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

This study has been completed.
Sponsor:
Collaborators:
The Physicians' Services Incorporated Foundation
California Pacific Medical Center
Sunnybrook Health Sciences Centre
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Sophie Jamal, University of Toronto
ClinicalTrials.gov Identifier:
NCT01387672
First received: June 30, 2011
Last updated: May 6, 2015
Last verified: May 2015
  Purpose

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.


Condition Intervention Phase
Osteoporosis
Drug: Nitrates (NABT Main trial)
Other: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Nitrates and Bone Turnover (NABT): Trial to Select the Best Nitrate Preparation

Resource links provided by NLM:


Further study details as provided by University of Toronto:

Primary Outcome Measures:
  • Bone Turnover Markers [ Time Frame: 3 months ] [ Designated as safety issue: No ]

    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:
  • Headache [ Time Frame: Run-in phase - 2 days ] [ Designated as safety issue: No ]
    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").


Enrollment: 265
Study Start Date: September 2011
Study Completion Date: December 2014
Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Nitrol
Nitroglycerin Ointment 2% USP
Drug: Nitrates (NABT Main trial)
nitroglycerin; isosorbide mononitrate
Other Name: NABT-B Sub-Study: Nitroglycerin Ointment 2%: 15mg of NTG ointment for a 3 month period
Active Comparator: Nitro-Dur
Nitroglycerin Extended Release Patch 160mg
Drug: Nitrates (NABT Main trial)
nitroglycerin; isosorbide mononitrate
Other Name: NABT-B Sub-Study: Nitroglycerin Ointment 2%: 15mg of NTG ointment for a 3 month period
Active Comparator: Nitrostat 1
Nitroglycerin 0.3mg Sublingual Tablet
Drug: Nitrates (NABT Main trial)
nitroglycerin; isosorbide mononitrate
Other Name: NABT-B Sub-Study: Nitroglycerin Ointment 2%: 15mg of NTG ointment for a 3 month period
Active Comparator: Nitrostat 2
Nitroglycerin 0.6mg Sublingual Tablet
Drug: Nitrates (NABT Main trial)
nitroglycerin; isosorbide mononitrate
Other Name: NABT-B Sub-Study: Nitroglycerin Ointment 2%: 15mg of NTG ointment for a 3 month period
Active Comparator: ISMO
Isosorbide Mononitrate 20mg Oral Tablet
Drug: Nitrates (NABT Main trial)
nitroglycerin; isosorbide mononitrate
Other Name: NABT-B Sub-Study: Nitroglycerin Ointment 2%: 15mg of NTG ointment for a 3 month period
Placebo Comparator: Placebo
Placebo Ointment
Other: Placebo
Placebo ointment

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01387672

Locations
Canada, Ontario
Women's College Research Institute/Women's College Hospital
Toronto, Ontario, Canada, M5G 1N8
Sponsors and Collaborators
University of Toronto
The Physicians' Services Incorporated Foundation
California Pacific Medical Center
Sunnybrook Health Sciences Centre
Canadian Institutes of Health Research (CIHR)
Investigators
Principal Investigator: Sophie A Jamal, MD,PhD,FRCPC Women's College Research Institute/Women's College Hospital
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sophie Jamal, Associate Professor/Endocrinologist, University of Toronto
ClinicalTrials.gov Identifier: NCT01387672     History of Changes
Other Study ID Numbers: 062011
Study First Received: June 30, 2011
Results First Received: February 17, 2015
Last Updated: May 6, 2015
Health Authority: Canada: Health Canada

Keywords provided by University of Toronto:
postmenopausal
osteoporosis
bone turnover
nitrate
headache

Additional relevant MeSH terms:
Osteoporosis
Bone Diseases
Bone Diseases, Metabolic
Musculoskeletal Diseases
Nitroglycerin
Cardiovascular Agents
Pharmacologic Actions
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on August 31, 2015