Metabolism and Bariatric Surgery Study

Sponsor

Columbia University (Other)

Overall Status

Recruiting

CT.gov ID

NCT03371368

Collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)

Enrollment

Location

Arms

68.4

Anticipated Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if diet-induced weight loss causes different changes in hormones that control appetite and glucose control than surgery-induced weight loss. The overall research plan is a non-randomized prospective study of 3 different weight loss (WL) interventions and a lean and an obese healthy control group.

Condition or Disease	Intervention/Treatment	Phase
Insulin Resistance Obesity	Procedure: Roux-en-Y Gastric Bypass (RYGBP) Procedure: Sleeve Gastrectomy (SG) Behavioral: Very Low Calorie Diet (VLCD)	N/A

Detailed Description

Weight loss (WL) improves obesity-related co-morbidities such as type 2 diabetes mellitus (DM). Unfortunately, WL through life-style interventions has a high degree of relapse and the lack of safe, effective and affordable therapies together with an increase in the prevalence of morbid obesity has led to a rise in bariatric procedures. Clinical trials in patients with DM show that improvements in glycemia vary between procedures and occur in the following order: Roux-en-Y gastric bypass (RYGB) > sleeve gastrectomy (SG) > laparoscopic adjustable gastric banding (LAGB) > medical/life-style therapy. This order mirrors the amount of WL with each intervention and is a major driver of glycemic improvement. The investigators have shown profound changes unique to RYGB and SG in levels of hormones that make up the "gut-brain" and "enteroinsular" axes. The association of some of these hormones with insulin sensitivity (IS) and glycemia, independent of WL strongly suggests that glycemic improvements after surgery occur in part through pathways that are distinct from just calorie restriction. This study builds on results showing that levels of fibroblast growth factor 19 (FGF19), a protein secreted by intestinal cells, are increased after RYGB and SG but not after low calorie diet (LCD). This difference may affect hormones that control the stress response to weight loss. The investigators will explore differences in hormones of the gut that affect appetite, body weight, and stress response in healthy lean and obese individuals. Obese individuals will also be studied before and after 15% body weight loss induced by LCD, RYGB or SG, and again at 1 year after study enrollment.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

75 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

CohortCohort

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Metabolic and Endocrine Effects of Bariatric Surgery

Actual Study Start Date :

Oct 16, 2017

Anticipated Primary Completion Date :

Jun 30, 2022

Anticipated Study Completion Date :

Jun 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Other: Gastric Bypass Diabetic and Non-diabetic Roux-en-Y gastric bypass surgery	Procedure: Roux-en-Y Gastric Bypass (RYGBP) This is a standard RYGBP procedure that would be performed clinically and is not research-specific. Other Names: RYGBP
Other: Sleeve Gastrectomy Diabetic and Non-diabetic sleeve gastrectomy surgery	Procedure: Sleeve Gastrectomy (SG) This is a standard SG procedure that would be performed clinically and is not research-specific. Other Names: SG
Active Comparator: Very Low Calorie Diet Diabetic and Non-diabetic very low calorie diet	Behavioral: Very Low Calorie Diet (VLCD) Weight loss with calorie restricted liquid diet. Subjects will be placed on a 800 kcal/day diet with a meal replacement (Optifast) provided by the investigator for 12 weeks. Then, transitioning to a higher calorie diet intake up to a year. Subjects will be closely monitored by study dietitian Other Names: VLCD
No Intervention: Obese Control Group Non-diabetic obese subjects
No Intervention: Lean Control Group Non-diabetic lean subjects

Outcome Measures

Primary Outcome Measures

Change in urine free cortisol level [Baseline and 1 year]
A linear mixed effects model will be used to compare the cortisol changes between the LCD and the surgery groups. Specifically, cortisol change will be modeled as longitudinal outcome, and the main predictors are time and treatment group, and the time-treatment interaction.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Men and women Ages 18-65 Years Old

Exclusion Criteria:

Altered Sleep-wake Cycle
Type 1 or 2 Diabetes
Previous Bariatric Surgery
Lactose Intolerance
Any Special Diet restrictions.
Use of medications that may affect body weight at screening or during a 3-month period prior.
Untreated thyroid disease
Other medical conditions like Cushing's, acromegaly, Hearth failure, Crohn's disease, etc.
Pregnancy
Tobacco or opioid use
Alcohol dependence
3% weight change over the 3month period prior to screening
Unwillingness to maintain current level of physical activity over duration of study period