ANZCTR - Registration

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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]

none

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Vitamin D deficiency

Morbid Obesity

Condition category

Condition code

Diet and Nutrition

Obesity

Diet and Nutrition

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]

Not applicable

Comparator / control treatment

None

Control group

Uncontrolled

Outcomes

Primary outcome [1]

Serum 25(OH)D

Timepoint [1]

baseline, 6 and 12 months post surgery

Secondary outcome [1]

Serum PTH

Timepoint [1]

baseline, 6 and 12 months post surgery

Secondary outcome [2]

Serum ionised Calcium

Timepoint [2]

baseline, 6 and 12 months post surgery

Secondary outcome [3]

BMI

Timepoint [3]

baseline, 6 and 12 months post surgery

Secondary outcome [4]

Dietary assessment using the Woollongong Diet history

Timepoint [4]

baseline, 6 and 12 months post surgery

Secondary outcome [5]

Sun exposure assessment via questionnaire designed specifically for this study based on a previously used questionnaire in the Suncorp Sun study.

Timepoint [5]

baseline, 6 and 12 months post surgery

Secondary outcome [6]

Expression of CYP24A1 via qPCR

Timepoint [6]

Baseline

Secondary outcome [7]

Expression of CYP27A1 via qPCR

Timepoint [7]

Baseline

Secondary outcome [8]

Expression of CYP27B1 via qPCR

Timepoint [8]

Baseline

Secondary outcome [9]

Expression of VDR via qPCR

Timepoint [9]

Baseline

Secondary outcome [10]

SNP analysis of VDR gene

Timepoint [10]

baseline

Secondary outcome [11]

SNP analysis of vitamin D binding protein

Timepoint [11]

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

Sex

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

26/05/2015

Actual

5/05/2015

Date of last participant enrolment

Anticipated

27/10/2015

Actual

27/10/2015

Date of last data collection

Anticipated

Actual

20/12/2016

Sample size

Target

50

Accrual to date

Final

49

Recruitment in Australia

Recruitment state(s)

QLD

Recruitment hospital [1]

The Wesley Hospital - Auchenflower

Recruitment postcode(s) [1]

4066 - Auchenflower

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

The Wesley Hospital Patient Outcome Research Committee

Address [1]

451 Coronation Drive,
Auchenflower QLD 4066

Country [1]

Australia

Funding source category [2]

University

Name [2]

PhD funds from the University of Queensland

Address [2]

University of Queensland
St Lucia
QLD 4072

Country [2]

Australia

Primary sponsor type

University

Name

The University of Queensland

Address

University of Queensland
St Lucia
QLD 4072

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

University of Queensland Human Research Ethics Committee

Ethics committee address [1]

University of Queensland
St Lucia
QLD 4072

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

06/01/2015

Approval date [1]

24/03/2015

Ethics approval number [1]

2015000446

Ethics committee name [2]

UnitingCare Health Human Research Ethics Committee

Ethics committee address [2]

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]

Australia

Date submitted for ethics approval [2]

Approval date [2]

07/04/2015

Ethics approval number [2]

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

Mrs Clare Dix

Address

Room 212, Building 26b
Centre of Dietetic Research
School of Human movement and nutrition sciences
The University of Queensland
St Lucia, QLD 4072

Country

Australia

Phone

+61 417 482 145

Fax

Email

[email protected]

Contact person for public queries

Name

Clare Dix

Address

Room 212, Building 26b
Centre of Dietetic Research
School of Human movement and nutrition sciences
The University of Queensland
St Lucia, QLD 4072

Country

Australia

Phone

+61 417 482 145

Fax

Email

[email protected]

Contact person for scientific queries

Name

Clare Dix

Address

Room 212, Building 26b
Centre of Dietetic Research
School of Human movement and nutrition sciences
The University of Queensland
St Lucia, QLD 4072

Country

Australia

Phone

+61 417 482 145

Fax

Email

[email protected]

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.