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Trial registered on ANZCTR


Registration number
ACTRN12615000579594
Ethics application status
Approved
Date submitted
10/04/2015
Date registered
3/06/2015
Date last updated
7/07/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
Development of a broader understanding of Vitamin D levels in patients undergoing sleeve gastrectomy to inform guidelines for post-surgery supplementation
Scientific title
Effects of vitamin D supplementation on the vitamin D status of morbidly obese patients post gastric sleeve surgery.
Secondary ID [1] 286508 0
none
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Vitamin D deficiency 294723 0
Morbid Obesity 294724 0
Condition category
Condition code
Diet and Nutrition 295013 295013 0 0
Obesity
Diet and Nutrition 295014 295014 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Observational
Patient registry
True
Target follow-up duration
12
Target follow-up type
Months
Description of intervention(s) / exposure
Usual care of these patients involves post-surgery supplementation with 800IU oral Vitamin D3 as part of a daily multivitamin for 12 months (Centrum) if patients’ 25(OH)D levels are greater than 50 nmol/L (sufficient) or an additional 1000IU oral Vitamin D3 (as Ostelin daily for 12 months) if 25(OH)D levels are equal to or less than 50 nmol/L.
Vitamin D status (serum 25(OH)D) will be observed over a 12 month period.
Intervention code [1] 291601 0
Not applicable
Comparator / control treatment
None
Control group
Uncontrolled

Outcomes
Primary outcome [1] 294766 0
Serum 25(OH)D
Timepoint [1] 294766 0
baseline, 6 and 12 months post surgery
Secondary outcome [1] 314012 0
Serum PTH
Timepoint [1] 314012 0
baseline, 6 and 12 months post surgery
Secondary outcome [2] 314013 0
Serum ionised Calcium
Timepoint [2] 314013 0
baseline, 6 and 12 months post surgery
Secondary outcome [3] 314014 0
BMI
Timepoint [3] 314014 0
baseline, 6 and 12 months post surgery
Secondary outcome [4] 314242 0
Dietary assessment using the Woollongong Diet history
Timepoint [4] 314242 0
baseline, 6 and 12 months post surgery
Secondary outcome [5] 314243 0
Sun exposure assessment via questionnaire designed specifically for this study based on a previously used questionnaire in the Suncorp Sun study.
Timepoint [5] 314243 0
baseline, 6 and 12 months post surgery
Secondary outcome [6] 314244 0
Expression of CYP24A1 via qPCR
Timepoint [6] 314244 0
Baseline
Secondary outcome [7] 314245 0
Expression of CYP27A1 via qPCR
Timepoint [7] 314245 0
Baseline
Secondary outcome [8] 314246 0
Expression of CYP27B1 via qPCR
Timepoint [8] 314246 0
Baseline
Secondary outcome [9] 314247 0
Expression of VDR via qPCR
Timepoint [9] 314247 0
Baseline
Secondary outcome [10] 314248 0
SNP analysis of VDR gene
Timepoint [10] 314248 0
baseline
Secondary outcome [11] 314249 0
SNP analysis of vitamin D binding protein
Timepoint [11] 314249 0
baseline

Eligibility
Key inclusion criteria
(i) Age 18-65 years
(ii) Available to participate in data collection prior to surgery, six and 12 months post surgery
(iii) Meet criteria within the International Sleeve Gastrectomy Expert Panel Consensus Statement for surgery
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
(i) Pregnant
(ii) <18yrs
(iii) Inability to provide informed consent due to diminished understanding or comprehension, or a language other than English spoken and an interpreter unavailable
(iv) Taking medications that interfere with vitamin D metabolism

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
A statistician will be consulted prior to data analysis.

Sample size
The minimum sample size needed to detect the anticipated difference of around 20nmol/L 25(OH)D levels after supplementation with 80% power and 5% type two error (2-tailed) is 45 patients. We have added 10% to this for attrition, giving a total of 50 patients.

Anthropometrics, serum 25OHD and DBP
Normal distribution of data will be assessed by visual examination of Q-Q plots. Non-normally distributed data will be transformed to achieve normality where appropriate. If transformation does not produce normal data, nonparametric tests will be used. Normally distributed data will be expressed as means and standard deviation, and non-normally distributed data will be expressed as median and standard error. Continuous data from each group will be compared using student t-test, and categorical data will be compared using chi-squared test. Significance will be set at p<0.05. The statistical software SPSS (IBM) will be used to analyse data.

Real time qualitative PCR
Relative expression of the genes of interest will be compared between time points. Results will be displayed as fold change over time. Real time qPCR efficiency will be assessed using qBASE, using a quantification model with kinetic PCR efficiency correction. Normalisation of gene expression will be achieved by adjusting Ct levels to an endogenous housekeeping gene specific for the tissue type.

Single nucleotide polymorphisms
The SNPs chosen for identification in the genes of interest have been linked to low serum 25OHD levels and/or obesity. SNP analysis will be performed at the Australian Genome Research Facility at the St Lucia Campus of the University of Queensland. Results will be displayed as count and percentage of each variant in each group.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 3689 0
The Wesley Hospital - Auchenflower
Recruitment postcode(s) [1] 9513 0
4066 - Auchenflower

Funding & Sponsors
Funding source category [1] 291076 0
Hospital
Name [1] 291076 0
The Wesley Hospital Patient Outcome Research Committee
Address [1] 291076 0
451 Coronation Drive,
Auchenflower QLD 4066
Country [1] 291076 0
Australia
Funding source category [2] 291077 0
University
Name [2] 291077 0
PhD funds from the University of Queensland
Address [2] 291077 0
University of Queensland
St Lucia
QLD 4072
Country [2] 291077 0
Australia
Primary sponsor type
University
Name
The University of Queensland
Address
University of Queensland
St Lucia
QLD 4072
Country
Australia
Secondary sponsor category [1] 289754 0
None
Name [1] 289754 0
Address [1] 289754 0
Country [1] 289754 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292659 0
University of Queensland Human Research Ethics Committee
Ethics committee address [1] 292659 0
University of Queensland
St Lucia
QLD 4072
Ethics committee country [1] 292659 0
Australia
Date submitted for ethics approval [1] 292659 0
06/01/2015
Approval date [1] 292659 0
24/03/2015
Ethics approval number [1] 292659 0
2015000446
Ethics committee name [2] 292660 0
UnitingCare Health Human Research Ethics Committee
Ethics committee address [2] 292660 0
Human Research Ethics Committee
Ground Floor Moorlands House, The Wesley Hospital
451 Coronation Drive, Auchenflower QLD 4066
PO Box 499 Toowong QLD 4066
Ethics committee country [2] 292660 0
Australia
Date submitted for ethics approval [2] 292660 0
Approval date [2] 292660 0
07/04/2015
Ethics approval number [2] 292660 0
1502

Summary
Brief summary
Surgery provides the most efficient method of weight loss in severely obese patients, but also leads to malabsorption of micronutrients. Sleeve gastrectomy is a purely restrictive procedure and removes the greater curvature of the stomach leaving a small gastric sleeve. Advantages include rapid weight loss, comorbidity reduction, and avoidance of the complications seen in bypass procedures. Nutrient deficiency in this patient group is common, with Vitamin D deficiency reported in 21-80% of patients one year post-surgery. This may predispose these patients to poorer health outcomes, as inadequate Vitamin D levels have been associated with disruptions to calcium homeostasis, impaired bone metabolism and osteoporosis, cancer, insulin resistance, diabetes, cognitive dysfunction, depression and cardiovascular disease. However, there is also current debate around whether Vitamin D levels are a marker for, rather than a cause of chronic illness. It would be expected that stored Vitamin D in the extensive adipose tissue of these patients would help correct deficient levels as weight is lost, although there is no evidence to support this in the literature.

It is possible that these patients have: (i) excess storage and potential dysfunctional metabolism and release of Vitamin D from adipose tissue; (ii) lower sun exposure and dietary intake due to lifestyle factors, or (iii) impaired synthesis and release from the skin. These mechanisms are unclear, and there are few published studies about treating Vitamin D deficiency post-surgery in this patient group and no consensus on recommendations for supplementation dosage and duration for gastric sleeve, or indeed any of the bariatric surgeries. This emphasises a significant gap in patient care recommendations.

There is currently insufficient evidence to support the development of uniform supplementation guidelines post-surgery for patients undergoing bariatric surgery, and data for sleeve gastrectomy patients is most lacking, therefore protocols for supplementation are only consensus-driven. Further understanding the effect of supplementation in gastric sleeve patients is critical, as two recent studies have suggested Vitamin D supplementation may cause net harm in other groups and a recent systematic review confirmed little to no association between 25(OH)D levels and the course of a range of diseases/conditions shown to be associated with low 25(OH)D levels in epidemiological studies (e.g. cancer, insulin resistance, diabetes, cognitive dysfunction, cardiovascular disease). Current reasoning behind this null effect includes variations in baseline levels, body mass index and genetic variations in response to supplementation.

There is significant individual variation in 25(OH)D levels pre-bariatric surgery, with most patients being deficient (<25nmol/L) or insufficient (<50nmol/L). There is also evidence for varied responses to set doses of Vitamin D3 post surgery however there is no data on this for patients undergoing sleeve gastrectomy. Genetic variation in the Vitamin D binding protein and the Vitamin D receptor in target tissues has been implicated in such variation in obese individuals. The current test for Vitamin D – serum 25(OH)D levels – does not account for this potential genetic variation, or for individual variation in Vitamin D metabolism (i.e. production of active metabolites) in tissues. Measuring the variation in genes for the Vitamin D binding protein and Vitamin D receptor alongside the response to Vitamin D supplementation would add clarity to the variations in responses to Vitamin D supplementation in order to determine evidence-based supplementation guidelines. The mechanistic work completed as part of this study will form the basis of future clinical trials to optimise supplementation strategies for these patients.

In addition to the lack of understanding of the basis of 25(OH)D levels and supplementation response in sleeve gastrectomy patients, there is no evidence of the contribution of UV exposure and diet on Vitamin D status in these patients. As UV exposure plays an important part in endogenous production of Vitamin D, this is vital. In a group with already restricted intake and a higher risk of nutrient deficiencies, understanding the influences on Vitamin D intake and production are critical to optimising sun exposure, dietary intake and supplementation practices.

Aims
*To optimise patient outcomes post gastric sleeve surgery by achieving adequate and sustained 25(OH)D levels through individualised supplementation (usual care)
*To establish the variation in 25(OH)D levels in patients undergoing gastric sleeve surgery before and 6, and 12-months after surgery to monitor the effect of usual care supplementation practices
*To examine differences in 25(OH)D levels in patients before and 6 and 12-months after gastric sleeve surgery according to direct and indirect measures of sun exposure, detailed dietary intake data, genetic variation in the circulating Vitamin D binding protein and Vitamin D receptor, to provide pilot data on the variation of individualisation required in future supplementation practice
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 52238 0
Mrs Clare Dix
Address 52238 0
Room 212, Building 26b
Centre of Dietetic Research
School of Human movement and nutrition sciences
The University of Queensland
St Lucia, QLD 4072
Country 52238 0
Australia
Phone 52238 0
+61 417 482 145
Fax 52238 0
Email 52238 0
clare.dix@uqconnect.edu.au
Contact person for public queries
Name 52239 0
Mrs Clare Dix
Address 52239 0
Room 212, Building 26b
Centre of Dietetic Research
School of Human movement and nutrition sciences
The University of Queensland
St Lucia, QLD 4072
Country 52239 0
Australia
Phone 52239 0
+61 417 482 145
Fax 52239 0
Email 52239 0
clare.dix@uqconnect.edu.au
Contact person for scientific queries
Name 52240 0
Mrs Clare Dix
Address 52240 0
Room 212, Building 26b
Centre of Dietetic Research
School of Human movement and nutrition sciences
The University of Queensland
St Lucia, QLD 4072
Country 52240 0
Australia
Phone 52240 0
+61 417 482 145
Fax 52240 0
Email 52240 0
clare.dix@uqconnect.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary