Cerebrospinal Fluid Biomarkers in Bariatric Surgery

Sponsor

Columbia University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04350892

Collaborator

(none)

Enrollment

Location

Arms

62.4

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goal of this project is to understand why bariatric surgery is such an effective treatment for obesity with a focus on brain mechanisms. Cerebrospinal fluid (CSF) neuropeptide, hormone and protein levels will be measured as a surrogate for changes in brain activity in participants before and after bariatric surgery as compared with participants before and after diet-induced weight loss. The investigators are studying neuropeptides and hormones that are know to be involved with the regulation of appetite and body weight to determine if some of the changes that are expected to occur after diet-induced weight loss do not occur after bariatric surgery. In addition, proteomic analysis will be used to uncover new protein biomarkers that are unique to surgical weight loss. The results of these studies will help explain why bariatric surgery is so effective in achieving long-term weight loss. Understanding how the central nervous system responds to bariatric surgery could help the development of alternative nonsurgical therapies for obesity and its metabolic complications.

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

Detailed Description

Peripheral metabolic signals communicate levels of energy stores to the brain and elicit a host of neuronal responses that maintain energy balance; such regulatory mechanisms make it difficult to maintain diet-induced weight loss. The goal is to understand how these central regulatory mechanisms are circumvented following surgical alterations in the gut in subjects after Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (SG) compared to carefully matched diet- induced weight loss controls who achieve weight loss on a low calorie liquid diet. Surgery participants will be patients who have already chosen to have a bariatric surgery procedure with their doctor. Diet participants will be provided with the low calorie liquid diet for approximately 3 months and will be monitored weekly throughout the study.

Surgery participants will be studied at 3 time-points:

Before the intervention
After surgery at 10-15% weight loss
At 12 months after surgery

Low calorie diet participants will be studied at 2 time-points:

Before intervention
At 10-15% weight loss (approximately 12 weeks on the diet)

At each time-point subjects will have a lumbar puncture (spinal tap) for cerebrospinal fluid (CSF) sampling and blood will be collected in the fasting state and in response to a liquid meal challenge. Body weight, waist and hip circumference will be measured.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

48 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

CohortCohort

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Changes in Cerebrospinal Fluid Biomarkers After Bariatric Surgery

Actual Study Start Date :

Oct 20, 2020

Anticipated Primary Completion Date :

Jan 1, 2025

Anticipated Study Completion Date :

Jan 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Roux-en-Y Gastric Bypass Surgery	Procedure: Roux-en-Y Gastric Bypass (RYGB) This surgery is often called gastric bypass. It is a weight-loss surgery that involves creating a small stomach pouch and bypassing part of the small intestine. If you decide with your doctor to have gastric bypass, you can be enrolled on this arm of the study. A surgery date should be pending before the investigators screen you for the study. The study does not cover the cost of the Roux-en-Y gastric bypass.
Active Comparator: Sleeve Gastrectomy Surgery	Procedure: Sleeve Gastrectomy (SG) Sleeve gastrectomy, is a weight-loss surgery that involves removing about 80% of the stomach. If you decide with your doctor to have sleeve gastrectomy, you can be enrolled on this arm of the study. A surgery date should be pending before the investigators screen you for the study. The study does not cover the cost of the sleeve gastrectomy.
Active Comparator: Very Low Calorie Diet	Behavioral: Very Low Calorie Diet (VLCD) Weight loss with calorie restricted liquid diet. Participants will be placed on a 800 kcal/day diet for meal replacement (Optifast) provided by the investigator for 12 weeks. Participants will be monitored weekly by the study dietician and medical staff.

Arm

Intervention/Treatment

Active Comparator: Roux-en-Y Gastric Bypass Surgery

Procedure: Roux-en-Y Gastric Bypass (RYGB)

This surgery is often called gastric bypass. It is a weight-loss surgery that involves creating a small stomach pouch and bypassing part of the small intestine. If you decide with your doctor to have gastric bypass, you can be enrolled on this arm of the study. A surgery date should be pending before the investigators screen you for the study. The study does not cover the cost of the Roux-en-Y gastric bypass.

Active Comparator: Sleeve Gastrectomy Surgery

Procedure: Sleeve Gastrectomy (SG)

Sleeve gastrectomy, is a weight-loss surgery that involves removing about 80% of the stomach. If you decide with your doctor to have sleeve gastrectomy, you can be enrolled on this arm of the study. A surgery date should be pending before the investigators screen you for the study. The study does not cover the cost of the sleeve gastrectomy.

Active Comparator: Very Low Calorie Diet

Behavioral: Very Low Calorie Diet (VLCD)

Weight loss with calorie restricted liquid diet. Participants will be placed on a 800 kcal/day diet for meal replacement (Optifast) provided by the investigator for 12 weeks. Participants will be monitored weekly by the study dietician and medical staff.

Outcome Measures

Primary Outcome Measures

Change in the levels of cerebrospinal fluid (CSF) proopiomelanocortin (POMC) derived peptides (fmol/ml) that occur in subjects after diet induced weight loss compared to RYGB and SG. [Up to 12 months]
POMC plays a critical role in regulating energy balance and levels decrease in the hypothalamus after diet-induced weight loss; this may lead to weight regain after dieting.
Comparison of changes in the CSF proteome that occur after diet-induced weight-loss compared to RYGB and SG using unbiased proteomic analysis. [Up to 12 months]

Secondary Outcome Measures

Comparison of the changes in Agouti-related protein (AgRP) concentrations (fmol/ml) in CSF and plasma that occur in subjects after diet induced weight loss compared to RYGB and SG. [Up to 12 months]
AgRP is neuropeptide that stimulates food intake and increases after diet-induced weight loss.
Comparison of changes in CSF cortisol (ng/mL) that occur in subjects after diet induced weight loss compared to RYGB and SG. [Up to 12 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

18-65 years old
BMI 35-55

Exclusion Criteria:

No clinically significant medical conditions
No use of tobacco
No alcohol or drug abuse
No recent weight change (+/-5%) within prior 6 months
No medications that may affect body weight or blood glucose
No diabetes medications, beta-blockers, opiates or glucocorticoids
No pregnancy, breastfeeding, or planning to become pregnant during the study (diet group only)
No lactose intolerance