Bariatric Surgery and LDL Cholesterol

Study Overview
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Brief Summary
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Background: Observational studies have shown that gastric bypass is superior to sleeve gastrectomy in terms of LDL cholesterol improvement. If these results are confirmed in randomized controlled trials, pre-surgical LDL cholesterol status should be a point to consider in the surgical procedure election. Objective: The primary objective is to compare 1-year LDL cholesterol remission after gastric bypass and sleeve gastrectomy in morbid obese patients. Methods: Phase 3, uni-centric, randomized clinical trial, with intention-to-treat analysis to compare LDL cholesterol remission between gastric bypass and sleeve gastrectomy with a 12 months follow-up. The inclusion criteria will be patients aged between 18-60 years old with a body mass index ≥40 or ≥35 kg/m2 with a significant obesity related comorbidity and high LDL cholesterol levels. Patients will be evaluated preoperatively (2 months before surgery) and at 3, 6 and 12 months after bariatric surgery. Examinations will include routine blood chemistry, anthropometric measures, food intake recall, physical activity questionnaires,intima media thickness, fecal samples for microbiota examinations, fat tissue samples and serum samples for lipidomics and hormonal analyses.

Detailed Description
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In the preoperative period, patients will follow a standard nutritional intervention that includes 6 monthly group sessions focused on achieving changes in dietary habits and hence ease adaptation after surgery. In addition, lipid-lowering treatment will be adjusted and standardized following the Institut Català de la Salut clinical practice guidelines. Cholesterol-lowering drugs will be withdrawn immediately after the surgical intervention to asses LDL cholesterol remission during follow-up. After surgery, a standardized protocol will be followed for the two groups in relation to dietary recommendations and physical activity, as well as the initiation of lipid-lowering medication after the intervention, in order to avoid the bias that may arise due to an open study.

Official Title
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BASALTO (Bariatric Surgery and LDL Cholesterol) Trial

Conditions
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Bariatric Surgery

Intervention / Treatment
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* Procedure: Gastric bypass
* Procedure: Sleeve gastrectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index (BMI) ≥40 or BMI ≥35 kg/m2 with a significant obesity related comorbidities. Age 18 - 60 years. Previous successfully instituted and supervised but failed adequate diet and exercise program. Elevated LDL cholesterol defined as LDL cholesterol concentration >130 mg/dL or treatment with cholesterol-lowering drugs. Exclusion Criteria: BMI >60 kg/m2. Previous BS. Exclusion criteria for BS: Significant psychiatric disorder. Severe eating disorder, active alcohol or substance abuse. Contraindications for major abdominal surgery. Active gastric ulcer disease. Severe hepatic diseases. Pregnancy or breastfeeding. Cases in whom SG or GB are preferred: Severe symptomatic gastro esophageal reflux disease despite medication. Large hiatal hernia. Expected dense adhesions at the level of the small bowel. Need for endoscopic follow-up of the duodenum, history of inflammatory bowel disease. History of renal transplantation in which drug malabsorption can be caused with a GB. Cholesterol lowering drugs will be withdrawn immediately after the surgical intervention to asses LDL cholesterol remission during follow-up. Cases in whom perioperative statins withdrawn cannot be adequate will be excluded: Established cardiovascular disease or subclinical cardiovascular disease (atheroma plaque detection in carotid ultrasonography exam) in which LDL cholesterol objectives are more aggressive or statins can be prescribed independently of LDL cholesterol levels. LDL cholesterol >190 mg/dL or history of familial hypercholesterolemia.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Gastric bypass<br>Bariatric surgery by gastric bypass (GB) | Procedure: Gastric bypass<br>* The GB technique consists of a 150-cm antecolic Roux limb with a 25-mm circular pouch-jejunostomy and exclusion of 50 cm of the proximal jejunum.<br>|
| Experimental: Sleeve gastrectomy<br>Bariatric surgery by sleeve gastrectomy (SG) | Procedure: Sleeve gastrectomy<br>* The SG technique consists of a longitudinal resection of the stomach from the angle of His to approximately 5 cm proximal to the pylorus, using a 35 French bougie inserted along the lesser curvature.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LDL cholesterol remission 1 year after GB and SG | Postoperative LDL cholesterol <130 mg/dL without cholesterol-lowering drugs | At 12 months after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LDL cholesterol remission at 3 months after GB and SG | Postoperative LDL cholesterol <130 mg/dL without cholesterol-lowering drugs | At 3 months after surgery | 
| LDL cholesterol remission at 6 months after GB and SG | Postoperative LDL cholesterol <130 mg/dL without cholesterol-lowering drugs | At 6 months after surgery | 
| LDL cholesterol improvement postoperatively | In patients without preoperative cholesterol lowering drugs: Decrease ≥20% in LDL cholesterol concentration (mg/dL) without cholesterol-lowering drugs. In patients with preoperative cholesterol lowering drugs: Medication withdrawn and LDL cholesterol >130 mg/dL, or decrease ≥20% in LDL cholesterol concentration without medication withdrawn. | At 12 months after surgery | 
| Hypertriglyceridemia remission postoperatively | Triglyceride concentration <150 mg/dL without fibrates | 12 months after surgery | 
| Low HDL cholesterol remission postoperatively | HDL cholesterol concentration >50 mg/dL in women, or >40 mg/dL in men | 12 months after surgery | 
| Changes in LDL cholesterol concentration postoperatively | Variation of LDL cholesterol concentration (mg/dL) with respect to preoperative value | At 3 months after surgery | 
| Changes in LDL cholesterol concentration postoperatively | Variation of LDL cholesterol concentration (mg/dL) with respect to preoperative value | At 6 months after surgery | 
| Changes in LDL cholesterol concentration postoperatively | Variation of LDL cholesterol concentration (mg/dL) with respect to preoperative value | At 12 months after surgery | 
| Changes in total cholesterol during follow-up | Variation of total cholesterol concentration (mg/dL) with respect to preoperative value | At 3 months after surgery | 
| Changes in total cholesterol during follow-up | Variation of total cholesterol concentration (mg/dL) with respect to preoperative value | At 6 months after surgery | 
| Changes in total cholesterol during follow-up | Variation of total cholesterol concentration (mg/dL) with respect to preoperative value | At 12 months after surgery | 
| Changes in HDL cholesterol during follow-up | Variation of HDL cholesterol concentration (mg/dL) with respect to preoperative value | At 3 months after surgery | 
| Changes in HDL cholesterol during follow-up | Variation of HDL cholesterol concentration (mg/dL) with respect to preoperative value | At 6 months after surgery | 
| Changes in HDL cholesterol during follow-up | Variation of HDL cholesterol concentration (mg/dL) with respect to preoperative value | At 12 months after surgery | 
| Changes in triglycerides during follow-up | Variation of triglycerides concentration (mg/dL) with respect to preoperative value | At 3 months after surgery | 
| Changes in triglycerides during follow-up | Variation of triglycerides concentration (mg/dL) with respect to preoperative value | At 6 months after surgery | 
| Changes in triglycerides during follow-up | Variation of triglycerides concentration (mg/dL) with respect to preoperative value | At 12 months after surgery | 
| Changes in lipoprotein(a) during follow-up | Variation of lipoprotein(a) concentration (mg/dL) with respect to preoperative value | At 3 months after surgery | 
| Changes in lipoprotein(a) during follow-up | Variation of lipoprotein(a) concentration (mg/dL) with respect to preoperative value | At 6 months after surgery | 
| Changes in lipoprotein(a) during follow-up | Variation of lipoprotein(a) concentration (mg/dL) with respect to preoperative value | At 12 months after surgery | 
| Changes in lipoproteins particle size | Variation of LDL cholesterol particle size (nm) with respect to preoperative value | At 3 months postoperatively | 
| Changes in lipoproteins composition | Variation of LDL cholesterol particles concentration (nmol/L) with respect to preoperative value | At 3 months postoperatively | 
| Changes in lipoproteins particle size | Variation of LDL cholesterol particle size (nm) with respect to preoperative value | At 6 months postoperatively | 
| Changes in lipoproteins composition | Variation of LDL cholesterol particles concentration (nmol/L) with respect to preoperative value | At 6 months postoperatively | 
| Changes in lipoproteins particle size | Variation of LDL cholesterol particle size (nm) with respect to preoperative value | At 12 months postoperatively | 
| Changes in lipoproteins composition | Variation of LDL cholesterol particles concentration (nmol/L) with respect to preoperative value | At 12 months postoperatively | 
| Change in patients' estimated cardiovascular risk | Variation of REGICOR score (10-year estimated cardiovascular risk, %) with respect to preoperative value | At 3 months postoperatively | 
| Change in patients' estimated cardiovascular risk | Variation of REGICOR score (10-year estimated cardiovascular risk, %) with respect to preoperative value | At 6 months postoperatively | 
| Change in patients' estimated cardiovascular risk | Variation of REGICOR score (10-year estimated cardiovascular risk, %) with respect to preoperative value | At 12 months postoperatively | 
| Type 2 diabetes complete remission | Glycated hemoglobin [HbA1c] value <6.0% and fasting glucose level <100 mg/dL without diabetes medications | At 3 months postoperatively | 
| Type 2 diabetes complete remission | Glycated hemoglobin [HbA1c] value <6.0% and fasting glucose level <100 mg/dL without diabetes medications | At 6 months postoperatively | 
| Type 2 diabetes complete remission | Glycated hemoglobin [HbA1c] value <6.0% and fasting glucose level <100 mg/dL without diabetes medications | At 12 months postoperatively | 
| Type of mechanisms involved in the different LDL cholesterol remission rates after GB and SG | Different eligible types: Weight loss, changes in targeted lipidomics, changes in lipoproteins particles size and composition, changes in dietary habits and physical activity, modifications in gut microbiota, gene and protein expression in adipose tissue, changes in gut hormones | At 3 months postoperatively | 
| Type of mechanisms involved in the different LDL cholesterol remission rates after GB and SG | Different eligible types: Weight loss, changes in targeted lipidomics, changes in lipoproteins particles size and composition, changes in dietary habits and physical activity, modifications in gut microbiota, gene and protein expression in adipose tissue, changes in gut hormones | At 6 months postoperatively | 
| Type of mechanisms involved in the different LDL cholesterol remission rates after GB and SG | Different eligible types: Weight loss, changes in targeted lipidomics, changes in lipoproteins particles size and composition, changes in dietary habits and physical activity, modifications in gut microbiota, gene and protein expression in adipose tissue, changes in gut hormones | At 12 months postoperatively | 
| Changes in intima media thickness | Variation of mean intima-media thickness (IMT, in mm) measured ultrasonographically in the far wall of bilateral common carotid arteries with respect to preoperative value | At 12 months postoperatively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bariatric surgery, gastric bypass, sleeve gastrectomy, LDL cholesterol, morbid obesity