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

NCT01387672 | Completed Phase 3 Results DMC

• 1 other identifier: 062011
• Study Type: interventional
• Target: 265
• Locations: 1 country
• Sites: 1

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.

Conditions

Osteoporosis

Keywords

postmenopausal; osteoporosis; bone turnover; nitrate; headache

Outcome Measures

Primary Outcomes (1)

• 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)

  3 months

Secondary Outcomes (1)

• Headache

  Run-in phase - 2 days

Study Arms (6)

Nitrol

ACTIVE COMPARATOR

Nitroglycerin Ointment 2% USP

Drug: Nitrates (NABT Main trial)

Nitro-Dur

ACTIVE COMPARATOR

Nitroglycerin Extended Release Patch 160mg

Drug: Nitrates (NABT Main trial)

Nitrostat 1

ACTIVE COMPARATOR

Nitroglycerin 0.3mg Sublingual Tablet

Drug: Nitrates (NABT Main trial)

Nitrostat 2

ACTIVE COMPARATOR

Nitroglycerin 0.6mg Sublingual Tablet

Drug: Nitrates (NABT Main trial)

ISMO

ACTIVE COMPARATOR

Isosorbide Mononitrate 20mg Oral Tablet

Drug: Nitrates (NABT Main trial)

Placebo

PLACEBO COMPARATOR

Placebo Ointment

Other: Placebo

Interventions

Nitrates (NABT Main trial) DRUG

nitroglycerin; isosorbide mononitrate

Also known as: NABT-B Sub-Study: Nitroglycerin Ointment 2%: 15mg of NTG ointment for a 3 month period

ISMO; Nitro-Dur; Nitrol; Nitrostat 1; Nitrostat 2

Placebo OTHER

Placebo ointment

Placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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);

Sponsors & Collaborators

• University of Toronto: lead
• The Physicians' Services Incorporated Foundation: collaborator
• California Pacific Medical Center: collaborator
• Sunnybrook Health Sciences Centre: collaborator
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

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

Toronto, Ontario, M5G 1N8, Canada

Location

Related Publications (6)

• 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.

  PMID: 21343579 BACKGROUND

• 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.

  PMID: 18800179 BACKGROUND

• 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.

  PMID: 15312252 BACKGROUND

• 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.

  PMID: 9797485 BACKGROUND

• 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.

  PMID: 19549739 BACKGROUND

• 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.

  PMID: 24010992 DERIVED

MeSH Terms

Conditions

Osteoporosis; Headache

Interventions

Nitrates

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Anions; Ions; Electrolytes; Inorganic Chemicals; Nitric Acid; Nitrogen Compounds; Organic Chemicals

Results Point of Contact

• Title: Dr. Sophie Jamal
• Organization: Womens' College Hospital

sophie.jamal@wchospital.ca

416-351-3732

Study Officials

• Sophie A Jamal, MD,PhD,FRCPC

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor/Endocrinologist

Study Record Dates

• First Submitted: June 30, 2011
• First Posted: July 4, 2011
• Study Start: September 1, 2011
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: May 8, 2015
• Results First Posted: May 8, 2015

Record last verified: 2015-05

Locations

CA (1)