Mechanisms Underlying Predictors of Success From Obesity Surgery
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Obesity Weight Loss |
| Therapuetic Areas: | Endocrinology |
| Healthy: | No |
| Age Range: | 18 - 65 |
| Updated: | 12/15/2018 |
| Start Date: | January 2016 |
| End Date: | December 2020 |
The goal of this project is to identify predictors of success in the treatment of obesity
after bariatric surgery. The specific aims of this proposal are to:
1. Employ behavioral tests of mechanisms that control food intake in normal weight
individuals, to determine which intake control mechanisms lead to changes after
Roux-en-y gastric bypass (RYGB) or sleeve gastrectomy (SG); and
2. Measure behavioral and psycho-social predictors of weight loss and food intake
reduction, so as to determine which are most predictive of successful weight loss and
food intake reduction.
3. Account for success in reduction of food intake brought about by the pattern of hormone
release, particularly glucagon-like peptide-1 (GLP-1), Peptide YY (PYY) and gastric
distention, known to underlie satiation, coupled with post-ingestive changes in
reinforcing value of food and motivation to consume.
Tests of the hypothesis will be done by measuring responses to tasting, working for, and
consuming, foods on sensory, motivational, cognitive, and physiological variables, including
amount consumed and rate of eating under standardized conditions, before surgery and at a two
year follow up visit. In addition, the inhibitor sitagliptin will be administered the night
before and day of test meal and exendin-9-39 (EX9) will be infused before and during the meal
to determine whether blockade of GLP-1 / PYY receptors after surgery reverses intake
reduction. Investigators predict that successful patients will show changes that favor
reduction in food intake, rate of eating, motivation to consume, reward value of foods, and a
hormone profile that has been shown to generate satiation and maintain reduction in intake
(e.g. increased Cholecystokinin (CCK), GLP-1, PYY, reduced ghrelin). To the extent that
psycho-social and cognitive factors may override physiological brakes to eating behavior, the
subjects may fail to achieve success, and consequently the failure may be predicted from
over-impulsiveness or inability to suppress working for rewarding food stimuli. To test these
hypotheses, a total of 83 patients will be enrolled prior to RYGB/SG and restudied 2 years
after the surgery. The sitagliptin / EX9 studies will be done in a subset of 32 completers.
To test this aim, patients will be divided into 4 groups of 19. The 4 patients from each
group with the most weight loss (% weight loss ≥35 at one year post surgery and that either
maintained or lost weight at 2 years post-surgery, 16 patients in total) and least weight
loss (% weight loss of ≤30 at one year post surgery and that either maintained or gained
weight at two years 16 patients in total) will be recruited for these two additional
post-operative visits within 8 months of completing Visit #3 after the RYGB/SG surgery. A
total of 32 patients will be recruited for visits 4 and 5.
after bariatric surgery. The specific aims of this proposal are to:
1. Employ behavioral tests of mechanisms that control food intake in normal weight
individuals, to determine which intake control mechanisms lead to changes after
Roux-en-y gastric bypass (RYGB) or sleeve gastrectomy (SG); and
2. Measure behavioral and psycho-social predictors of weight loss and food intake
reduction, so as to determine which are most predictive of successful weight loss and
food intake reduction.
3. Account for success in reduction of food intake brought about by the pattern of hormone
release, particularly glucagon-like peptide-1 (GLP-1), Peptide YY (PYY) and gastric
distention, known to underlie satiation, coupled with post-ingestive changes in
reinforcing value of food and motivation to consume.
Tests of the hypothesis will be done by measuring responses to tasting, working for, and
consuming, foods on sensory, motivational, cognitive, and physiological variables, including
amount consumed and rate of eating under standardized conditions, before surgery and at a two
year follow up visit. In addition, the inhibitor sitagliptin will be administered the night
before and day of test meal and exendin-9-39 (EX9) will be infused before and during the meal
to determine whether blockade of GLP-1 / PYY receptors after surgery reverses intake
reduction. Investigators predict that successful patients will show changes that favor
reduction in food intake, rate of eating, motivation to consume, reward value of foods, and a
hormone profile that has been shown to generate satiation and maintain reduction in intake
(e.g. increased Cholecystokinin (CCK), GLP-1, PYY, reduced ghrelin). To the extent that
psycho-social and cognitive factors may override physiological brakes to eating behavior, the
subjects may fail to achieve success, and consequently the failure may be predicted from
over-impulsiveness or inability to suppress working for rewarding food stimuli. To test these
hypotheses, a total of 83 patients will be enrolled prior to RYGB/SG and restudied 2 years
after the surgery. The sitagliptin / EX9 studies will be done in a subset of 32 completers.
To test this aim, patients will be divided into 4 groups of 19. The 4 patients from each
group with the most weight loss (% weight loss ≥35 at one year post surgery and that either
maintained or lost weight at 2 years post-surgery, 16 patients in total) and least weight
loss (% weight loss of ≤30 at one year post surgery and that either maintained or gained
weight at two years 16 patients in total) will be recruited for these two additional
post-operative visits within 8 months of completing Visit #3 after the RYGB/SG surgery. A
total of 32 patients will be recruited for visits 4 and 5.
Obesity is a major public health as well as economic (expense of treating) problem
world-wide, and Roux-en-Y gastric bypass (RYGB) and Sleeve Gastrectomy (SG) surgeries are
effective treatments. A barrier to progress is that between 25% and 40% patients were not
successful in achieving and maintaining at least 30% weight loss, which is considered
medically successful for this operation. Understanding the mechanisms that contribute to
success or failure of this operation is an unsolved problem in obesity research, which this
proposal is addressing. The focus of this project is to identify mechanisms that contribute
to suppression of food intake following bariatric surgery, and to investigate whether these
mechanisms predict long-term success following bariatric surgery
world-wide, and Roux-en-Y gastric bypass (RYGB) and Sleeve Gastrectomy (SG) surgeries are
effective treatments. A barrier to progress is that between 25% and 40% patients were not
successful in achieving and maintaining at least 30% weight loss, which is considered
medically successful for this operation. Understanding the mechanisms that contribute to
success or failure of this operation is an unsolved problem in obesity research, which this
proposal is addressing. The focus of this project is to identify mechanisms that contribute
to suppression of food intake following bariatric surgery, and to investigate whether these
mechanisms predict long-term success following bariatric surgery
Inclusion Criteria:
- BMI greater than 35kg/m2
- BMI less than 65 kg/m2
- Preparing to undergo Roux-en-Y gastric bypass surgery at St. Luke-Roosevelt Hospital
- Within the 18-65 age range
Exclusion Criteria:
Diabetes Mellitus, active cancer; unstable angina; recent stroke; current therapy that may
affect glucose metabolism such as glucocorticoids, adrenergic agents; active infection;
kidney failure; severe liver dysfunction; heavy alcohol use; severe respiratory or cardiac
failure; pancreatitis; history of bullous pemphigoid, pregnancy and patients who are
currently or have had prior GLP-1 therapy. Patients with known hypersensitivity to Exendin
9-39 or similar products, albumin, sitagliptin and/or acetaminophen will also be excluded.
We found this trial at
1
site
New York, New York 10032
Phone: 212-851-5133
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