We propose to test the efficacy and safety of daily nitroglycerin for reduction in risk of fractures in a year randomized trial (Nitric Oxide Fracture Trial - aka 'NO Fracture Trial'). Our primary aim for the trial is to test the hypothesis that dail nitrates, compared with alendronate 70 mg once weekly reduces the risk of nonvertebral fracture in women at high risk for such fractures. The secondary aims are to test the hypotheses that, compared with alendronate, daily nitrate administration: (a) Is not inferior to alendronate fr reduction in risk of vertebral fracture;(b) reduces the risk of clinical fractures;and (c) producs greater increases in bone mineral density (BMD) at femoral neck and lumbar spine. Lastly, we will compare the risk of adverse events between nitroglycerin and alendronate. The goal in the planning phase is to develop an NIH proposal for funding for the NO Fracture Trial.
The specific aims for the planning phase are: (1) decide the formulation and dose of the nitrate treatment;(2) finalize the sample size and enrollment criteria, and plan recruitment strategies;(3) identify and engage clinical sites capable of on-time recruitment of enough participants;(4) complete the study protocol, operations manuals, data collection forms and plans for data management;(5) develop the plan for safety and data monitoring and a data safety monitoring board;(6) obtain the necessary regulatory approvals for the trial;(7) develop the study budget and strategies to minimize the cost of the trial;and (8) write and submit the proposal for the NO Fracture Trial. This planning phase will lead to a well-reasoned design, efficient and feasible plan and proposal for the NO Fracture trial. We expect the NO Fracture Trial to demonstrate that the use of daily nitrate safely reduces the risk of nonvertebral fractures more than alendronate. If successful, findings from this trial would lead to world-wide use of this inexpensive medicine with greater reduction in the personal and social burden of fractures than achievable with current therapy.

Public Health Relevance

We are proposing a planning grant for a trial to test the efficacy and safety of daily nitroglycerin for reduction in risk of fractures in a year randomized trial (Nitric Oxide (NO) Fracture Trial). Planning grant activities will include: the development o study documents (protocol, operations manual and forms), budgets and data management and data safety monitoring plans;identification of clinical sites and DSMB members;determination of regulatory requirements;and preparation and submission of a proposal for the NO Fracture Trial.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Clinical Planning Grant Cooperative Agreement (U34)
Project #
1U34AR066566-01
Application #
8753948
Study Section
Special Emphasis Panel (ZAR1-HL (M1))
Program Officer
Chen, Faye H
Project Start
2014-08-25
Project End
2016-06-30
Budget Start
2014-08-25
Budget End
2015-06-30
Support Year
1
Fiscal Year
2014
Total Cost
$333,446
Indirect Cost
$106,355
Name
California Pacific Medical Center Research Institute
Department
Type
DUNS #
071882724
City
San Francisco
State
CA
Country
United States
Zip Code
94107