Cerebrospinal Fluid Biomarkers in Bariatric Surgery

Changes in Cerebrospinal Fluid Biomarkers After Bariatric Surgery

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.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Procedure: Roux-en-Y Gastric Bypass (RYGB); Procedure: Sleeve Gastrectomy (SG); Behavioral: Very Low Calorie Diet (VLCD)

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:

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

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

1. Before intervention
2. 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 Type: Interventional
• Enrollment (Actual): 51
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	Up to 12 months
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

Outcome Measure	Measure Description	Time Frame
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.	AgRP is neuropeptide that stimulates food intake and increases after diet-induced weight loss.	Up to 12 months
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

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Sharon L Wardlaw, MD, Columbia University

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2020
• Primary Completion (Actual): December 29, 2025
• Study Completion (Actual): December 29, 2025

Study Registration Dates

• First Submitted: April 15, 2020
• First Submitted That Met QC Criteria: April 16, 2020
• First Posted (Actual): April 17, 2020

Study Record Updates

• Last Update Posted (Actual): January 28, 2026
• Last Update Submitted That Met QC Criteria: January 26, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Obesity; Weight Loss; Bariatric Surgery; Sleeve Gastrectomy; Gastric Bypass; Low Calorie Diet
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Body Weight Changes; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Weight Loss; Therapeutics; Surgical Procedures, Operative; Digestive System Surgical Procedures; Anastomosis, Surgical; Bariatric Surgery; Bariatrics; Obesity Management; Gastroenterostomy; Gastric Bypass
• Other Study ID Numbers: AAAS8430; 1R01DK124465 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No