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LOAD trial

LOAD trial to assess vitamin D in omega loop GB patients

A vitamin D loading dose and repeat doses in patients undergoing bariatric surgery

Researchers in Austria have completed enrolment in a trial that is examining the effects and safety of a forced dosing regimen of vitamin D versus conventional dose supplementation on vitamin D levels and other parameters in patients undergoing undergo omega-loop gastric bypass (OLGB). There are limited data on therapeutic strategies for vitamin D deficiency in bariatric patients, and the procedure-specific guidelines may not be sufficient. The investigators said that to improve long-term outcomes, nutritional screening and appropriate supplementation to prevent nutrient deficiencies are urgently needed. A description of the trial has been published in the journal Trials.

This prospective, double-blind, randomised controlled intervention trial includes administration of a vitamin D loading dose and repeat doses in patients undergoing bariatric surgery. In this study, 50 bariatric patients planning to undergo OLGB will be recruited. Over the first month postoperatively (day 1–3, weeks 2 and 4), they will receive the loading dose of vitamin D. Afterwards, the maintenance dose will be given up to 24 weeks and until the follow-up visit. An overview of the study design and the assessment points is provided in Figure 1.

Study design and assessment points

The study includes loading plus repeat dosing compared with repeated administration of vitamin D without a loading dose, according to guidelines, in a prospective, double-blind, randomized controlled trial. Up to a triple oral loading dose is given on day 1, then 2 and 4 weeks after surgery (100,000 IU dose each time), followed by an oral maintenance dose (3420 IU/day). The control group (n = 25) will receive placebo, followed by administration of a standard dose (3420 IU/day). We hypothesize that a significant increase in vitamin D levels will occur in patients in the treatment group (n = 25) by 24 weeks after surgery. Further measurements are aimed at evaluating changes in inflammation, bone turnover, insulin resistance, blood pressure, liver, mental health, and gut microbiota of patients undergoing omega-loop gastric bypass surgery. Furthermore, possible associations between concentrations of vitamin D, the involved enzymes, or vitamin D receptor in adipose and/or liver tissues will be determined.

“To our knowledge, this trial is the first of its kind with this type of vitamin D supplementation in bariatric patients,” the authors write. “Its major strength is the design and implementation of evaluation of influencing factors such as liver function, bone health, inflammation, insulin resistance, blood pressure, symptoms of depression, or microbiota. This alternative vitamin D dosing regimen has the potential to be a safe, fast, evidence-based treatment of vitamin D deficiency in bariatric patients. Owing to the increasing number of bariatric patients, it is also of interest to elucidate the link between obesity and vitamin D.”

The methods in this study are built upon a cohort study in which investigators evaluated inter alia the vitamin D status of 50 morbidly obese patients who underwent OLGB [54]. The findings of the evaluation illustrated that 96 % had vitamin D deficiency preoperatively and that, after non-standardised vitamin D supplementation, 80 % still had vitamin D deficiency 12 months postoperatively [54]. Additionally, there is evidence that, despite forced vitamin D supplementation, some patients are still at risk for increased bone resorption. It could be possible that morbidly obese patients might need higher 25-OHD levels to reduce the risk for developing metabolic bone disease, osteoporosis or other associated disorders.

The primary objective of the present study is to examine whether administration of up to three oral loading doses in the first month postoperatively (day 1 and at weeks 2 and 4), followed by an oral maintenance dose (intervention group) in bariatric patients can significantly increase 25-OHD levels 24 weeks after surgery as compared with a control group receiving placebo followed by the standard daily maintenance dose (control group).

The researchers have recruited bariatric patients planning to undergo OLGB and who are in- and/or outpatients in the obesity clinic at the Department of Internal Medicine III or the Department of Surgery at Vienna General Hospital.

The study is powered to detect differences among the groups for 24-week serum 25-OHD levels. On basis of the preevaluation (cohort study), the placebo group was conservatively estimated to have an average 24-week 25-OHD level of 50 ± 30 nmol/L. For sample size calculation, the difference in 25-OHD levels between groups will be considered. Given a clinically relevant difference of 30 nmol/L and a standard deviation of 35 nmol/L of the differences, a two-sided significance level of 0.05, a sample size of 22 per group is needed to reach 80 % statistical power. Because imputation for dropouts of 20 % may have some inestimable effect on the assumed standard deviation of the differences, the sample size is increased to 25 per group. To reach this sample size, a total of 50 bariatric patients in the study are needed. The primary endpoint will be analysed according to the intention-to-treat principle.

Subjects were randomly assigned to the intervention or control group. According to the current guidelines, a minimal daily vitamin D supplementation of at least 3000 IU is recommended. In order to prevent failure of the study due to an insufficient treatment dose, the researchers chose the maximum loading dose for which sufficient safety data are available.

Figure 2: Dosing regimen. [25 - OHD 25-hydroxy vitamin D]

The functional half-life for vitamin D 3 in the body is between 2 and 3 months. As a result, the loading dose can be calculated as the cumulative maintenance dose that is planned to be given through one functional half-life of vitamin D, as follows:

Patient history and dietary assessment data are documented at baseline and collected four times. For all subjects, body weight, body composition, and blood parameters are assessed eight times. The liver function assessment is done four times. Blood pressure, depression symptoms, BMD, and total body fat mass are measured two times in all study groups. The visit and assessment schedule are shown in Figure 3.

Figure 3: Flowchart [BMD bone mineral density]

“Vitamin D supplementation regimen has the potential to be a safe, orally available, cheap, and evidence-based treatment of low vitamin D status following bariatric surgery in this increasingly prevalent group, and the study probably also is an opportunity to find an association between obesity and vitamin D deficiency,” they conclude.

The LOAD study commenced recruitment in April 2014 and recruitment was completed in April 2015.

To access this paper, please click here

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