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Mechanisms Underlying Predictors of Success From Obesity Surgery

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ClinicalTrials.gov Identifier: NCT02697253
Recruitment Status : Active, not recruiting
First Posted : March 3, 2016
Last Update Posted : December 13, 2018
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Ari Shechter, Columbia University

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Obesity Drug: Exendin 9-39 and Sitagliptin Drug: Placebo Phase 2

Detailed Description:
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

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: Mechanisms Underlying Predictors of Success From Obesity Surgery
Study Start Date : January 2016
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Sitagliptin

Arm Intervention/treatment
Experimental: Successful drug

Participants who have a % weight loss ≥35 at one-year post surgery and that either maintained or lost weight at 2 years post RYGB/SG surgery will be administered sitagliptin and receive infusion of Exendin 9-39 prior to an intake test.

Drug: Exendin 9-39 Infusion of exendin 9-39 at the rate of 600 pmol/kg/min, infusion time 90 minutes. An average of 18.2mg will be infused in a forearm vein during an oral glucose (30g) preload.

Drug: Sitagliptin 100mg tablet will be administered at 2200 hours the night before the visit. The day of the visit, the patient will take another 100mg tablet at 0700 hours.

Drug: Exendin 9-39 and Sitagliptin

Infusion of exendin 9-39 at the rate of 600 pmol/kg/min, infusion time 90 minutes. An average of 18.2mg will be infused in a forearm vein during an oral glucose (30g) preload.

100mg tablet will be administered at 2200 hours the night before the visit. The day of the visit, the patient will take another 100mg tablet at 0700 hours.


Experimental: Unsuccessful drug

Participants who have a % weight loss of ≤30 at one-year post surgery and that either maintained or gained weight at two years post RYGB/SG surgery will be administered Sitagliptin and receive infusion of Exendin 9-39 prior to an intake test.

Drug: Exendin 9-39 Infusion of exendin 9-39 at the rate of 600 pmol/kg/min, infusion time 90 minutes. An average of 18.2mg will be infused in a forearm vein during an oral glucose (30g) preload.

Drug: Sitagliptin 100mg tablet will be administered at 2200 hours the night before the visit. The day of the visit, the patient will take another 100mg tablet at 0700 hours.

Drug: Exendin 9-39 and Sitagliptin

Infusion of exendin 9-39 at the rate of 600 pmol/kg/min, infusion time 90 minutes. An average of 18.2mg will be infused in a forearm vein during an oral glucose (30g) preload.

100mg tablet will be administered at 2200 hours the night before the visit. The day of the visit, the patient will take another 100mg tablet at 0700 hours.


Placebo Comparator: Success placebo

Participants who have a % weight loss ≥35 at one-year post surgery and that either maintained or lost weight at 2 years post RYGB/SG surgery will be administered a placebo and receive a placebo infusion prior to an intake test.

Drug: Placebo Infusion of 0.9% saline solution (placebo infusion) for 60 minutes. An average of 18.2mg will be infused in a forearm vein during an oral glucose (30g) preload.

Drug: Placebo 100mg tablet will be administered at 2200 hours the night before the visit. The day of the visit, the patient will take another 100mg tablet at 0700 hours.

Drug: Placebo

Infusion of 0.9% saline solution (placebo infusion) for 60 minutes. An average of 18.2mg will be infused in a forearm vein during an oral glucose (30g) preload.

100mg Placebo tablet will be administered at 2200 hours the night before the visit. The day of the visit, the patient will take another 100mg placebo tablet at 0700 hours.


Placebo Comparator: Unsuccess placebo

Participants who have a % weight loss of ≤30 at one-year post surgery and that either maintained or gained weight at two years post RYGB/SG surgery will be administered a placebo and receive a placebo infusion prior to an intake test.

Drug: Placebo Infusion of 0.9% saline solution (placebo infusion) for 60 minutes. An average of 18.2mg will be infused in a forearm vein during an oral glucose (30g) preload.

Drug: Placebo 100mg tablet will be administered at 2200 hours the night before the visit. The day of the visit, the patient will take another 100mg tablet at 0700 hours.

Drug: Placebo

Infusion of 0.9% saline solution (placebo infusion) for 60 minutes. An average of 18.2mg will be infused in a forearm vein during an oral glucose (30g) preload.

100mg Placebo tablet will be administered at 2200 hours the night before the visit. The day of the visit, the patient will take another 100mg placebo tablet at 0700 hours.





Primary Outcome Measures :
  1. Successful Weight Loss [ Time Frame: 2 years ]
    % Excess body weight lost


Secondary Outcome Measures :
  1. Intake amount in grams consumed in a food intake capacity test [ Time Frame: 2 years ]
    Intake amount in grams consumed in a food intake capacity test

  2. Fullness levels based on a rating scale after food intake capacity test [ Time Frame: 2 years ]
    Fullness levels based on a rating scale after food intake capacity test

  3. Sickness levels based on a rating scale after food intake capacity test [ Time Frame: 2 years ]
    Sickness levels based on a rating scale after food intake capacity test



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02697253


Locations
United States, New York
Columbia University Medical Center - Russ Berrie Building
New York, New York, United States, 10032
Sponsors and Collaborators
Columbia University
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
Principal Investigator: Ari Shechter, PhD Columbia University

Responsible Party: Ari Shechter, Assistant Professor of Medical Sciences (in Medicine) at the Columbia University Medical Center, Columbia University
ClinicalTrials.gov Identifier: NCT02697253     History of Changes
Other Study ID Numbers: AAAQ1904
R01DK108643 ( U.S. NIH Grant/Contract )
First Posted: March 3, 2016    Key Record Dates
Last Update Posted: December 13, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Ari Shechter, Columbia University:
Roux-en-Y Bariatric Surgery
Psychosocial Variables
Behavioral Variables
Weight Loss
Food Intake
GLP-1
Reinforcing Value of Food
Exendin 9-39

Additional relevant MeSH terms:
Nutrition Disorders
Obesity
Overnutrition
Overweight
Body Weight
Signs and Symptoms
Sitagliptin Phosphate
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action