ANZCTR - Registration

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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 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]

Nil

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Osteoporosis

Condition category

Condition code

Musculoskeletal

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]

Treatment: Drugs

Intervention code [2]

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]

Change in lumbar spine bone mineral density assessed on DXA scans

Timepoint [1]

1 year

Secondary outcome [1]

Change in total hip bone mineral density assessed on DXA scans

Timepoint [1]

1 year

Secondary outcome [2]

Change in femoral neck bone mineral density assessed on DXA scans

Timepoint [2]

1 year

Secondary outcome [3]

Change in total body bone mineral density assessed on DXA scans

Timepoint [3]

1 year

Secondary outcome [4]

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]

1 year

Secondary outcome [5]

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]

2 years

Secondary outcome [6]

Change in lumbar spine bone mineral density assessed on DXA scans

Timepoint [6]

2 years

Secondary outcome [7]

Change in total hip bone mineral density assessed on DXA scans

Timepoint [7]

2 years

Secondary outcome [8]

Change in femoral neck bone mineral density assessed on DXA scans

Timepoint [8]

2 years

Secondary outcome [9]

Change in total body bone mineral density assessed on DXA scans

Timepoint [9]

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?

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]

New Zealand

State/province [1]

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

Health Research Council of New Zealand

Address [1]

PO Box 5541,
Wellesley Street,
Auckland 1141
New Zealand

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Northern B Health and Disability Ethics Committee

Ethics committee address [1]

Ministry of Health
Ethics Department
Freyberg Building
Reception – Ground Floor
20 Aitken Street
Wellington 6011

Ethics committee country [1]

New Zealand

Date submitted for ethics approval [1]

18/05/2015

Approval date [1]

09/06/2015

Ethics approval number [1]

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

A/Prof Mark Bolland

Address

Department of Medicine
University of Auckland
Private Bag 92019
Auckland 1142

Country

New Zealand

Phone

64 9 373 7599

Fax

64 9 373 7677

m.bolland@auckland.ac.nz

Contact person for public queries

Name

Anne Horne

Address

Department of Medicine
University of Auckland
Private Bag 92019
Auckland 1142

Country

New Zealand

Phone

64 9 373 7599

Fax

64 9 373 7677

a.horne@auckland.ac.nz

Contact person for scientific queries

Name

Mark Bolland

Address

Department of Medicine
University of Auckland
Private Bag 92019
Auckland 1142

Country

New Zealand

Phone

64 9 373 7599

Fax

64 9 373 7677

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

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Nitrates Do Not Affect Bone Density or Bone Turnover in Postmenopausal Women: A Randomized Controlled Trial.	2020	https://dx.doi.org/10.1002/jbmr.3982

N.B. These documents automatically identified may not have been verified by the study sponsor.

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Documents added manually

Documents added automatically