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

May 6, 2015 updated by: Sophie Jamal, University of Toronto

Nitrates and Bone Turnover (NABT): Trial to Select the Best Nitrate Preparation

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

265

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 1N8
        • Women's College Research Institute/Women's College Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Nitrol
Nitroglycerin Ointment 2% USP
Drug: Nitrates (NABT Main trial)
nitroglycerin; isosorbide mononitrate
Other Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bone Turnover Markers
Time Frame: 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)
3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Headache
Time Frame: 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").
Run-in phase - 2 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Toronto

Collaborators

Sunnybrook Health Sciences Centre
Canadian Institutes of Health Research (CIHR)
The Physicians' Services Incorporated Foundation
California Pacific Medical Center

Investigators

  • Principal Investigator: Sophie A Jamal, MD,PhD,FRCPC, Women's College Research Institute/Women's College Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2011

Primary Completion (Actual)

December 1, 2014

Study Completion (Actual)

December 1, 2014

Study Registration Dates

First Submitted

June 30, 2011

First Submitted That Met QC Criteria

July 1, 2011

First Posted (Estimate)

July 4, 2011

Study Record Updates

Last Update Posted (Estimate)

May 8, 2015

Last Update Submitted That Met QC Criteria

May 6, 2015

Last Verified

May 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 062011

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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