Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619001542189
Ethics application status
Approved
Date submitted
15/10/2019
Date registered
8/11/2019
Date last updated
8/11/2019
Date data sharing statement initially provided
8/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Close to the Bone: An investigation of bone health in young women with Coeliac Disease and non-coeliac gluten sensitivity compared to healthy controls.
Scientific title
An investigation of bone health in young women with Coeliac Disease and non-coeliac gluten sensitivity compared to healthy controls.
Secondary ID [1] 299522 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Coeliac disease 314808 0
Non-coeliac gluten sensitivity 314832 0
Low bone mineral density 314833 0
Osteoporosis 314834 0
Condition category
Condition code
Diet and Nutrition 313147 313147 0 0
Other diet and nutrition disorders
Inflammatory and Immune System 313168 313168 0 0
Autoimmune diseases
Oral and Gastrointestinal 313169 313169 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Musculoskeletal 313170 313170 0 0
Osteoporosis

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
This study aims to investigate bone health in women with coeliac disease (CD) and non-coeliac gluten sensitivity (NCGS) compared with matched healthy controls. This study will require participants to complete a three-day diet diary in the week prior to their visit to the research unit, to assess nutrient intake. During their visit to the research unit they will have bone health assessed (bone mineral density, DXA; Quantitative Ultrasound, QUS); complete questionnaires to assess nutrient intake and physical activity level including retrospective information about past nutrient intake and exercise. In addition they will also have venous bloods to measure bone health (bone metabolism, CTX), nutrient status (vitamin B12; folate), markers of inflammatory status (CRP), thyroid function (namely TSH-h; T3 free; T4; Tg; anti-Tg; anti-TPO), calcium homeostasis (calcium; vitamin D; parathyroid hormone) and disease status (markers of coeliac disease - tissue-transglutaminase; endomysial antibodies). The overall duration will be one visit to the research unit of about 2 hours plus additional time outside of this visit to complete a three-day diet diary. No follow up is planned.
Intervention code [1] 315800 0
Diagnosis / Prognosis
Comparator / control treatment
The control group will be young women aged 18-40 who are consuming a normal gluten containing diet and have no history of medical conditions which affect bone health.
Control group
Active

Outcomes
Primary outcome [1] 321674 0
Bone mineral density assessed through Dual X-ray Absorptiometry (DXA) and bone quality measured through Quantitative ultrasound (QUS), this is a composite outcome.
Timepoint [1] 321674 0
Date of research unit visit
Secondary outcome [1] 375849 0
Bone resorption assessed by plasma CTX-1 assay
Timepoint [1] 375849 0
Date of research unit visit
Secondary outcome [2] 375900 0
Dietary intake (composite) determined by 3-day diet diary and food frequency questionnaire assessed using the validated tools in the School of Food and Advanced Technology, Massey University
Timepoint [2] 375900 0
The 3-day diet diary will be completed within the week prior to visit to the research unit (at least 3 days prior). The food frequency questionnaire data will be collected at the visit to the Research Unit and includes questions about an average week and the previous month..
Secondary outcome [3] 375902 0
Markers of inflammatory status (C-reactive protein; CRP) assessed via venous blood sample, this an exploratory outcome.
Timepoint [3] 375902 0
Date of research unit visit
Secondary outcome [4] 375905 0
Physical activity level assessed using a modified version of the validated World Health Organization 'Global Physical Activity Questionnaire' (GPAQ)
Timepoint [4] 375905 0
Date of research unit visit
Secondary outcome [5] 375906 0
Markers for thyroid function (TSH-h, T3 free, T4, Tg, anti-Tg and anti-TPO) assessed via venous blood sample, this a composite outcome.
Timepoint [5] 375906 0
Date of research unit visit
Secondary outcome [6] 375907 0
Calcium homeostasis (plasma calcium and parathyroid hormone, PTH) assessed via venous blood sample, this is a composite outcome.
Timepoint [6] 375907 0
Date of research unit visit
Secondary outcome [7] 375908 0
Disease state measured using markers for coeliac disease assessed via venous blood (endomysial antibodies, EMA and tissue transglutaminase, tTG), this a composite outcome.
Timepoint [7] 375908 0
Date of research unit visit
Secondary outcome [8] 375909 0
Vitamin B12 status measured through venous blood sample, this is an exploratory outcome.
Timepoint [8] 375909 0
Date of research unit visit
Secondary outcome [9] 376545 0
Vitamin D status assessed via venous blood sample, this is an exploratory outcome.
Timepoint [9] 376545 0
Date of research unit visit
Secondary outcome [10] 376546 0
Folate measured through venous blood sample, this is an exploratory outcome.
Timepoint [10] 376546 0
Date of research unit visit
Secondary outcome [11] 376547 0
Iron status measured through finger prick blood sample, this is an exploratory outcome.
Timepoint [11] 376547 0
Date of research unit visit

Eligibility
Key inclusion criteria
To become a participant, you will need to:
- Be a healthy female consuming a normal gluten-containing diet.
OR
- Be a female medically diagnosed with coeliac disease (by biopsy), who has consumed a strict gluten free diet for at least 12 months
OR
- Be a female medically diagnosed with non-coeliac gluten sensitivity (i.e. have received a negative diagnosis for coeliac disease by serology and biopsy but have been medically advised to adhere to a GF diet due to improvements in symptoms), who has consumed a strict gluten free diet for at least 12 months
AND
- Be aged between 18-40 years
- Live in the Palmerston North and Wellington Regions
Minimum age
18 Years
Maximum age
40 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Previous/current medication affecting bone metabolism (e.g. corticosteroids, bisphosphonates, selective oestrogen receptor modulators); medical conditions affecting bone health; pregnancy and lactation; known history of inflammatory conditions other than CD and NCGS; BMI>30 (derived from screening questionnaire); have not had your condition medically diagnosed according to standard criteria (for the CD and NCGS group).

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Defined population
Timing
Both
Statistical methods / analysis
Sample size is based on power calculations to see a difference in bone mineral density between people with Coeliac Disease (CD) and healthy controls. To detect a difference between these two groups, 39 participants are required in each group with effect size 0.41 at power 0.95 and probability of type 1 error 0.05 [1]. It is difficult to determine the number of participants required for the non-coeliac gluten sensitivity (NCGS) group to gain a significant result due to limited prior research in this area. Previous research investigating risk of osteoporosis in this group has investigated both genders and did not compare findings with age- and sex-matched healthy controls. Based on the previous research, we hypothesise that bone mineral density will be higher in the NCGS group than CD [2], but lower than healthy controls. Sample size is calculated as 141 (47 in each group), factoring in incomplete data sets/misdiagnosis of 20%. This will allow us to determine the difference in bone mineral density between these.

1. Szymczak, J. et al. Low bone mineral density in adult patients with coeliac disease. Endocrynol. Pol. 63, 270-276 (2012).
2. Carroccio, A. et al. Risk of low bone mineral density and low body mass index in patients with non-celiac wheat-sensitivity: a prospective observation study. BMC. Med. 12, 230 (2014).

Statistical analyses will be carried out using R statistical software. The Schofield equation will be used to calculate the metabolic rate. The ratio of energy intake (EI) to basal metabolic rate (BMR) will be used to evaluate relative accuracy of reported energy intake using the Goldberg cut-off. The ratio EI:BMR as defined by WHO/FAO/UNU:- 1.27 for minimum survival level, 1.56 for sedentary level and 2.0-2.4 for maximum sustainable lifestyle level will be used to compare the degree of underreporting and over-reporting in the subjects.
Descriptive, repeated measures ANOVA, correlation, linear regression will be used. A P value of < 0.05 will be considered as significant.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
18/11/2019
Actual
Date of last participant enrolment
Anticipated
31/12/2020
Actual
Date of last data collection
Anticipated
31/01/2021
Actual
Sample size
Target
141
Accrual to date
Final
Recruitment outside Australia
Country [1] 21922 0
New Zealand
State/province [1] 21922 0
Lower North Island

Funding & Sponsors
Funding source category [1] 304015 0
University
Name [1] 304015 0
School of Food & Advanced Technology Postgraduate Funding, Massey University
Country [1] 304015 0
New Zealand
Primary sponsor type
University
Name
Massey University
Address
School of Food & Advanced Technology
Massey University
Private Bag 11222
Palmerston North 4442
Country
New Zealand
Secondary sponsor category [1] 304189 0
None
Name [1] 304189 0
Address [1] 304189 0
Country [1] 304189 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304507 0
Massey University Human Ethics Committee: Southern A
Ethics committee address [1] 304507 0
Chairperson
Research Centre for Maori Health & Development
Massey University
Private Bag 11222
Palmerston North 4442
New Zealand
Ethics committee country [1] 304507 0
New Zealand
Date submitted for ethics approval [1] 304507 0
24/10/2018
Approval date [1] 304507 0
08/02/2019
Ethics approval number [1] 304507 0
SOA 18/73

Summary
Brief summary
Osteoporosis is a frequent finding in people with Coeliac Disease at the time of diagnosis; rigorous compliance with a gluten-free diet after diagnosis does not result in full recovery of bone health in a significant proportion of individuals.

We hypothesise that the Gut-Bone Axis becomes dysfunctional in Coeliac Disease and that the bone tissue continues to produce signals which affect bone turnover and cause the gut to be persistently inflamed, compromising nutrient absorption and promoting hypersensitivity to dietary components.

We will compare bone health (by a DXA scan of bone mineral density and Quantitative Ultrasound (QUS)) and bone metabolism (using blood-borne markers of bone turnover) and nutrient status in women with Coeliac Disease, with healthy controls and women who have Non-Coeliac Gluten Sensitivity.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 97190 0
Mrs Katie Schraders
Address 97190 0
School of Food and Advanced Technology
Massey University
Private Bag 11222
Palmerston North 4442
Country 97190 0
New Zealand
Phone 97190 0
+64 277237435
Fax 97190 0
Email 97190 0
[email protected]
Contact person for public queries
Name 97191 0
Mrs Katie Schraders
Address 97191 0
School of Food and Advanced Technology
Massey University
Private Bag 11222
Palmerston North 4442
Country 97191 0
New Zealand
Phone 97191 0
+64 277237435
Fax 97191 0
Email 97191 0
[email protected]
Contact person for scientific queries
Name 97192 0
Prof Marlena Kruger
Address 97192 0
School of Health Sciences
Massey University
Private Bag 11222
Palmerston North 4442
Country 97192 0
New Zealand
Phone 97192 0
+64 6 9517571
Fax 97192 0
Email 97192 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No ethics approval for this aspect.


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.