- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02815943
Postprandial Metabolism After Bariatric Surgery in Type 2 Diabetes (CB4)
May 16, 2022 updated by: André Carpentier, Université de Sherbrooke
Bariatric surgery procedures have now been firmly demonstrated to lead to significant improvement and even, in many cases, complete reversal of abnormal glucose homeostasis in type 2 diabetes (T2D).
Various surgery procedures are can be performed to induce weight loss.
The most striking anti-diabetic effects are observed with biliopancreatic diversion with duodenal switch (BPD-DS), followed by Roux-in-Y gastric bypass (RYGB) and sleeve gastrectomy (SG).
The first two procedures induce both a restriction of energy intake and a low absorption of dietary fatty acids while the latter exclusively targets energy intake restriction.
The investigator and others have shown that improvement of T2D occurs within days after BPD-DS or RYGB in the vast majority of patients, prior to any significant weight loss.
This very rapid metabolic recovery is explained by a normalization of β-cell function after meal challenges and ameliorated hepatic insulin sensitivity.
The investigator and others have shown that these acute anti-diabetic effects are mostly recapitulated by matched caloric restriction, independent of changes in gastrointestinal hormones, showing the importance of gastrointestinal-derived energy fluxes for acute diabetes control.
Muscle insulin sensitivity, on the other hand, improves more slowly in association with weight loss, demonstrating the heterogeneous metabolic response of the various organs to BPD-DS.
Some preliminary studies also demonstrate a rapid reduction of NEFA levels and production rate upon i.v.
administration of lipids during euglycemic hyperinsulinemic clamps.
This very rapid improvement in NEFA tolerance strongly suggests that adipose tissue storage of circulating fatty acids also improves very rapidly, prior to any significant weight loss, after BPD-DS.
It may also suggest an acceleration of oxidative fatty acid metabolism in organs such as the liver, the heart and/or skeletal muscles.
Studies of the rapid metabolic changes after bariatric surgery conducted thus far rapidly improved the understanding of the fundamental pathogenic defects of T2D.
However, much remains to be understood about the acute changes in gastrointestinal-derived metabolic fluxes, organ-specific metabolic responses to bariatric surgery and their relationship with the reversal of T2D.
Using in vivo methodological approaches, the investigator proposes to investigate the early organ-specific changes in dietary fatty acid metabolism in response to BPD-DS vs. SG and their relation to improved systemic changes in glucose homeostasis, insulin sensitivity and β-cell function in patients with T2D.
Study Overview
Status
Completed
Conditions
Detailed Description
Participants will undergo a metabolic study before and 8 to 12 days after bariatric surgery after a 12-hour fast and a three-day food and physical activity diary with accelerometry.
The patients recover very rapidly from the surgery and will be able to participate to the proposed investigations the week after their hospitalization on an outpatient basis on the earliest week day between 8 and 12 days after the surgery procedure.
The metabolic study is a 6-hour meal test using Positron Emitting Tomography (PET).
Study Type
Interventional
Enrollment (Actual)
18
Phase
- Not Applicable
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
-
-
Quebec
-
Sherbrooke, Quebec, Canada, J1H 5N4
- Centre de recherche du CHUS
-
-
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 to 65 years (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
Four groups of 11 subjects each: obese subjects with T2D or with normal glucose tolerance undergoing either BPD-DS or SG for treatment of obesity. T2D and control subjects will be matched for age (± 3 years), BMI (± 2 kg/m2) and gender across both BPD-DS and SG.
Exclusion Criteria:
- presence of overt cardiovascular disease, as assessed by history, physical exam, and abnormal EKG;
- treatment with a fibrate, a thiazolidinedione, a beta-blocker or other drugs known to affect lipid or carbohydrate metabolism (except statins, sulfonylurea, metformin, and other antihypertensive agents that can be temporarily stopped prior to the protocols);
- presence of liver or renal disease, uncontrolled thyroid disorder or other major illnesses;
- smoking (>1 cigarette/day) and/or consumption of more than 2 alcoholic beverages per day;
- prior history or current fasting plasma cholesterol level > 7 mmol/l or fasting TG > 6 mmol/l;
- any other contraindication to temporarily stop current medications for hyperglycemia, lipids, or hypertension.
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
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
OTHER: Before DBP-DS surgery
|
will be consumed over 30 minutes with [U-13C]-palmitate (0.2 g mixed in the liquid meal) and H2-glucose
a dynamic and whole body PET acquisition will be performed on a thoraco-abdominal segment, 150 minutes after an oral administration of 18FTHA
i.v.
administration of [7,7,8,8-2H]-palmitate (in 25% human albumin) from time -60 to 360 min.
will be performed every hour throughout the protocol along with exhaled breath collection
|
EXPERIMENTAL: After DBP-DS surgery
It is a bariatric surgery.
BPD consists in the exclusion of the duodenum from the alimentary tract with re-anastomosis of the blind loop 100 to 150 cm proximal to the ileo-coecal valve.
This leads to bypass of the biliopancreatic secretions towards the distal small intestine, resulting in fat malabsorption.
BPD also entails a distal gastrectomy to avoid the occurrence of peptic ulceration of the gastrointestinal anastomosis.
|
will be consumed over 30 minutes with [U-13C]-palmitate (0.2 g mixed in the liquid meal) and H2-glucose
a dynamic and whole body PET acquisition will be performed on a thoraco-abdominal segment, 150 minutes after an oral administration of 18FTHA
i.v.
administration of [7,7,8,8-2H]-palmitate (in 25% human albumin) from time -60 to 360 min.
will be performed every hour throughout the protocol along with exhaled breath collection
|
OTHER: Before SG surgery
|
will be consumed over 30 minutes with [U-13C]-palmitate (0.2 g mixed in the liquid meal) and H2-glucose
a dynamic and whole body PET acquisition will be performed on a thoraco-abdominal segment, 150 minutes after an oral administration of 18FTHA
i.v.
administration of [7,7,8,8-2H]-palmitate (in 25% human albumin) from time -60 to 360 min.
will be performed every hour throughout the protocol along with exhaled breath collection
|
EXPERIMENTAL: After SG surgery
It is a bariatric surgery where the stomach is reduced to about 15% of its original size, by surgical removal of a large portion of the stomach along the greater curvature.
|
will be consumed over 30 minutes with [U-13C]-palmitate (0.2 g mixed in the liquid meal) and H2-glucose
a dynamic and whole body PET acquisition will be performed on a thoraco-abdominal segment, 150 minutes after an oral administration of 18FTHA
i.v.
administration of [7,7,8,8-2H]-palmitate (in 25% human albumin) from time -60 to 360 min.
will be performed every hour throughout the protocol along with exhaled breath collection
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
glucose metabolism
Time Frame: 2 years
|
will be determined using tracers of glucose
|
2 years
|
dietary fatty acid uptake
Time Frame: 2 years
|
assessed using PET/CT method with oral administration of 18FTHA
|
2 years
|
whole body inter-organ partitioning
Time Frame: 2 years
|
assessed using PET/CT method with oral administration of 18FTHA
|
2 years
|
lipid metabolism
Time Frame: 2 years
|
will be determined using tracers of fatty acids
|
2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Dietary fatty acid oxidation rate
Time Frame: 2 years
|
will be measured using breath 13CO2 enrichment
|
2 years
|
Total oxidation rate
Time Frame: 2 years
|
will be determined by indirect calorimetry
|
2 years
|
Hormonal responses
Time Frame: 2 years
|
will be determined using a multiplex assay system.
|
2 years
|
Insulin sensitivity
Time Frame: 2 years
|
will be determined using different standard methods, including the HOMA-IR
|
2 years
|
Insulin secretion index (ISI)
Time Frame: 2 years
|
will be assessed using deconvolution of plasma C-peptide with standard C-peptide kinetic parameters
|
2 years
|
habitual food intake
Time Frame: 2 years
|
with a 3-day food record,
|
2 years
|
physical activity
Time Frame: 2 years
|
with portable arm band accelerometry for 3 days prior to each metabolic study
|
2 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
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
August 1, 2015
Primary Completion (ACTUAL)
December 1, 2019
Study Completion (ACTUAL)
December 1, 2019
Study Registration Dates
First Submitted
June 23, 2016
First Submitted That Met QC Criteria
June 23, 2016
First Posted (ESTIMATE)
June 28, 2016
Study Record Updates
Last Update Posted (ACTUAL)
May 17, 2022
Last Update Submitted That Met QC Criteria
May 16, 2022
Last Verified
May 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2015-901, 14-176
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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