The Link Between Obesity And Vitamin D in Bariatric Patients With Omega-loop Bypass Surgery (LOAD)

The Link Between Obesity And Vitamin D in Bariatric Patients With Omega-loop Bypass Surgery: a Randomized Controlled, Double-blinded Clinical Supplementation Trial

The aim of the study is to increase vitamin D concentrations or to keep it on high level, respectively, by supplementing with vitamin D3 in a different dose regime, and to improve the overall health status in bariatric patients. In this project, the vitamin D status, the parameters of inflammation, bone turnover, insulin resistance, liver and depression score of bariatric patients are expected to improve, due to supplementation of a loading dose compared to the standard therapy.

Study Overview

• Status: Completed
• Conditions: Bariatric Surgery Candidate
• Intervention / Treatment: Drug: Placebo; Drug: Cholecalciferol

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Medical University of Vienna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Planned omega loop bypass surgery
• 25-hydroxy vitamin D < 75 nmol/l
• BMI >40 or ≥35 kg/m2 with co-morbidities e.g. diabetes mellitus, hypertension
• Body weight <140 kg (due to limitation of DEXA measurement)
• Capability to consent

Exclusion Criteria:

• Another planned form of bariatric surgery
• Hypercalcemia (calcium >2.63 mmol/l) or hypocalcemia (<1.75 mmol/l)
• Renal insufficiency (creatinine >133 μmol/l or GFR <50 ml/min)
• Primary hyperparathyroidism
• Malignancy
• Infection e.g. human immunodeficiency virus
• Medical conditions requiring daily calcium supplements or antacid use
• Known hypersensitivity to cholecalciferol
• No capability to consent
• Imprisoned persons

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intervention; The loading dose of 300 000 IU is divided into three doses (100 000 IU) and will be given over the first months. All patients in the intervention group will receive the first loading dose of 100 000 IU at day of discharge. The second (2 weeks) and third (4 weeks postoperative) administration will be given based on the 25-hydroxy vitamin D concentration. After the last respectively third loading dose a maintenance dose of 3420 IU per day should maintain the high 25-hydroxy vitamin D concentration. It should be administered for up to 46 weeks (until follow-up visit)	Drug: Cholecalciferol
Placebo Comparator: Placebo; The placebo loading dose (oil) is divided into three administrations and will be given over the first months. All patients in the placebo group will receive the first placebo loading dose at day of discharge. After the last placebo loading dose a maintenance dose of 3420 IU per day should maintain the 25-hydroxy vitamin D concentration. It should be administered for up to 46 weeks (until follow-up).	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
25-hydroxy vitamin D levels	25-hydroxy vitamin D levels after 24 weeks measured in intervention and placebo group, adjusting for the baseline value as covariate	24 weeks postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of sufficient vitamin D	Number of patients reaching 25-hydroxyvitamin D levels above 75 nmol/l	24 weeks postoperatively
Prevalence of vitamin D deficiency	Prevalence of vitamin D deficiency	24 weeks postoperatively
Co-morbidities	Prevalence of Co-morbidities	24 weeks postoperatively
Prescribed medication	Change in prescribed medication	24 weeks postoperatively
Body weight, body composition	Change in body weight and body composition by bioelectrical impedance analysis	24 weeks postoperatively
Blood pressure	Change of vital signs (blood pressure)	24 weeks postoperatively
Laboratory parameters	Change in laboratory parameters compared to baseline: vitamin D status, bone turnover markers, calcium homeostasis, parathyroid hormone, inflammation, insulin resistance	24 weeks postoperatively
Depression symptoms	Prevalence of depression symptoms assessed by Beck Depression Inventory Questionnaire	24 weeks postoperatively
Bone mineral density and body fat content	Assessment of bone mineral density and total body fat content by DEXA	24 weeks postoperatively
Liver condition	Measurement of liver stiffness and fat content by FibroScan and CAP	24 weeks postoperatively
Dietary assessment	Dietary assessment will be documented with a 5-day food record to calculate vitamin D intake and the Mediterranean Score (questionnaire with calculated score)	24 weeks postoperatively
Gut microbiota composition	Association between vitamin D, gut microbiota and surgery-induced weight loss, by collecting stool samples	24 weeks postoperatively
Vitamin D in adipose and liver tissue	For instance, for the purposes of describing adipose depot vitamin D concentrations and expression of enzymes in subcutaneous, visceral adipose and liver tissue samples will be collected during the omega loop gastric bypass surgery. Furthermore, the liver tissue samples should be used in addition for a histological examination as extended diagnostics (NAFLD/ NASH).	during surgery

Collaborators and Investigators

• Sponsor: Maria Luger
• Investigators: Principal Investigator: Bernhard Ludvik, M.D., Division of Endocrinology & Metabolism, Department of Internal Medicine III, Medical University of Vienna

Publications and helpful links

General Publications

• Kruschitz R, Wakolbinger M, Schindler K, Prager G, Hoppichler F, Marculescu R, Ludvik B. Effect of one-anastomosis gastric bypass on cardiovascular risk factors in patients with vitamin D deficiency and morbid obesity: A secondary analysis. Nutr Metab Cardiovasc Dis. 2020 Nov 27;30(12):2379-2388. doi: 10.1016/j.numecd.2020.08.011. Epub 2020 Aug 20.
• Luger M, Kruschitz R, Winzer E, Schindler K, Grabovac I, Kainberger F, Krebs M, Hoppichler F, Langer F, Prager G, Marculescu R, Ludvik B. Changes in Bone Mineral Density Following Weight Loss Induced by One-Anastomosis Gastric Bypass in Patients with Vitamin D Supplementation. Obes Surg. 2018 Nov;28(11):3454-3465. doi: 10.1007/s11695-018-3353-2.
• Luger M, Kruschitz R, Kienbacher C, Traussnigg S, Langer FB, Prager G, Schindler K, Kallay E, Hoppichler F, Trauner M, Krebs M, Marculescu R, Ludvik B. Vitamin D3 Loading Is Superior to Conventional Supplementation After Weight Loss Surgery in Vitamin D-Deficient Morbidly Obese Patients: a Double-Blind Randomized Placebo-Controlled Trial. Obes Surg. 2017 May;27(5):1196-1207. doi: 10.1007/s11695-016-2437-0.
• Luger M, Kruschitz R, Kienbacher C, Traussnigg S, Langer FB, Schindler K, Wurger T, Wrba F, Trauner M, Prager G, Ludvik B. Prevalence of Liver Fibrosis and its Association with Non-invasive Fibrosis and Metabolic Markers in Morbidly Obese Patients with Vitamin D Deficiency. Obes Surg. 2016 Oct;26(10):2425-32. doi: 10.1007/s11695-016-2123-2.
• Luger M, Kruschitz R, Marculescu R, Haslacher H, Hoppichler F, Kallay E, Kienbacher C, Klammer C, Kral M, Langer F, Luger E, Prager G, Trauner M, Traussnigg S, Wurger T, Schindler K, Ludvik B. The link between obesity and vitamin D in bariatric patients with omega-loop gastric bypass surgery - a vitamin D supplementation trial to compare the efficacy of postoperative cholecalciferol loading (LOAD): study protocol for a randomized controlled trial. Trials. 2015 Aug 5;16:328. doi: 10.1186/s13063-015-0877-9.

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: March 17, 2014
• First Submitted That Met QC Criteria: March 19, 2014
• First Posted (Estimate): March 20, 2014

Study Record Updates

• Last Update Posted (Estimate): July 14, 2016
• Last Update Submitted That Met QC Criteria: July 13, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Bariatric surgery; supplementation; vitamin D
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: LOAD; 2013-003546-16 (EudraCT Number)