OsteoporosisPhase 3NABT;NABT-BNCT01387672

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

A Phase 3 study testing Nitrates (NABT Main trial) in people with Osteoporosis, run by University of Toronto at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 50 years and older, women onlyHealthy volunteers can take part
Conditions the study is for: Osteoporosis
What is being tested?: Nitrates (NABT Main trial)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 265 participants
Where: 1 siteCanada
Study dates: Sep 2011to Dec 2014
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 50 years and older
Women only
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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.

Who cannot join

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;

Show all 21Show fewer

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 locations and contacts

1 site in 1 country.

Canada1 site

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

Other trials in Canada

About this study

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

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.

Conditions: Osteoporosis
Being tested: Nitrates (NABT Main trial), Placebo
Keywords: postmenopausal, osteoporosis, bone turnover, nitrate, headache
Medical subject headings: Osteoporosis, Headache

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Nitrates (NABT Main trial)Drug
Also called NABT-B Sub-Study: Nitroglycerin Ointment 2%: 15mg of NTG ointment for a 3 month period
nitroglycerin; isosorbide mononitrate
PlaceboOther
Placebo ointment

Study groups in NCT01387672
Study group	Role	What they receive
Nitrol	Active comparator	Nitroglycerin Ointment 2% USP Receives: Drug: Nitrates (NABT Main trial)
Nitro-Dur	Active comparator	Nitroglycerin Extended Release Patch 160mg Receives: Drug: Nitrates (NABT Main trial)
Nitrostat 1	Active comparator	Nitroglycerin 0.3mg Sublingual Tablet Receives: Drug: Nitrates (NABT Main trial)
Nitrostat 2	Active comparator	Nitroglycerin 0.6mg Sublingual Tablet Receives: Drug: Nitrates (NABT Main trial)
ISMO	Active comparator	Isosorbide Mononitrate 20mg Oral Tablet Receives: Drug: Nitrates (NABT Main trial)
Placebo	Placebo comparator	Placebo Ointment Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Bone Turnover Markers
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)
Measured: 3 months

Secondary outcomes (1)

Headache
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").
Measured: Run-in phase - 2 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2011Dec 2014

First posted4 Jul 2011 (estimated)
Study startSep 2011
Primary completionDec 2014
Study completionDec 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (6)Papers the sponsor has linked to this study.
Other trials for OsteoporosisStudies of the same condition, open and under way.
More trials run by University of TorontoThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 265 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01387672
Sponsor's protocol ID: 062011
Acronym: NABT;NABT-B
Status last verified: May 2015
First submitted: 30 Jun 2011
Last updated: 8 May 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Jamal SA, Hamilton CJ, Eastell R, Cummings SR. Effect of nitroglycerin ointment on bone density and strength in postmenopausal women: a randomized trial. JAMA. 2011 Feb 23;305(8):800-7. doi: 10.1001/jama.2011.176.
PubMed 21343579
Jamal SA, Goltzman D, Hanley DA, Papaioannou A, Prior JC, Josse RG. Nitrate use and changes in bone mineral density: the Canadian Multicentre Osteoporosis Study. Osteoporos Int. 2009 May;20(5):737-44. doi: 10.1007/s00198-008-0727-7. Epub 2008 Sep 18.
PubMed 18800179
Jamal SA, Cummings SR, Hawker GA. Isosorbide mononitrate increases bone formation and decreases bone resorption in postmenopausal women: a randomized trial. J Bone Miner Res. 2004 Sep;19(9):1512-7. doi: 10.1359/JBMR.040716. Epub 2004 Jul 26.
PubMed 15312252
Jamal SA, Browner WS, Bauer DC, Cummings SR. Intermittent use of nitrates increases bone mineral density: the study of osteoporotic fractures. J Bone Miner Res. 1998 Nov;13(11):1755-9. doi: 10.1359/jbmr.1998.13.11.1755.
PubMed 9797485
Wimalawansa SJ, Grimes JP, Wilson AC, Hoover DR. Transdermal nitroglycerin therapy may not prevent early postmenopausal bone loss. J Clin Endocrinol Metab. 2009 Sep;94(9):3356-64. doi: 10.1210/jc.2008-2225. Epub 2009 Jun 23.
PubMed 19549739
Bucur RC, Reid LS, Hamilton CJ, Cummings SR, Jamal SA. Nitrates and bone turnover (NABT) - trial to select the best nitrate preparation: study protocol for a randomized controlled trial. Trials. 2013 Sep 8;14:284. doi: 10.1186/1745-6215-14-284.
PubMed 24010992

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 8 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Nitrates and Bone Turnover (NABT): Trial to Select the Best Nitrate Preparation
ClinicalTrials.gov ID: NCT01387672
Acronym / sponsor ID: NABT;NABT-B / 062011
Conditions: Osteoporosis
Keywords: postmenopausal, osteoporosis, bone turnover, nitrate, headache
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 265 participants (actual)
Lead sponsor: University of TorontoUniversity, hospital or other
Collaborators: The Physicians' Services Incorporated Foundation, California Pacific Medical Center, Sunnybrook Health Sciences Centre, Canadian Institutes of Health Research (CIHR)
Study start: Sep 2011
Primary completion: Dec 2014 (actual)
Study completion: Dec 2014 (actual)
First posted: 4 Jul 2011 (estimated)
Results: Posted 8 May 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 6

Arm	Type	Receives
Nitrol	Active comparator	Drug: Nitrates (NABT Main trial)Nitroglycerin Ointment 2% USP
Nitro-Dur	Active comparator	Drug: Nitrates (NABT Main trial)Nitroglycerin Extended Release Patch 160mg
Nitrostat 1	Active comparator	Drug: Nitrates (NABT Main trial)Nitroglycerin 0.3mg Sublingual Tablet
Nitrostat 2	Active comparator	Drug: Nitrates (NABT Main trial)Nitroglycerin 0.6mg Sublingual Tablet
ISMO	Active comparator	Drug: Nitrates (NABT Main trial)Isosorbide Mononitrate 20mg Oral Tablet
Placebo	Placebo comparator	Other: PlaceboPlacebo Ointment

Who may qualify

Ages: 50 years and older
Sex: Female only
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

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
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.

Key exclusion criteria (21 listed)

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;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Nitrates (NABT Main trial)Also: NABT-B Sub-Study: Nitroglycerin Ointment 2%: 15mg of NTG ointment for a 3 month periodnitroglycerin; isosorbide mononitrate	Drug	ISMO, Nitro-Dur, Nitrol, Nitrostat 1, Nitrostat 2
PlaceboPlacebo ointment	Other	Placebo

Primary outcome

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)

1 secondary outcome

Headache
Time frame: Run-in phase - 2 days

Results and safety

Results posted to the registry on 8 May 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
ISMO - Treatment Arm 1	39	32
Patch (Nitro-Dur) - Treatment Arm 2	38	31
Ointment (Nitrol) - Treatment Arm 3	38	33
0.3 Sublingual (Nitrostat 1) - Treatment Arm 4	39	35
0.6 Sublingual (Nitrostat 2) - Treatment Arm 5	38	34
Placebo Ointment - Treatment Arm 6	37	37

Primary outcome: Bone Turnover Markers

Time frame: 3 months. Mean (Standard Deviation). Unit: Percent change from baseline

Measure	ISMO - Treatment Arm 1 n = 32	Patch (Nitro-Dur) - Treatment Arm 2 n = 31	Ointment (Nitrol) - Treatment Arm 3 n = 32	0.3 Sublingual (Nitrostat 1) - Treatment Arm 4 n = 35	0.6 Sublingual (Nitrostat 2) - Treatment Arm 5 n = 34	Placebo Ointment - Treatment Arm 6 n = 37
P1NP	-4.627 (16.191)	-0.405 (20.289)	-4.297 (16.236)	-6.126 (16.093)	2.941 (36.843)	-1.635 (16.749)
OC	-3.244 (12.049)	3.796 (33.601)	-4.481 (14.823)	1.046 (21.818)	1.033 (17.931)	4.247 (22.088)
BALP	-5.023 (11.824)	-0.541 (20.738)	-7.426 (11.056)	-7.000 (19.011)	-3.686 (17.435)	-1.648 (21.523)
CTX	-5.844 (26.084)	-1.025 (32.163)	-9.699 (27.299)	-0.666 (37.945)	-1.380 (52.248)	-1.783 (28.063)

Population analysed: One subject from the Treatment Arm 3 had outlier bone turnover markers values and was excluded from the analysis. Total number of subjects analyzed in Treatment Arm 3 was therefore 32.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: The Adverse Events are reported for the 3 months treatment phase of the study, once the patients were randomized to a specific treatment arm (ISMO - Arm 1; Patch - Arm 2; Ointment - Arm 3; 0.3 Sublingual - Arm 4; 0.6 Sublingual - Arm 5 or Placebo - Arm 6). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
ISMO - Treatment Arm 1	0 of 39 (0%)	17 of 39 (43.6%)	Not reported
Patch (Nitro-Dur) - Treatment Arm 2	0 of 38 (0%)	21 of 38 (55.3%)	Not reported
Ointment (Nitrol) - Treatment Arm 3	0 of 38 (0%)	17 of 38 (44.7%)	Not reported
0.3 Sublingual (Nitrostat 1) - Treatment Arm 4	1 of 39 (2.6%)	10 of 39 (25.6%)	Not reported
0.6 Sublingual (Nitrostat 2) - Treatment Arm 5	1 of 38 (2.6%)	12 of 38 (31.6%)	Not reported
Placebo Ointment- Treatment Arm 6	0 of 37 (0%)	6 of 37 (16.2%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 21343579Jamal SA, Hamilton CJ, Eastell R, Cummings SR. Effect of nitroglycerin ointment on bone density and strength in postmenopausal women: a randomized trial. JAMA. 2011 Feb 23;305(8):800-7. doi: 10.1001/jama.2011.176.
Background: PubMed 18800179Jamal SA, Goltzman D, Hanley DA, Papaioannou A, Prior JC, Josse RG. Nitrate use and changes in bone mineral density: the Canadian Multicentre Osteoporosis Study. Osteoporos Int. 2009 May;20(5):737-44. doi: 10.1007/s00198-008-0727-7. Epub 2008 Sep 18.
Background: PubMed 15312252Jamal SA, Cummings SR, Hawker GA. Isosorbide mononitrate increases bone formation and decreases bone resorption in postmenopausal women: a randomized trial. J Bone Miner Res. 2004 Sep;19(9):1512-7. doi: 10.1359/JBMR.040716. Epub 2004 Jul 26.
Background: PubMed 9797485Jamal SA, Browner WS, Bauer DC, Cummings SR. Intermittent use of nitrates increases bone mineral density: the study of osteoporotic fractures. J Bone Miner Res. 1998 Nov;13(11):1755-9. doi: 10.1359/jbmr.1998.13.11.1755.
Background: PubMed 19549739Wimalawansa SJ, Grimes JP, Wilson AC, Hoover DR. Transdermal nitroglycerin therapy may not prevent early postmenopausal bone loss. J Clin Endocrinol Metab. 2009 Sep;94(9):3356-64. doi: 10.1210/jc.2008-2225. Epub 2009 Jun 23.
Derived from this study: PubMed 24010992Bucur RC, Reid LS, Hamilton CJ, Cummings SR, Jamal SA. Nitrates and bone turnover (NABT) - trial to select the best nitrate preparation: study protocol for a randomized controlled trial. Trials. 2013 Sep 8;14:284. doi: 10.1186/1745-6215-14-284.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Sophie A Jamal, MD,PhD,FRCPC principal investigator

Women's College Research Institute/Women's College Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Nitrates (NABT Main trial) in people with Osteoporosis, run by University of Toronto at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 May 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 May 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Bone Turnover Markers (time frame: 3 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01387672, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2015.