Nitrates and Bone Turnover; Nitrates and Bone Turnover Bisphosphonate Sub-Study

Phase 3

Completed

• Conditions: Osteoporosis
• Interventions: Drug: Nitrates (NABT Main trial); Other: Placebo

• Registration Number: NCT01387672
• Lead Sponsor: University of Toronto

Brief Summary

Purpose: NABT: To compare five widely available nitrate formulations: (1) 15 of nitroglycerin (NTG) ointment, (2) 0.3 mg and (3) 0.6 mg of sublingual NTG, (4) 20 mg of isosorbide mononitrate (an oral tablet), and (5) 160 mg of glycerol trinitrate (a patch), for their efficacy on markers of bone formation and resorption and for the incidence and severity of headache they cause.

Hypothesis: There is one ideal nitrate preparation which balances the clinical efficacy in bone remodeling against the common side effect of headache.

NABT-B: To determine if nitrates affect markers of bone formation (serum BALP and P1NP) and resorption (serum CTX and urine NTX) in women who have recently discontinued treatment with alendronate, risedronate or zoledronate.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-06-30
• Study First Submitted QC: 2011-07-01
• Study First Posted: 2011-07-04
• Study Start: 2011-09
• Primary Completion: 2014-12
• Study Completion: 2014-12
• Results First Submitted: 2015-02-17
• Status Verified: 2015-05
• Results First Submitted QC: 2015-05-06
• Last Update Submitted: 2015-05-06
• Results First Posted: 2015-05-08
• Last Update Posted: 2015-05-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 265

Inclusion Criteria

NABT:

• Women aged 50 years and older whose last menstrual period occurred at least 3 years ago
• Women without a uterus will be eligible after age 55

NABT-B:

• Women aged 50 years and older whose last menstrual period occurred at least 3 years ago
• Women without a uterus will be eligible after age 55
• Previously treated with alendronate but stopped within 2 years of study commencement; or previously treated with risedronate but stopped within 1 year of study commencement; or previously treated with zoledronate.

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Exclusion Criteria

NABT:

• A previous fracture of the hip, wrist, spine or ankle within the last 3 months; or a diagnosis of osteoporosis;
• A history of bone disorders such as hyperparathyroidism or Paget's disease;
• Treatment within 12 months of study entry with any agent that may influence bone metabolism including any hormone, anti-estrogen or raloxifene and prednisone (equivalent to 5 mg/d for 12 months or greater);
• Treatment with any antiresorptive agent, including alendronate, risedronate, etidronate or denosumab use for at least four weeks within the last three years;
• Previous treatment with intravenous zoledronate or parathyroid hormone;
• Current treatment with nitrates;
• A history of migraine headaches;
• A history of angina or cardiovascular disease;
• Inability to give informed consent;
• Hypersensitivity to nitroglycerin.

NABT-B:

• A previous fracture of the hip, wrist, spine or ankle; or a self-reported diagnosis of osteoporosis;
• A history of bone disorders such as hyperparathyroidism or Paget's disease;
• Treatment within 12 months of study entry with any agent that may influence bone metabolism including any hormone, anti-estrogen or raloxifene and prednisone (equivalent to 5 mg/d for 12 months or greater);
• Treatment with etidronate or denosumab use for at least four weeks within the last three years and any previous treatment with parathyroid hormone;
• Current treatment with nitrates;
• A history of migraine headaches;
• A history of angina or cardiovascular disease;
• Inability to give informed consent;
• Hypersensitivity to nitroglycerin.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Nitrostat 2	Nitrates (NABT Main trial)	Nitroglycerin 0.6mg Sublingual Tablet
Placebo	Placebo	Placebo Ointment
Nitrol	Nitrates (NABT Main trial)	Nitroglycerin Ointment 2% USP
Nitrostat 1	Nitrates (NABT Main trial)	Nitroglycerin 0.3mg Sublingual Tablet
Nitro-Dur	Nitrates (NABT Main trial)	Nitroglycerin Extended Release Patch 160mg
ISMO	Nitrates (NABT Main trial)	Isosorbide Mononitrate 20mg Oral Tablet

Primary Outcome Measures

Name	Time	Method
Bone Turnover Markers	3 months	Markers of Bone Formation: * Serum Procollagen type 1 amino- terminal propeptide (P1NP); * Serum Osteocalcin (OC); * Serum Bone-specific alkaline phosphatase (BALP); Markers of Bone Resorption: - Serum C-telopeptides of collagen cross-links (CTX)

Secondary Outcome Measures

Name	Time	Method
Headache	Run-in phase - 2 days	Severity of headaches. Subjects recorded the severity of headaches upon awakening every day during the run-in phase using a visual analogue scale (VAS). The scale is represented by a line (continuum) 10 cm long. Subjects were asked to make a vertical line along the continuum to indicate the severity of their headache each morning upon awakening. The score is recorded in cm from "0" to "10". A vertical line marked at "0" means no headache (score recorded = "0"), a vertical line marked at "10" means a terrible headache (score recorded = "10").

Trial Locations

Locations (1)

Women's College Research Institute/Women's College Hospital; 🇨🇦 Toronto, Ontario, Canada