Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615001027505
Ethics application status
Approved
Date submitted
18/05/2015
Date registered
1/10/2015
Date last updated
10/02/2022
Date data sharing statement initially provided
10/02/2022
Date results information initially provided
10/02/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of Nitrates on Bone Density
Scientific title
Efficacy of nitrates on bone mineral density in postmenopausal women with osteopenia
Secondary ID [1] 286735 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteoporosis 295097 0
Condition category
Condition code
Musculoskeletal 295343 295343 0 0
Osteoporosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1, isosorbide mononitrate 20mg daily, immediate release, oral for 1 year then no intervention for 1 year
Arm 2, isosorbide mononitrate 30mg daily, sustained release, oral for 1 year then no intervention for 1 year
Arm 3, isosorbide mononitrate 60mg daily, sustained release, oral for 1 year then no intervention for 1 year
Arm 4, nitroglycerin 25 mg daily, transdermal for 1 year then no intervention for 1 year
Arm 5, nitroglycerin 50 mg daily, transdermal for 1 year then no intervention for 1 year

Treatment adherence will be monitored in the trial by count of tablet or patches returned at the 6 month and 1 year visits.
Intervention code [1] 291890 0
Treatment: Drugs
Intervention code [2] 292894 0
Prevention
Comparator / control treatment
Arm 6 Placebo, tablet daily for 1 year then no intervention for 1 year
Arm 7 Placebo, patch daily for 1 year then no intervention for 1 year
Control group
Placebo

Outcomes
Primary outcome [1] 295094 0
Change in lumbar spine bone mineral density assessed on DXA scans
Timepoint [1] 295094 0
1 year
Secondary outcome [1] 314752 0
Change in total hip bone mineral density assessed on DXA scans
Timepoint [1] 314752 0
1 year
Secondary outcome [2] 314753 0
Change in femoral neck bone mineral density assessed on DXA scans
Timepoint [2] 314753 0
1 year
Secondary outcome [3] 314754 0
Change in total body bone mineral density assessed on DXA scans
Timepoint [3] 314754 0
1 year
Secondary outcome [4] 314755 0
Change in markers of bone turnover (procollagen type-I N-terminal propeptide, P1NP, and Beta-C-terminal telopeptide of type I collagen, CTX, assessed using via serum assay)
Timepoint [4] 314755 0
1 year
Secondary outcome [5] 314757 0
Change in markers of bone turnover (procollagen type-I N-terminal propeptide, P1NP, and Beta-C-terminal telopeptide of type I collagen, CTX, assessed using via serum assay)
Timepoint [5] 314757 0
2 years
Secondary outcome [6] 314758 0
Change in lumbar spine bone mineral density assessed on DXA scans
Timepoint [6] 314758 0
2 years
Secondary outcome [7] 314759 0
Change in total hip bone mineral density assessed on DXA scans
Timepoint [7] 314759 0
2 years
Secondary outcome [8] 314760 0
Change in femoral neck bone mineral density assessed on DXA scans
Timepoint [8] 314760 0
2 years
Secondary outcome [9] 314761 0
Change in total body bone mineral density assessed on DXA scans
Timepoint [9] 314761 0
2 years

Eligibility
Key inclusion criteria
1. Postmenopausal women aged >55 years
2. Bone mineral density T score at the lumbar spine, femoral neck or total hip between -1 and -2.5
Minimum age
55 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Bone mineral density T score <-2.5 at the total hip, femoral neck or lumbar spine
2. Current use of nitrate agents, or phosphodiesterase-5 inhibitors
3. Concurrent major systemic illness including untreated hypothyroidism or hyperthyroidism, chronic liver disease, chronic renal failure, malignancy, and active major gastrointestinal disease
4. Known congenital heart disease or hypotension, systolic blood pressure < 100 mmHg
5. Metabolic bone disease
6. Previous fragility fracture of the hip or clinical spine fracture
7. Current or past use of bisphosphonate therapy within 12 months, or any past zoledronate use
8. Use of oral glucocorticoid drugs equivalent to an average dose of at least prednisone 2.5mg/day during the preceding 6 months
9. Use of hormone replacement therapy within 12 months
10. Known nitrate hypersensitivity

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)
Numbered containers
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation with blocks of varying size.
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
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
30/11/2015
Actual
20/09/2016
Date of last participant enrolment
Anticipated
Actual
30/10/2017
Date of last data collection
Anticipated
Actual
31/10/2018
Sample size
Target
240
Accrual to date
Final
240
Recruitment outside Australia
Country [1] 6886 0
New Zealand
State/province [1] 6886 0

Funding & Sponsors
Funding source category [1] 291287 0
Government body
Name [1] 291287 0
Health Research Council of New Zealand
Country [1] 291287 0
New Zealand
Primary sponsor type
University
Name
University of Auckland
Address
Private Bag 92019,
Auckland, 1142
New Zealand
Country
New Zealand
Secondary sponsor category [1] 289965 0
None
Name [1] 289965 0
Address [1] 289965 0
Country [1] 289965 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292853 0
Northern B Health and Disability Ethics Committee
Ethics committee address [1] 292853 0
Ministry of Health
Ethics Department
Freyberg Building
Reception – Ground Floor
20 Aitken Street
Wellington 6011
Ethics committee country [1] 292853 0
New Zealand
Date submitted for ethics approval [1] 292853 0
18/05/2015
Approval date [1] 292853 0
09/06/2015
Ethics approval number [1] 292853 0

Summary
Brief summary
Fractures occur in more than 50% of older women. Low bone density is a strong risk factor for fracture, but 80% of fractures occur in women with only mildly low bone density. Currently, there are no acceptable evidenced-based treatments for these women. Small studies have suggested that organic nitrates, which are commonly used to treat heart disease, might increase bone density. We plan to systematically investigate their effects on bone density. We will undertake a 2-year randomised, placebo-controlled trial of 5 different doses of organic nitrates in post-menopausal women with mildly low bone density. Participants will receive organic nitrates or inactive treatment for 1 year and then will be followed without treatment for 1 year. The main outcome is the change in bone density. If the treatment is effective, the study will provide the evidence base for a large trial to be conducted to test whether these agents can prevent fractures.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 57350 0
A/Prof Mark Bolland
Address 57350 0
Department of Medicine
University of Auckland
Private Bag 92019
Auckland 1142
Country 57350 0
New Zealand
Phone 57350 0
64 9 373 7599
Fax 57350 0
64 9 373 7677
Email 57350 0
m.bolland@auckland.ac.nz
Contact person for public queries
Name 57351 0
Dr Anne Horne
Address 57351 0
Department of Medicine
University of Auckland
Private Bag 92019
Auckland 1142
Country 57351 0
New Zealand
Phone 57351 0
64 9 373 7599
Fax 57351 0
64 9 373 7677
Email 57351 0
a.horne@auckland.ac.nz
Contact person for scientific queries
Name 57352 0
A/Prof Mark Bolland
Address 57352 0
Department of Medicine
University of Auckland
Private Bag 92019
Auckland 1142
Country 57352 0
New Zealand
Phone 57352 0
64 9 373 7599
Fax 57352 0
64 9 373 7677
Email 57352 0
m.bolland@auckland.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All requested data from the trial
When will data be available (start and end dates)?
From trial publication on pubmed (5/7/20) onwards with no end date
Available to whom?
Researchers upon reasonable request
Available for what types of analyses?
All analyses
How or where can data be obtained?
By contacting lead author by email (m.bolland@auckland.ac.nz)


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes Bolland MJ, House ME, Horne AM, Pinel V, Gamble GD... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseNitrates Do Not Affect Bone Density or Bone Turnover in Postmenopausal Women: A Randomized Controlled Trial.2020https://dx.doi.org/10.1002/jbmr.3982
N.B. These documents automatically identified may not have been verified by the study sponsor.