabolic conditions in adults. BMJ. 2014 Aug 27;349:g3961. doi: 10.1136/bmj.g3961.
PubMed 25164369Nestoridi E, Kvas S, Kucharczyk J, Stylopoulos N. Resting energy expenditure and energetic cost of feeding are augmented after Roux-en-Y gastric bypass in obese mice. Endocrinology. 2012 May;153(5):2234-44. doi: 10.1210/en.2011-2041. Epub 2012 Mar 13.
PubMed 22416083Stefater-Richards MA, Panciotti C, Feldman HA, Gourash WF, Shirley E, Hutchinson JN, Golick L, Park SW, Courcoulas AP, Stylopoulos N. Gut adaptation after gastric bypass in humans reveals metabolically significant shift in fuel metabolism. Obesity (Silver Spring). 2023 Jan;31(1):49-61. doi: 10.1002/oby.23585.
PubMed 36541157Stefater-Richards MA, Panciotti C, Esteva V, Lerner M, Petty CR, Gourash WF, Courcoulas AP. Gastric bypass elicits persistent gut adaptation and unique diabetes remission-related metabolic gene regulation. Obesity (Silver Spring). 2024 Nov;32(11):2135-2148. doi: 10.1002/oby.24135. Epub 2024 Oct 15.
PubMed 39410706Courcoulas AP, Stefater MA, Shirley E, Gourash WF, Stylopoulos N. The Feasibility of Examining the Effects of Gastric Bypass Surgery on Intestinal Metabolism: Prospective, Longitudinal Mechanistic Clinical Trial. JMIR Res Protoc. 2019 Jan 24;8(1):e12459. doi: 10.2196/12459.
PubMed 30679147
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intestinal Metabolic Reprogramming as a Key Mechanism of Gastric Bypass in Humans
- ClinicalTrials.gov ID
- NCT02710370
- Acronym / sponsor ID
- STUDY19060074
- Conditions
- Obesity, Diabetes Mellitus, Type 2, Endocrine System Diseases, Glucose Metabolism Disorders, Metabolic Diseases
- Keywords
- Bariatric Surgery, Gastric Bypass, Obesity/surgery, Endoscopy, Digestive System, Blood Glucose/metabolism, Diabetes Mellitus, Experimental/metabolism, Energy Metabolism, Glucose/metabolism
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 46 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Collaborators
- Harvard University, National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Feb 2016
- Primary completion
- 31 Aug 2028 (estimated)
- Study completion
- 31 Aug 2028 (estimated)
- First posted
- 16 Mar 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research study is to determine how gastric bypass surgery effects metabolism in obesity and Type 2 Diabetes. One mechanism that has been investigated in animal models is change to the biology of the small intestine (Roux limb) and how glucose and other fuels are metabolized (or how the body digests and uses sugar and other fuels). This study will evaluate the role of the intestine in the beneficial metabolic effects of gastric bypass surgery. It specifically will examine whether the intestine increases its metabolism and its activity, and whether this results in an increase in fuel utilization. Thirty two (32) subjects will be recruited (18 with and 14 without Type 2 Diabetes). At the time of gastric bypass surgery, a small piece of intestine that is usually discarded will be collected. At three time points over the first year after surgery, intestinal samples will be obtained by endoscopy or insertion of a lighted flexible tube through the mouth. Blood samples will be taken at all time points, as well. All samples will undergo comprehensive metabolic analyses. Comparisons will be made between the two groups to understand the metabolic changes over time and if there are differences between the two groups.
Detailed description
Several studies have concluded that Roux-en-Y gastric bypass surgery (RYGBS) is the best current treatment option for obesity-related Type 2 Diabetes Mellitus (T2DM). The mechanisms underlying RYGBS-induced improvement in glycemic control remain unclear. Many investigators have advocated that this effect does not depend upon body weight loss, based on clinical observations that improvement in glucose homeostasis occurs early in the postoperative period, often prior to hospital discharge. Understanding the mechanisms underlying the metabolic effects of RYGBS will help to engineer ways to improve RYGB or to produce these effects without surgery.
This study will examine the concept of intestinal metabolic reprogramming as one of the key mechanisms of action for diabetes improvement following Roux-en-Y gastric bypass surgery (RYGBS) in humans. It is hypothesized that the reconfigured intestine is characterized by an increase in energetically expensive processes, such as structural remodeling, cytoskeletal reorganization, and cellular proliferation. To accommodate the increased bioenergetics demands, the intestinal epithelium increases its metabolic activity and reprograms its fuel utilization. Specifically, glucose, cholesterol and amino acid metabolism are all dramatically altered to increase anabolic pathways and generate building blocks for cellular growth and maintenance.
It has not previously been possible to test this hypothesis in humans as: A) the adaptive processes of the intestine in patients undergoing RYGBS have not been thoroughly characterized, B) it is not known whether the intestinal reprogramming appears early enough to explain the prompt improvement in glucose metabolism observed after RYGBS in humans, and C) the variability of the degree of intestinal metabolic adaptation, which could account for the variability in remission of T2DM, has not been studied. This study will perform a longitudinal, comprehensive metabolic analysis of the Roux limb in human subjects with and without T2DM undergoing RYGBS and determine the time course of the adaptive metabolic changes.
Eighteen (18) subjects with and fourteen (14) subjects without T2DM (total 32 subjects), who have been scheduled to undergo RYGBS as standard of care, will be recruited. For each enrolled subject, data collection will include an intestinal tissue sample (Roux limb tissue sampling from discarded tissue) at the time of RYGBS, from the mucosa of the jejunum, within 40 cm from the gastrojejunal anastomosis. Postoperatively, tissue sampling from the same area will be performed by an Upper GI endoscopy, at 1 month (±15 days), 6 months (±1 month) and 12 months (±2 months) after RYGBS. Tissue samples will be processed for histo-morphological examination and for RNA, protein and metabolomics analyses. A blood sample will be obtained at all time points and analyzed for metabolic biomarkers. Data analysis will include description and comparison of the morphological, gene protein and metabolite signatures of the intestinal (Roux limb) tissue and the blood biomarkers from each time point. Additionally, these outcome measures will be compared between the two groups (T2DM and Non-T2DM). Finally, a correlation of the intestinal adaptive changes with metabolic status, some eating behaviors, adverse symptomatology, and quality of life will be undertaken.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Controls | – | –Patients who meet criteria for gastric bypass surgery, and do not have a documented history of Type 1 or Type 2 Diabetes. |
| Participants with Type 2 Diabetes | – | –Patients who meet criteria for gastric bypass surgery, and have a documented history of Type 2 Diabetes. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients who plan to undergo gastric bypass, with or without Type 2 Diabetes.
Key inclusion criteria (2 listed)
- Patients who elect to undergo gastric bypass surgery
- Standard bariatric surgery criteria (A BMI 35 to 40 kg/m2, with an obesity comorbid condition, OR BMI 40 kg/m2 or >).
Key exclusion criteria (8 listed)
- Prior bariatric or foregut surgery
- Documented history of Type 1 Diabetes
- Poor overall general health
- Impaired mental status
- Drug and/or alcohol addiction
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Description of intestinal morphology.
Time frame: Baseline, at time of operation
Histology and electron microscopy will be used to assess cellular architecture, brush border, cytoskeleton and junctions, and the size and shape of organelles.
Description of intestinal morphology.
Time frame: 1 month after surgery.
Histology and electron microscopy will be used to assess cellular architecture, brush border, cytoskeleton and junctions, and the size and shape of organelles.
Description of intestinal morphology.
Time frame: 6 months after surgery.
Histology and electron microscopy will be used to assess cellular architecture, brush border, cytoskeleton and junctions, and the size and shape of organelles.
Description of intestinal morphology.
Time frame: 12 months after surgery.
Histology and electron microscopy will be used to assess cellular architecture, brush border, cytoskeleton and junctions, and the size and shape of organelles.
Characterization of gene and protein expression of markers of cellular proliferation, cytoskeletal remodeling, and cellular machinery of glucose and cholesterol metabolic pathways.
Time frame: Baseline, at time of operation.
Gene expression (RT-PCR) and protein expression (western blotting) for about 100 markers of cellular proliferation (e.g., cyclins, MKi67, PCNA), cytoskeletal remodeling (e.g., brush border enzymes and proteins), cellular machinery of glucose and cholesterol metabolic pathways (e.g., glucose transporters, enzymes of biochemical pathways).
Characterization of gene and protein expression of markers of cellular proliferation, cytoskeletal remodeling, and cellular machinery of glucose and cholesterol metabolic pathways.
Time frame: 1 month after surgery.
Gene expression (RT-PCR) and protein expression (western blotting) for about 100 markers of cellular proliferation (e.g., cyclins, MKi67, PCNA), cytoskeletal remodeling (e.g., brush border enzymes and proteins), cellular machinery of glucose and cholesterol metabolic pathways (e.g., glucose transporters, enzymes of biochemical pathways).
Characterization of gene and protein expression of markers of cellular proliferation, cytoskeletal remodeling, and cellular machinery of glucose and cholesterol metabolic pathways.
Time frame: 6 months after surgery.
Gene expression (RT-PCR) and protein expression (western blotting) for about 100 markers of cellular proliferation (e.g., cyclins, MKi67, PCNA), cytoskeletal remodeling (e.g., brush border enzymes and proteins), cellular machinery of glucose and cholesterol metabolic pathways (e.g., glucose transporters, enzymes of biochemical pathways).
Characterization of gene and protein expression of markers of cellular proliferation, cytoskeletal remodeling, and cellular machinery of glucose and cholesterol metabolic pathways.
Time frame: 12 months after surgery.
Gene expression (RT-PCR) and protein expression (western blotting) for about 100 markers of cellular proliferation (e.g., cyclins, MKi67, PCNA), cytoskeletal remodeling (e.g., brush border enzymes and proteins), cellular machinery of glucose and cholesterol metabolic pathways (e.g., glucose transporters, enzymes of biochemical pathways).
Description of metabolite profile of the intestine and serum/plasma.
Time frame: Baseline, at time of operation.
Metabolite profiling of the tissues and serum/plasma, using mass spectrometry techniques.
Description of metabolite profile of the intestine and serum/plasma.
Time frame: 1 month after surgery.
Metabolite profiling of the tissues and serum/plasma, using mass spectrometry techniques.
Description of metabolite profile of the intestine and serum/plasma.
Time frame: 6 months after surgery.
Metabolite profiling of the tissues and serum/plasma, using mass spectrometry techniques.
Description of metabolite profile of the intestine and serum/plasma.
Time frame: 12 months after surgery.
Metabolite profiling of the tissues and serum/plasma, using mass spectrometry techniques.
Change from baseline (time of operation) in morphological signatures.
Time frame: Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.
Change from baseline (time of operation) in gene and protein expression for markers of cellular proliferation, cytoskeletal remodeling, and cellular machinery of glucose and cholesterol metabolic pathways.
Time frame: Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.
Change from baseline (time of operation) in metabolite profile.
Time frame: Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.
13 secondary outcomes
Comparison of intestinal morphology signature between patients with and without diabetes.
Time frame: Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.
Comparison of gene and protein expression profiles and levels of expression of markers of cellular proliferation, cytoskeletal remodeling, and cellular machinery of glucose and cholesterol metabolic pathways between patients with and without diabetes.
Time frame: Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.
Comparison of metabolite profile between patients with and without diabetes.
Time frame: Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.
Correlation of intestinal morphology signature with eating behaviors. Assessed by specific questionnaire.
Time frame: Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.
Correlation of eating behaviors with gene and protein expression of markers of cellular proliferation, cytoskeletal remodeling, and cellular machinery of glucose and cholesterol metabolic pathways. Assessed by specific questionnaire.
Time frame: Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.
Correlation of metabolite profile with eating behaviors. Assessed by specific questionnaire.
Time frame: Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.
Correlation of intestinal morphology signature with quality of life assessed by SF-36 Instrument.
Time frame: Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.
Correlation of quality of life assessed by SF-36 Instrument with gene and protein expression for markers of cellular proliferation, cytoskeletal remodeling, and cellular machinery of glucose and cholesterol metabolic pathways.
Time frame: Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.
Correlation of metabolite profile with quality of life assessed by SF-36 Instrument.
Time frame: Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.
Correlation of intestinal morphology signature with adverse symptomatology (e.g., Dumping syndrome, Hypoglycemia). Assessed by specific questionnaires.
Time frame: Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.
Correlation of adverse symptomatology (Dumping syndrome, Hypoglycemia) with gene/protein expression of markers of cellular proliferation, cytoskeletal remodeling, and cellular machinery of glucose and cholesterol metabolic pathways.
Time frame: Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.
Correlation of metabolite profile with adverse symptomatology (e.g., Dumping syndrome, Hypoglycemia). Assessed by specific questionnaires.
Time frame: Baseline (0 months) and 1 month, 6 months and 12 months post-surgery.
Generation of intestinal organoids from Roux limb biopsies.
Time frame: Baseline (0 months) and 1 month, 6 months and 12 months post-surgery. We began collection in August 2017 on some participants.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2026.
- Background: PubMed 23888041Saeidi N, Meoli L, Nestoridi E, Gupta NK, Kvas S, Kucharczyk J, Bonab AA, Fischman AJ, Yarmush ML, Stylopoulos N. Reprogramming of intestinal glucose metabolism and glycemic control in rats after gastric bypass. Science. 2013 Jul 26;341(6144):406-10. doi: 10.1126/science.1235103.
- Background: PubMed 21853297Laferrere B. Do we really know why diabetes remits after gastric bypass surgery? Endocrine. 2011 Oct;40(2):162-7. doi: 10.1007/s12020-011-9514-x. Epub 2011 Aug 19.
- Background: PubMed 24189773Courcoulas AP, Christian NJ, Belle SH, Berk PD, Flum DR, Garcia L, Horlick M, Kalarchian MA, King WC, Mitchell JE, Patterson EJ, Pender JR, Pomp A, Pories WJ, Thirlby RC, Yanovski SZ, Wolfe BM; Longitudinal Assessment of Bariatric Surgery (LABS) Consortium. Weight change and health outcomes at 3 years after bariatric surgery among individuals with severe obesity. JAMA. 2013 Dec 11;310(22):2416-25. doi: 10.1001/jama.2013.280928.
- Background: PubMed 19556976Stylopoulos N, Hoppin AG, Kaplan LM. Roux-en-Y gastric bypass enhances energy expenditure and extends lifespan in diet-induced obese rats. Obesity (Silver Spring). 2009 Oct;17(10):1839-47. doi: 10.1038/oby.2009.207. Epub 2009 Jun 25.
- Background: PubMed 25164369Arterburn DE, Courcoulas AP. Bariatric surgery for obesity and metabolic conditions in adults. BMJ. 2014 Aug 27;349:g3961. doi: 10.1136/bmj.g3961.
- Background: PubMed 22416083Nestoridi E, Kvas S, Kucharczyk J, Stylopoulos N. Resting energy expenditure and energetic cost of feeding are augmented after Roux-en-Y gastric bypass in obese mice. Endocrinology. 2012 May;153(5):2234-44. doi: 10.1210/en.2011-2041. Epub 2012 Mar 13.
- Results publication: PubMed 36541157Stefater-Richards MA, Panciotti C, Feldman HA, Gourash WF, Shirley E, Hutchinson JN, Golick L, Park SW, Courcoulas AP, Stylopoulos N. Gut adaptation after gastric bypass in humans reveals metabolically significant shift in fuel metabolism. Obesity (Silver Spring). 2023 Jan;31(1):49-61. doi: 10.1002/oby.23585.
- Results publication: PubMed 39410706Stefater-Richards MA, Panciotti C, Esteva V, Lerner M, Petty CR, Gourash WF, Courcoulas AP. Gastric bypass elicits persistent gut adaptation and unique diabetes remission-related metabolic gene regulation. Obesity (Silver Spring). 2024 Nov;32(11):2135-2148. doi: 10.1002/oby.24135. Epub 2024 Oct 15.
- Results publication: PubMed 30679147Courcoulas AP, Stefater MA, Shirley E, Gourash WF, Stylopoulos N. The Feasibility of Examining the Effects of Gastric Bypass Surgery on Intestinal Metabolism: Prospective, Longitudinal Mechanistic Clinical Trial. JMIR Res Protoc. 2019 Jan 24;8(1):e12459. doi: 10.2196/12459.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anita Courcoulas, MD, MPH principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Obesity and Diabetes Mellitus, Type 2, run by University of Pittsburgh at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 11 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Description of intestinal morphology. (time frame: Baseline, at time of operation). The study lists 15 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02710370, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2026.