Mechanisms Underlying Predictors of Success From Obesity Surgery

NCT02697253 | Withdrawn Phase 2 DMC FDA Drug

• 3 other identifiers: GCO 15-1990R01DK108643AAAQ1904
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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. 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. 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. 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.

Conditions

Obesity

Keywords

Roux-en-Y Bariatric Surgery; Psychosocial Variables; Behavioral Variables; Weight Loss; Food Intake; GLP-1; Reinforcing Value of Food; Exendin 9-39

Outcome Measures

Primary Outcomes (1)

• Successful Weight Loss

  % Excess body weight lost

  2 years

Secondary Outcomes (3)

• Intake amount in grams consumed in a food intake capacity test

  2 years

• Fullness levels based on a rating scale after food intake capacity test

  2 years

• Sickness levels based on a rating scale after food intake capacity test

  2 years

Study Arms (4)

Successful drug

EXPERIMENTAL

Participants who have a % weight loss ≥35 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 80 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

Unsuccessful drug

EXPERIMENTAL

Participants who have a % weight loss of ≤25 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 80 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

Success placebo

PLACEBO COMPARATOR

Participants who have a % weight loss ≥35 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 80 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

Unsuccess placebo

PLACEBO COMPARATOR

Participants who have a % weight loss of ≤25 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 80 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

Interventions

Exendin 9-39 and Sitagliptin DRUG

Infusion of exendin 9-39 at the rate of 600 pmol/kg/min, infusion time 80 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.

Successful drug; Unsuccessful drug

Placebo DRUG

Infusion of 0.9% saline solution (placebo infusion) for 80 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.

Success placebo; Unsuccess placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• BMI \>35 kg/m2 BMI
• BMI \< 65 kg/m2
• Preparing to undergo Roux-en-Y gastric bypass or gastric sleeve (RYGB/GS) surgery at St. Luke-Roosevelt Hospital
• Within the 18-65 age range
• Blood pressure under \<160/100 mmHg
• Fasting triglyceride \<600 mg/dl
• No recent (last 6 months) history of cardiovascular disease.
• Prior history of angioplasty or coronary artery bypass surgery with a normal stress test will not be a contraindication.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• Icahn School of Medicine at Mount Sinai: lead

Study Sites (1)

Mount Sinai - Morningside

New York, New York, 10025, United States

Location

MeSH Terms

Conditions

Obesity; Weight Loss

Interventions

exendin (9-39); Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Body Weight Changes

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Study Officials

• Harry Kissileff, PhD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 23, 2016
• First Posted: March 3, 2016
• Study Start: January 1, 2016
• Primary Completion: July 29, 2021
• Study Completion: July 29, 2021
• Last Updated: November 15, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)