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Trial registered on ANZCTR


Registration number
ACTRN12617000779370
Ethics application status
Approved
Date submitted
25/05/2017
Date registered
29/05/2017
Date last updated
29/05/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Acute effect of high calcium milk and calcium supplement on bone health in thin and overweight post-menopausal women
Scientific title
Acute effects of high calcium milk and calcium supplementation on Bone Resorption Marker (serum CTX, C-telopeptide of type 1 collagen) in thin and overweight post-menopausal women.
Secondary ID [1] 291798 0
None
Universal Trial Number (UTN)
U1111-1196-0744
Trial acronym
Linked study record
None

Health condition
Health condition(s) or problem(s) studied:
Bone health in overweight postmenopausal women 303030 0
Condition category
Condition code
Musculoskeletal 302488 302488 0 0
Osteoporosis
Diet and Nutrition 302868 302868 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a randomized open-labeled crossover study. The participants will be recruited through Facebook advertisement. Interested participants will attend the clinical trial facility at the University of South Australia on four different occasions, one week apart. During the screening visit, all subjects will undergo body weight measurements, standing height and waist-hip ratio (WHR). Based on their body mass index (BMI), participants will be recruited such that we have 66 each in the thin (BMI less than or equal to 25 Kg/m2) and overweight group (BMI greater than 27 kg/m2). Each enrolled participants will be assigned a code known only to the investigator and a randomization sequence for the three products will be generated. The following week, participants will return to the laboratory. On each of the test day, blood samples will be collected at baseline (after 12 hours overnight fast). Each participant will then be administered a single dose of any one product based on their respective randomization sequence and will be asked to consume the same within 15min. The time at which they finish the drink will be recorded and referred to as time zero. Blood samples will then be collected subsequently at 30 min, 1, 2, 3, 4 and 5 hour time points. The products will be:

Experimental Arm 1: Two pills of Calcium carbonate
Experimental Arm 2: High calcium milk
Control arm: A non-fortified fruit drink

The products in the experimental arms 1 and 2 will deliver 1000mg calcium each.

Each intervention will be separated by a washout period of one week, hence every participant will act as her own control. Body composition will be assessed using Dual-X-ray Absorptiometry (DEXA) at any of the visits based on participant convenience.

Intervention code [1] 297913 0
Prevention
Comparator / control treatment
The comparator will be a non-fortified fruit juice
Control group
Active

Outcomes
Primary outcome [1] 301911 0
The primary outcome of the study will be the response to serum CTX levels.
Timepoint [1] 301911 0
Baseline (overnight fast) and at 0.5,1,2,3,4,5 hours time point after consumption of the test product.
Secondary outcome [1] 334263 0
Serum PTH
Timepoint [1] 334263 0
Baseline (overnight fast) and at 0.5,1,2,3,4,5 hours time point after consumption of the test product.
Secondary outcome [2] 334451 0
Serum calcium (ionized)
Timepoint [2] 334451 0
Baseline (overnight fast) and at 0.5,1,2,3,4,5 hours time point after consumption of the test product.
Secondary outcome [3] 334452 0
Serum GLP-2 (Glucagon like Peptide- 2)
Timepoint [3] 334452 0
Baseline (overnight fast) and at 0.5,1,2,3,4,5 hours time point after consumption of the test product.
Secondary outcome [4] 334453 0
Serum GLP-1
Timepoint [4] 334453 0
Baseline (overnight fast) and at 0.5,1,2,3,4,5 hours time point after consumption of the test product.
Secondary outcome [5] 334454 0
Serum GIP
Timepoint [5] 334454 0
Baseline (overnight fast) and at 0.5,1,2,3,4,5 hours time point after consumption of the test product.
Secondary outcome [6] 334457 0
Serum phosphate
Timepoint [6] 334457 0
Baseline (overnight fast) and at 0.5,1,2,3,4,5 hours time point after consumption of the test product.
Secondary outcome [7] 334458 0
Serum P1NP
Timepoint [7] 334458 0
Baseline (overnight fast) and at 0.5,1,2,3,4,5 hours time point after consumption of the test product.

Eligibility
Key inclusion criteria
Apparently healthy post-menopausal women, at least 5 years since menopause with BMI less than 25kg/m2 or greater than 27kg/m2
Minimum age
50 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Post-menopausal women (at least 5 years post-menopause) who are :
1. On any prescribed osteoporotic medication (e.g. Prolia, Alendronate, Zoledronate etc.)
2. Lactose intolerant
3. Diabetic
4. Have kidney disorders



Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
An independent holder of the randomisation schedule who will have no contact with the volunteers will perform treatment allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Volunteers who meet eligibility criteria will be randomly allocated to one of three treatments using a computerized random code generator


Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Data Analyses : For data analyses, subjects will be divided in to two groups based on median trunk fat values measured by DXA and Student’s t tests will be used to compare the groups. The effects of each treatment will be assessed by two methods. The mean maximal suppression of CTX and a mean maximal rise in GLP-2 will be calculated and expressed as percent change from the baseline value for each subject and the effect of high calcium milk and calcium supplement compared with fruit drink will be assessed by two-tailed Student’s t-test at each time-point. As well the areas under the curves (AUC) from baseline to 5 hours will be calculated using the trapezoidal method, and ANOVA will be carried out using the General Linear Method Procedure. Correlation analysis will be carried out to describe relationships between trunk fat mass, maximum suppression of CTX and maximum rise in GLP-2. A multivariate test for repeated measures of the variance of CTX and GLP-2 will be carried out by means of the General Linear Model to assess the time course dependency, intervention effect, and the interaction between time and intervention effect. Statistical software packages (GraphPad and SPSS) will be used for the analyses. Data will be presented as mean +/-SEs and P< 0.05 will be considered significant
Power calculations: We assume that a 30% difference in change in CTX level between the groups (primary outcome variable) would be biologically significant. There are no data on the effect of calcium supplement or dietary calcium in suppressing CTX levels in overweight/obese women. Based on previously published data on the effect of calcium in reducing CTX levels in healthy men and post-menopausal women, we estimate that 66 women per group will be required to show statistically significant difference at 80% power (a=0.05) and two-sided t-test and a 10% drop out rate,

Recruitment
Recruitment status
Not yet recruiting
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)
SA
Recruitment postcode(s) [1] 15896 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 296301 0
University
Name [1] 296301 0
University of South Australia
Address [1] 296301 0
GPO Box 2471, Adelaide 5001, South Australia
Country [1] 296301 0
Australia
Primary sponsor type
University
Name
University of South Australia
Address
University of South Australia
GPO Box 2471, Adelaide 5001, South Australia
Country
Australia
Secondary sponsor category [1] 295228 0
Individual
Name [1] 295228 0
Prof Howard Morris
Address [1] 295228 0
SA Pathology, IMVS Building,Chemical Pathology Directorate, Level 2
Frome Rd, Adelaide SA 5000
Country [1] 295228 0
Australia
Secondary sponsor category [2] 295291 0
Individual
Name [2] 295291 0
A/Prof Paul Anderson
Address [2] 295291 0
Musculoskeletal Biology Research Laboratory, School of Pharmacy and Medical Sciences,University of South Australia
2-58-N IMVS Building,
SA Pathology,
Frome Rd, Adelaide, SA, 5000
Country [2] 295291 0
Australia
Secondary sponsor category [3] 295292 0
Individual
Name [3] 295292 0
Prof Peter Clifton
Address [3] 295292 0
School of Pharmacy and Medical Sciences, Level 5 room P5-16 Playford Building University of South Australia, GPO Box 2471
Adelaide SA 5001 Australia
Country [3] 295292 0
Australia
Secondary sponsor category [4] 295293 0
Individual
Name [4] 295293 0
Deepti katyal Sharma
Address [4] 295293 0
Musculoskeletal Biology Research Laboratory, School of Pharmacy and Medical Sciences, University of South Australia
2-58-N IMVS Building,
SA Pathology,
Frome Rd, Adelaide, SA, 5000

Country [4] 295293 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297531 0
Universtiy of south Australia Human research Ethics Committee
Ethics committee address [1] 297531 0
University of South Australia
Mawson Lakes Campus, Mawson Boulevard, Mawson Lakes, SA 5095
Ethics committee country [1] 297531 0
Australia
Date submitted for ethics approval [1] 297531 0
28/02/2017
Approval date [1] 297531 0
15/05/2017
Ethics approval number [1] 297531 0
36365

Summary
Brief summary
Our research focuses on nutritional strategies for bone health to prevent osteoporosis and reduce the risk of fractures in overweight post-menopausal women. Osteoporosis and obesity both impose major cost burdens for their associated care. There is increasing evidence of a high prevalence of fractures in overweight and obese people. There are approximately 400 fractures per day in Australia as a result of osteoporosis. Breaking a bone is very painful but there are longer term effects such as difficulty in walking and it has now been shown that fracture contribute to premature death. Osteoporosis arises when bones lose calcium more quickly than it can be replaced, reducing their strength. Although only a small amount of calcium is present in blood; this calcium is essential for the functioning of the heart, muscles and nerves. So far, studies have mainly investigated impact of calcium supplementation in reducing bone loss in normal weight women. However there are increasing numbers of overweight women in our community and therefore it could be that dietary calcium does not have the same benefits for bone health in overweight women as it does in thin women.
Our research aims to answer two important questions:-
1) Can dietary calcium protect the bones of overweight and obese post-menopausal women?
2) Which form of calcium intake, calcium from food or calcium as supplement, is
better for overweight/obese post-menopausal women.

Trial website
NA
Trial related presentations / publications
NA
Public notes

Contacts
Principal investigator
Name 74350 0
Mrs Deepti katyal Sharma
Address 74350 0
Musculoskeletal Biology Research Laboratory, School of Pharmacy and Medical Sciences, University of South Australia
2-58-N IMVS Building,
SA Pathology,
Frome Rd, Adelaide, SA, 5000

Country 74350 0
Australia
Phone 74350 0
+61 8 8222 3514
Fax 74350 0
Email 74350 0
deepti.sharma@mymail.unisa.edu.au
Contact person for public queries
Name 74351 0
Prof Howard Morris
Address 74351 0
SA Pathology, IMVS Building, Chemical Pathology Directorate, Level 2
Frome Rd, Adelaide SA 5000
Country 74351 0
Australia
Phone 74351 0
+61 8 8222 3031
Fax 74351 0
Email 74351 0
howard.morris@sa.gov.au
Contact person for scientific queries
Name 74352 0
Prof Howard Morris
Address 74352 0
SA Pathology, IMVS Building, Chemical Pathology Directorate, Level 2
Frome Rd, Adelaide SA 5000
Country 74352 0
Australia
Phone 74352 0
+61 8 8222 3031
Fax 74352 0
Email 74352 0
howard.morris@sa.gov.au

No data has been provided for results reporting
Summary results
Not applicable