Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12611000232932
Ethics application status
Approved
Date submitted
21/02/2011
Date registered
3/03/2011
Date last updated
27/03/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
A Randomised Control Trial to Compare the Effects of Hydroxyapatite Preparations, Calcium Citrate and Calcium Carbonate on Serum Calcium and Markers of Bone Turnover in Healthy Postmenopausal Women.
Scientific title
In healthy postmenopausal women what are the effects of hydroxyapatite preparations compared with calcium citrate and calcium carbonate on serum calcium and markers of bone turnover?
Secondary ID [1] 253310 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteoporosis 258843 0
Vascular disease 258844 0
Condition category
Condition code
Metabolic and Endocrine 258983 258983 0 0
Other metabolic disorders
Musculoskeletal 259410 259410 0 0
Osteoporosis
Cardiovascular 259411 259411 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
There will be five intervention arms as follows:
Arm 1: 1g of calcium as citrate
Arm 2: 1g of calcium as carbonate
Arm 3: 1g of calcium as hydroxyapatite preparation A*
Arm 4: 1g of calcium as hydroxyapatite preparation B*
Arm 5: placebo containing no calcium (microcrystalline cellulose)
* Process manipulations will result in two preparation variants that will differ in their particle density and size distribution, food chemistry (moisture, fat, protein, ash) ratios and the extent of enzyme hydrolysis


The mode of administration is by oral capsule, with 8 capsules providing 1g of calcium. On day 1, each preparation will be taken in a single dose of eight capslues . For the remainder of the trial period, the trial medications will be taken in two divided doses daily, four capsules in the morning and four in the evening.

The duration of administration is 12 weeks.
Intervention code [1] 257763 0
Prevention
Comparator / control treatment
Microcrystalline cellulose capsules.
Control group
Placebo

Outcomes
Primary outcome [1] 259837 0
Change in serum calcium (total and ionised) following the first supplement dose at baseline.
Timepoint [1] 259837 0
0, 2, 4, 6 and 8 hours after the first supplement dose at baseline. 20% of participants will have serum calcium measurements repeated at week 12 following their final supplement dose.
Primary outcome [2] 259838 0
Change in markers of bone turnover (PINP, parathyroid hormone and beta-C-telopeptide) will be measured by plasma and serum analysis.
Timepoint [2] 259838 0
Baseline and 12 weeks from baseline
Secondary outcome [1] 268691 0
Changes in indices of blood coagulation following the first supplement dose at baseline will be measured by thromboelastography.
Timepoint [1] 268691 0
0, 2, 4, 6 and 8 hours after the first supplement dose at baseline.
Secondary outcome [2] 268692 0
Changes in indices of vascular function (fetuin A, others to be confirmed) will be measured by plasma and serum analysis.
Timepoint [2] 268692 0
Baseline and 12 weeks from baseline.

Eligibility
Key inclusion criteria
Female, postmenopausal 5 years or more (menopause defined as at least 12 months since last period in a woman aged > 45 yrs with intact uterus, or serum oestradiol < 100 pmol/l with FSH > 50 IU/l in younger or hysterectomised woman).
Minimum age
No limit
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Past history of coronary heart disease, cerebrovascular disease or peripheral vascular disease, estimated 5-year cardiovascular risk >15%, renal impairment (serum creatinine >0.15 mmol/L), chronic liver disease, untreated hypothyroidism or hyperthyroidism, concurrent major systemic illness (including malignancy), active major gastrointestinal disease, metabolic bone diseases, or serum ALP >normal, primary hyperparathyroidism, current or expected use of oral glucocorticoid drugs during the trial period, current or past use of bisphosphonate therapy in the preceding 2 years, use of hormone replacement therapy within the last 12 months, use of other medication known to cause osteoporosis or interfere with bone metabolism.

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)
Each enrolled patient will be provided with a sequential study registration number and, if they met the inclusion criterion and are not excluded, will be sequentially allocated to one of five treatment arms at random by sealed envelope.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A variable block size randomization schedule will be prepared by staff not involved in the management of the trial. For each block of patients a random number will be generated. Patient numbers in the lowest fifth by random number, will receive 1 g of calcium as hydroxyapatite preparation A, those numbers in the next fifth by random number 1 g of calcium as hydroxyapatite preparation B etc. Variable block size will ensure that the trial is less likely to be unbalanced in the event of early termination. The study pack allocation form will be filed in the CRF.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Type of endpoint/s
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/02/2011
Actual
1/07/2011
Date of last participant enrolment
Anticipated
30/04/2012
Actual
17/05/2012
Date of last data collection
Anticipated
Actual
Sample size
Target
100
Accrual to date
Final
Recruitment outside Australia
Country [1] 3097 0
New Zealand
State/province [1] 3097 0
Auckland

Funding & Sponsors
Funding source category [1] 258228 0
Commercial sector/Industry
Name [1] 258228 0
PharmaZen Limited
Country [1] 258228 0
New Zealand
Funding source category [2] 258229 0
Government body
Name [2] 258229 0
Health Research Council
Country [2] 258229 0
New Zealand
Funding source category [3] 258242 0
Government body
Name [3] 258242 0
Foundation for Research Science and Technology
Country [3] 258242 0
New Zealand
Primary sponsor type
University
Name
The University of Auckland
Address
Faculty of Medical and Health Sciences
University of Auckland
Private Bag 92019
Auckland 1142
New Zealand
Country
New Zealand
Secondary sponsor category [1] 263743 0
None
Name [1] 263743 0
Address [1] 263743 0
Country [1] 263743 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 260209 0
Northern X Regional Ethics Committee
Ethics committee address [1] 260209 0
Ministry of Health
Private Bag 92522
Wellesley Street
Auckland 1141
Ethics committee country [1] 260209 0
New Zealand
Date submitted for ethics approval [1] 260209 0
Approval date [1] 260209 0
14/01/2011
Ethics approval number [1] 260209 0

Summary
Brief summary
This is a randomised, single-blind, controlled 3-month study. One hundred healthy postmenopausal women will be randomised to one of the following five supplement preparations: 1g calcium as one of 2 hydroxyapatite preparations, 1g of calcium as citrate, 1g calcium as carbonate or a placebo. Participants will be seen twice over 3 months for clinical evaluation and laboratory, blood pressure and bone density measurement. Measurements will include serum biochemistry, haematology, markers of bone turnover and vascular calcification, and blood coagulation indices. The co-primary endpoints will be changes in blood calcium following the first dose of calcium, and markers of bone turnover at 3 months.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 32026 0
Prof Ian Reid
Address 32026 0
Faculty of Medical and Health Sciences University of Auckland Private Bag 92019 Auckland 1142
Country 32026 0
New Zealand
Phone 32026 0
+64 9 3737 599 ext 86259
Fax 32026 0
Email 32026 0
[email protected]
Contact person for public queries
Name 15273 0
Prof Professor Ian Reid
Address 15273 0
Faculty of Medical and Health Sciences
University of Auckland
Private Bag 92019
Auckland 1142
Country 15273 0
New Zealand
Phone 15273 0
+64 9 3737 599 ext 86259
Fax 15273 0
+64 9 308 2308
Email 15273 0
[email protected]
Contact person for scientific queries
Name 6201 0
Prof Professor Ian Reid
Address 6201 0
Faculty of Medical and Health Sciences
University of Auckland
Private Bag 92019
Auckland 1142
Country 6201 0
New Zealand
Phone 6201 0
+64 9 3737 599 ext 86259
Fax 6201 0
+64 9 308 2308
Email 6201 0
[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
SourceTitleYear of PublicationDOI
EmbaseAcute and 3-month effects of microcrystalline hydroxyapatite, calcium citrate and calcium carbonate on serum calcium and markers of bone turnover: A randomised controlled trial in postmenopausal women.2014https://dx.doi.org/10.1017/S0007114514002785
N.B. These documents automatically identified may not have been verified by the study sponsor.