Nitrates and bone turnover (NABT) - trial to select the best nitrate preparation: study protocol for a randomized controlled trial

Trials

Sophie A Jamal⁴  Steven R Cummings²  Celeste J Hamilton³  Lauren S Reid¹  Roxana C Bucur¹ 

[1] Women’s College Research Institute, Women’s College Hospital, Toronto, Ontario, Canada;San Francisco Coordinating Centre, San Francisco, CA, USA;Women’s College Research Institute, Women’s College Hospital, The University of Toronto, Toronto, Ontario, Canada;Women’s College Research Institute and Department of Medicine, Women’s College Hospital, The University of Toronto, Toronto, Ontario, Canada

关键词: Postmenopausal osteoporosis;    Bone turnover markers;    Organic nitrates;   

Others  :  1093102
DOI  :  10.1186/1745-6215-14-284

 received in 2012-09-17, accepted in 2013-08-21,  发布年份 2013

【 摘 要 】

Background

Organic nitrates uncouple bone turnover, improve bone mineral density, and improve trabecular and cortical components of bone. These changes in turnover, strength and geometry may translate into an important reduction in fractures. However, before proceeding with a large fracture trial, there is a need to identify the nitrate formulation that has both the greatest efficacy (with regards to bone turnover markers) and gives the fewest headaches. Ascertaining which nitrate formulation this may be is the purpose of the current study.

Methods and design

This will be an open-label randomized, controlled trial conducted at Women’s College Hospital comparing five formulations of nitrates for their effects on bone turnover markers and headache. We will recruit postmenopausal women age 50 years or older with no contraindications to nitroglycerin. Our trial will consist of a run-in phase and a treatment phase. We will enroll 420 women in the run-in phase, each to receive all of the 5 potential treatments in random order for 2 days, each with a 2-day washout period between treatments. Those who tolerate all formulations will enter the 12-week treatment phase and be randomly assigned to one of five groups: 0.3 mg sublingual nitroglycerin tablet, 0.6 mg of the sublingual tablet, a 20 mg tablet of isosorbide mononitrate, a 160 mg nitroglycerin transdermal patch (used for 8 h), and 15 mg of nitroglycerin ointment as used in a previous trial by our group. We will continue enrolment until we have randomized 210 women or 35 women per group. Concentrations of bone formation (bone-specific alkaline phosphatase and procollagen type I N-terminal propeptide) and bone resorption (C-telopeptides of collagen crosslinks and N-terminal crosslinks of collagen) agents will be measured in samples taken at study entry (the start of the run in phase) and 12 weeks. Subjects will record the frequency and severity of headaches daily during the run-in phase and then monthly after that. We will use the ‘multiple comparisons with the best’ approach for data analyses, as this strategy allows practical considerations of ease of use and tolerability to guide selection of the preparation for future studies.

Discussion

Data from this protocol will be used to develop a randomized, controlled trial of nitrates to prevent osteoporotic fractures.

Trial registration

ClinicalTrials.gov Identifier: NCT01387672. Controlled-Trials.com: ISRCTN08860742.

【 授权许可】

   
2013 Bucur et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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