Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617000697381
Ethics application status
Approved
Date submitted
3/03/2017
Date registered
16/05/2017
Date last updated
30/04/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Calcium supplements and 24-hour blood pressure
Scientific title
Calcium supplements and 24-hour blood pressure: a randomised, cross-over, placebo-controlled trial in postmenopausal women
Secondary ID [1] 291345 0
None
Universal Trial Number (UTN)
U1111-1193-7619
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Blood pressure 302328 0
Osteoporosis 302329 0
Condition category
Condition code
Cardiovascular 301913 301913 0 0
Hypertension
Musculoskeletal 301914 301914 0 0
Osteoporosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
0.5 grams of calcium as the citrate salt to be taken twice a day (once in the morning and once in the evening, 12 hours apart). The morning dose will taken at our clinic with a standardized breakfast meal consisting of toast with spread, fruit and tea or coffee. The evening dose will be taken by participants at home. The intervention will be administered as oral tablets. The intervention will be taken by all participants at the first or second visit (in a cross-over design) with at least a 7 day washout period between visits. Those that receive the intervention at the second visit will continue to receive the intervention for a further 4 weeks. Adherence to the intervention will be monitored by tablet return.
Intervention code [1] 297375 0
Treatment: Drugs
Comparator / control treatment
The control treatment will be a calcium-free placebo, taken twice a day (once in the morning and once in the evening, 12 hours apart). Methylcellulose will be administered as oral tablets, in an identical form to the intervention. The morning dose will taken at our clinic with a standardized breakfast meal consisting of toast with spread, fruit and tea or coffee. The evening dose will be taken by participants at home. The placebo will be taken by all participants at the first or second visit in a cross-over design. Those that receive the placebo at the second visit will continue to receive the placebo for a further 4 weeks. Adherence to the placebo will be monitored by tablet return.
Control group
Placebo

Outcomes
Primary outcome [1] 301343 0
Difference in the change from baseline in systolic blood pressure between day 1 of calcium supplementation and day 1 of placebo
Timepoint [1] 301343 0
Blood pressure will be measured every 30 minutes from 0900 to 2059 hours, and every 60 minutes from 2100 to 0859 hours using a 24-hour ambulatory blood pressure monitor. Mean blood pressure for each 2 hour block over 24 hours will be calculated. The primary time-point will be the difference in the change in systolic blood pressure 4-6 hours after the morning and evening dose of calcium and placebo at the first and second visits
Primary outcome [2] 301345 0
Difference in the change from baseline in diastolic blood pressure between day one of calcium supplementation and day one of placebo
Timepoint [2] 301345 0
Blood pressure will be measured every 30 minutes from 0900 to 2059 hours, and every 60 minutes from 2100 to 0859 hours using a 24-hour ambulatory blood pressure monitor. Mean blood pressure for each 2 hour block over 24 hours will be calculated. The primary time-point will be the difference in the change in diastolic blood pressure 4-6 hours after the morning and evening dose of calcium and placebo at the first and second visits
Secondary outcome [1] 332345 0
Difference in the change from baseline in systolic blood pressure between day 1 of calcium or placebo supplementation and after 4 weeks of continuous supplementation
Timepoint [1] 332345 0
Blood pressure will be measured every 30 minutes from 0900 to 2059 hours, and every 60 minutes from 2100 to 0859 hours using a 24-hour ambulatory blood pressure monitor. Mean blood pressure for each 2 hour block over 24 hours will be calculated. The secondary time-point will be 4-6 hours after the morning and evening dose of calcium at the second and third visits or placebo at the second and third visits
Secondary outcome [2] 332346 0
Difference in the change from baseline in diastolic blood pressure between day 1 of calcium or placebo supplementation and after 4 weeks of continuous supplementation
Timepoint [2] 332346 0
Blood pressure will be measured every 30 minutes from 0900 to 2059 hours, and every 60 minutes from 2100 to 0859 hours using a 24-hour ambulatory blood pressure monitor. Mean blood pressure for each 2 hour block over 24 hours will be calculated. The secondary time-point will be 4-6 hours after the morning and evening dose of calcium at the second and third visits or placebo at the second and third visits

Eligibility
Key inclusion criteria
Female
At least 5-years postmenopause
Age >55 years if age at menopause unknown
Minimum age
45 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Medical conditions
a. Hypertension (defined as either receiving BP-lowering medication for a prior diagnosis of hypertension or BP > 160 / 95)
b. Past history of coronary heart disease (MI or angina), cerebrovascular disease or peripheral vascular disease
c. Diabetes
d. Renal impairment (serum creatinine >0.15 mmol/L)
e. Chronic liver disease
f. Untreated hypothyroidism or hyperthyroidism
g. Concurrent major systemic illness, including malignancy
h. Active major gastrointestinal disease
i. Metabolic bone disease
j. Primary hyperparathyroidism
Medications
k. Calcium supplements (supplements containing doses of less than 100 mg/d of calcium may be continued during the study)
l. Calciferol supplements > 2000 IU/day
m. BP-lowering medications

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The allocation will be concealed through the use of numbered containers
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The order of receiving calcium or placebo at the first and second visits will be randomized using a computer-generated variable-block schedule.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Crossover
Other design features
Participants will receive calcium or placebo in a cross-over design at the first two visits of the study. Whichever treatment (calcium/placebo) participants are allocated to at their second visit they will continue to take for a further 4 weeks.
Phase
Phase 4
Type of endpoint/s
Safety
Statistical methods / analysis
We have used the within subject standard deviation for the pooled difference between the differences in calcium and placebo at each time point observed in two previous similar trials to determine the difference in the change in systolic and diastolic blood pressure that could be detected with 80% power at the 5% significance level. Allowing two participants lost to follow-up 50 participants would be adequately powered to detect differences of the changes in excess of 7.0mmHg systolic blood pressure and 3.4 mmHg diastolic.
The primary aim of this study is essentially descriptive. Initially the first and second visit 24 hour ambulatory blood pressure recordings will be plotted for each person to identify potential issues with the ambulatory blood pressure trace. All correct data will then be summarized and plotted as mean +/- SD change over time for each treatment arm. Then the two time points in the cross-over phase will be collapsed for each person. At each time point the difference between calcium and placebo will be calculated in the change in blood pressure from baseline and these mean differences of differences tested against a hypothesis of no difference in blood pressure using a mixed models approach to repeated measures controlling for repeated observations within the same participant over time. In sensitivity analysis the model will include an order effect. These analyses will include baseline blood pressure at the appropriate baseline as a covariate. An unstructured covariance matrix will be assumed for the within subject time and difference in treatment effects if possible.
Analyses will be performed in SAS (v9.4, SAS Institute Cary, NC, USA) with no adjustment for multiplicity. All tests will be two-tailed, P<0.05 will be considered significant and analysis will be according to the intention to treat principle.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
26/06/2017
Actual
17/01/2018
Date of last participant enrolment
Anticipated
16/11/2018
Actual
Date of last data collection
Anticipated
21/12/2018
Actual
Sample size
Target
50
Accrual to date
18
Final
Recruitment outside Australia
Country [1] 8710 0
New Zealand
State/province [1] 8710 0
Auckland

Funding & Sponsors
Funding source category [1] 295816 0
Charities/Societies/Foundations
Name [1] 295816 0
Auckland Medical Research Foundation
Country [1] 295816 0
New Zealand
Funding source category [2] 295818 0
Government body
Name [2] 295818 0
Health Research Council
Country [2] 295818 0
New Zealand
Primary sponsor type
Individual
Name
Sarah Bristow
Address
Faculty of Medical and Health Sciences
The University of Auckland
Private Bag 92019
Auckland 1142
New Zealand
Country
New Zealand
Secondary sponsor category [1] 294667 0
Individual
Name [1] 294667 0
Prof Ian Reid
Address [1] 294667 0
Faculty of Medical and Health Sciences
The University of Auckland
Private Bag 92019
Auckland 1142
New Zealand
Country [1] 294667 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297103 0
New Zealand Health and Disability Ethics Committee
Ethics committee address [1] 297103 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
Ethics committee country [1] 297103 0
New Zealand
Date submitted for ethics approval [1] 297103 0
02/05/2017
Approval date [1] 297103 0
19/05/2017
Ethics approval number [1] 297103 0
17/STH/72

Summary
Brief summary
Many people take calcium supplements to improve their bone health. However, studies have shown that people who take calcium supplements long-term have a slightly higher chance of having a heart attack. How calcium supplements increase the risk of a heart attack is not known, but it might be through an effect on our blood pressure. In a recent study we found that when women took a calcium supplement in the morning; their blood pressure was higher for the next several hours than when they took a placebo (a pill containing no calcium). If this increase in blood pressure is repeated every time a calcium supplement is taken long-term it could be what is causing the increased risk of a heart attack.

Calcium supplements are usually taken twice a day, in the morning and evening. The aim of this study is to find out how calcium supplements affect our blood pressure over a full day and night. To do this we need to measure blood pressure for 24 hours in women taking a morning and evening dose of a calcium supplement. We also want to find out if any effects of calcium supplements on blood pressure persist when people take them long-term. To do this we want to repeat the 24-hour measurement of blood pressure after women have taken a calcium supplement for 4 weeks.

We would like to enrol 50 healthy women who have been through the menopause for at least 5 years. This study will compare two treatments:
a. 0.5 grams of calcium as citrate (a calcium supplement) in the morning and evening
b. A placebo (pills containing no calcium) in the morning and evening

At each visit to our clinic participants will be given either the calcium supplement or the placebo along with a standardised breakfast meal. They will take their second dose of calcium or placebo pills that evening at home. During each visit to our clinic an ambulatory blood pressure monitor will be fitted on participants by study staff. This monitor will measure blood pressure every 30 minutes during the day and every 60 minutes during the night. Participants will be asked to keep an activity diary during the blood pressure monitoring periods.

The first and second visits will be separated by at least 7 days during which participants will not be required to take any supplements. The second and third visits will be separated by 4 weeks during which half of the participants in the study will take the calcium supplement in the morning and evening every day and half will take the placebo. Participants will not know whether they are taking calcium or placebo at any of your visits or during the 4 weeks of supplementation.

This study is awaiting ethical approval from the New Zealand Health and Disability Ethics Committee.

Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 72982 0
Dr Sarah Bristow
Address 72982 0
Faculty of Medical and Health Sciences
The University of Auckland
Private Bag 92019
Auckland 1142
Country 72982 0
New Zealand
Phone 72982 0
+64 9 923 3773
Fax 72982 0
Email 72982 0
[email protected]
Contact person for public queries
Name 72983 0
Dr Sarah Bristow
Address 72983 0
Faculty of Medical and Health Sciences
The University of Auckland
Private Bag 92019
Auckland 1142
Country 72983 0
New Zealand
Phone 72983 0
+64 9 923 3773
Fax 72983 0
Email 72983 0
[email protected]
Contact person for scientific queries
Name 72984 0
Dr Sarah Bristow
Address 72984 0
Faculty of Medical and Health Sciences
The University of Auckland
Private Bag 92019
Auckland 1142
Country 72984 0
New Zealand
Phone 72984 0
+6499233773
Fax 72984 0
Email 72984 0
[email protected]

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What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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