Nitrates and bone turnover (NABT) - trial to select the best nitrate preparation:
study protocol for a randomized controlled trial.
Author(s): Bucur RC(1), Reid LS, Hamilton CJ, Cummings SR, Jamal SA.
Affiliation(s): Author information:
(1)Women's College Research Institute and Department of Medicine, Women's College
Hospital, The University of Toronto, Toronto, Ontario, Canada.
sophie.jamal@utoronto.ca.
Publication date & source: 2013, Trials. , 14:284
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.
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