Nitrates and Bone Turnover; Nitrates and Bone Turnover Bisphosphonate Sub-Study (NABT;NABT-B)

University of Toronto

Status and phase: Completed; Phase 3

Conditions: Osteoporosis

Treatments: Drug: Nitrates (NABT Main trial); Other: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT01387672

062011

Details and patient eligibility

About

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.

Enrollment: 265 patients

Sex: Female

Ages: 50+ years old

Volunteers: Accepts Healthy Volunteers

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.

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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265 participants in 6 patient groups, including a placebo group

Nitrol

Active Comparator group

Description:

Nitroglycerin Ointment 2% USP

Treatment:

Drug: Nitrates (NABT Main trial)

Nitro-Dur

Active Comparator group

Description:

Nitroglycerin Extended Release Patch 160mg

Treatment:

Drug: Nitrates (NABT Main trial)

Nitrostat 1

Active Comparator group

Description:

Nitroglycerin 0.3mg Sublingual Tablet

Treatment:

Drug: Nitrates (NABT Main trial)

Nitrostat 2

Active Comparator group

Description:

Nitroglycerin 0.6mg Sublingual Tablet

Treatment:

Drug: Nitrates (NABT Main trial)

ISMO

Active Comparator group

Description:

Isosorbide Mononitrate 20mg Oral Tablet

Treatment:

Drug: Nitrates (NABT Main trial)

Placebo

Placebo Comparator group

Description:

Placebo Ointment

Treatment:

Other: Placebo