Ursodeoxycholic acid for the prevention of symptomatic gallstone disease after bariatric surgery: study protocol for a randomized controlled trial (UPGRADE trial)

Abstract

BackgroundThe number of bariatric interventions for morbid obesity is increasing worldwide. Rapid weight loss is a major risk factor for gallstone development. Approximately 11 % of patients who underwent Roux-en-Y gastric bypass develop symptomatic gallstone disease. Gallstone disease can lead to severe complications and often requires hospitalization and surgery. Ursodeoxycholic acid (UDCA) prevents the formation of gallstones after bariatric surgery. However, randomized controlled trials with symptomatic gallstone disease as primary endpoint have not been conducted. Currently, major guidelines make no definite statement about postoperative UDCA prophylaxis and most bariatric centers do not prescribe UDCA.MethodsA randomized, placebo-controlled, double-blind multicenter trial will be performed for which 980 patients will be included. The study population consists of consecutive patients scheduled to undergo Roux-en-Y gastric bypass or sleeve gastrectomy in three bariatric centers in the Netherlands. Patients will undergo a preoperative ultrasound and randomization will be stratified for pre-existing gallstones and for type of surgery. The intervention group will receive UDCA 900 mg once daily for six months. The placebo group will receive similar-looking placebo tablets. The primary endpoint is symptomatic gallstone disease after 24 months, defined as admission or hospital visit for symptomatic gallstone disease. Secondary endpoints consist of the development of gallstones on ultrasound at 24 months, number of cholecystectomies, side-effects of UDCA and quality of life. Furthermore, cost-effectiveness, cost-utility and budget impact analyses will be performed.DiscussionThe UPGRADE trial will answer the question whether UDCA reduces the incidence of symptomatic gallstone disease after Roux-en-Y gastric bypass or sleeve gastrectomy. Furthermore it will determine if treatment with UDCA is cost-effective.Trial registrationNetherlands Trial Register (trialregister.nl) 6135. Date registered: 21-Nov-2016.

Clinical Practice Guidelines for the Perioperative Nutrition, Metabolic, and Nonsurgical Support of Patients Undergoing Bariatric Procedures – 2019 Update: Cosponsored by American Association of Clinical Endocrinologists/American College of Endocrinology, The Obesity Society, American Society for Metabolic and Bariatric Surgery, Obesity Medicine Association, and American Society of Anesthesiologists

“…A meta‐analysis of eight studies (retrospective, prospective cohort, and randomized controlled) with 816 patients by Magouliotis et al supported the role of 500 to 600 mg/day of ursodeoxycholic acid for 6 months after bariatric surgery. A more definitive, randomized, double‐blind multicenter trial (N = 900 patients with SG or RYGB) assessed the efficacy of 900 mg/day of ursodeoxycholic acid for 6 months on symptomatic gallstones by 24 months .…”

An Inverse Association of Weight and the Occurrence of Asymptomatic Gallbladder Stone Disease in Hypercholesterolemia Patients in Northwest China: A Case-Control Study.

“…We synthesize the relevant data with the following viewpoints: On the one hand, rapid weight loss leads to a change in cholesterol metabolism and consequently increases the concentration of cholesterol in the bile to a level at which not all cholesterol can be dissolved by bile salts. Undissolved cholesterol is prone to crystallize into stones, especially in the presence of calcium and mucin, a glycoprotein that stimulates cholesterol crystal aggregation (47). On the other hand, we consider lost weight to be a risk factor for GSD in patients with hypercholesterolemia, resulting from the participants including lean individuals, who may have diet models characterized by irrational vegetarian diets during weight loss.…”

An inverse association of weight and the occurrence of asymptomatic gallbladder stone disease in Hypercholesterolemia patients in northwest China: a case-control study.

“…We synthesize the relevant data with the following viewpoints: On the one hand, rapid weight loss leads to a change in cholesterol metabolism and consequently increases the concentration of cholesterol in the bile to a level at which not all cholesterol can be dissolved by bile salts. Undissolved cholesterol is prone to crystallize into stones, especially in the presence of calcium and mucin, a glycoprotein that stimulates cholesterol crystal aggregation [50]. On the other hand, we consider lost weight to be a risk factor for GSD in patients with hypercholesterolemia, resulting from the participants including lean individuals, who may have diet models characterized by irrational vegetarian diets during weight loss.…”