Clinical trial NCT04350892: Cerebrospinal Fluid Biomarkers in Bariatric Surgery
Official title: Changes in Cerebrospinal Fluid Biomarkers After Bariatric Surgery
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Obesity
Keywords: Obesity
Bariatric Surgery
Gastric Bypass
Sleeve Gastrectomy
Weight Loss
Low Calorie Diet
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2020-04-17
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Cohort
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: Up to 12 months
measure: Comparison of changes in the CSF proteome that occur after diet-induced weight-loss compared to RYGB and SG using unbiased proteomic analysis.
timeFrame: Up to 12 months
Secondary outcomes:
measure: 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.
timeFrame: Up to 12 months
measure: Comparison of changes in CSF cortisol (ng/mL) that occur in subjects after diet induced weight loss compared to RYGB and SG.
timeFrame: Up to 12 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
Study officials:
affiliation: Columbia University
name: Sharon L Wardlaw, MD
role: PRINCIPAL_INVESTIGATOR
References: