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

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ClinicalTrials.gov Identifier: NCT01387672
Recruitment Status : Completed
First Posted : July 4, 2011
Results First Posted : May 8, 2015
Last Update Posted : May 8, 2015
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

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Prevention
Condition Osteoporosis
Interventions Drug: Nitrates (NABT Main trial)
Other: Placebo
Enrollment 265
Recruitment Details  
Pre-assignment Details Initial run-in period-subjects received, in random order, each of the 5 nitrate formulations for 2 days with a 2 day wash out period between formulations. There were 265 subjects enrolled in the run-in phase of the study. Out of those, 229 subjects entered the treatment phase of the study, where they were randomized to one of the 6 treatment arms.
Arm/Group Title ISMO - Treatment Arm 1 Patch (Nitro-Dur) - Treatment Arm 2 Ointment (Nitrol) - Treatment Arm 3 0.3 Sublingual (Nitrostat 1) - Treatment Arm 4 0.6 Sublingual (Nitrostat 2) - Treatment Arm 5 Placebo Ointment - Treatment Arm 6
Hide Arm/Group Description

Isosorbide Mononitrate 20mg Oral Tablet

Nitrates (NABT Main trial)

Nitroglycerin Extended Release Patch 160mg

Nitrates (NABT Main trial)

Nitroglycerin Ointment 2% USP

Nitrates (NABT Main trial)

Nitroglycerin 0.3mg Sublingual Tablet

Nitrates (NABT Main trial)

Nitroglycerin 0.6mg Sublingual Tablet

Nitrates (NABT Main trial)

Placebo Ointment

Nitrates (NABT Main trial)

Period Title: Overall Study
Started 39 38 38 39 38 37
Completed 32 31 33 35 34 37
Not Completed 7 7 5 4 4 0
Arm/Group Title ISMO - Treatment Arm 1 Patch (Nitro-Dur) - Treatment Arm 2 Ointment (Nitrol) - Treatment Arm 3 0.3 Sublingual (Nitrostat 1) - Treatment Arm 4 0.6 Sublingual (Nitrostat 2) - Treatment Arm 5 Placebo Ointment - Treatment Arm 6 Total
Hide Arm/Group Description

Isosorbide Mononitrate 20mg Oral Tablet

Nitrates (NABT Main trial)

Nitroglycerin Extended Release Patch 160mg

Nitrates (NABT Main trial)

Nitroglycerin Ointment 2% USP

Nitrates (NABT Main trial)

Nitroglycerin 0.3mg Sublingual Tablet

Nitrates (NABT Main trial)

Nitroglycerin 0.6mg Sublingual Tablet

Nitrates (NABT Main trial)

Placebo Ointment

Placebo: Placebo ointment Nitrates (NABT Main trial)

Total of all reporting groups
Overall Number of Baseline Participants 39 38 38 39 38 37 229
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 39 participants 38 participants 38 participants 39 participants 38 participants 37 participants 229 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
19
  48.7%
21
  55.3%
20
  52.6%
23
  59.0%
23
  60.5%
20
  54.1%
126
  55.0%
>=65 years
20
  51.3%
17
  44.7%
18
  47.4%
16
  41.0%
15
  39.5%
17
  45.9%
103
  45.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 39 participants 38 participants 38 participants 39 participants 38 participants 37 participants 229 participants
Female
39
 100.0%
38
 100.0%
38
 100.0%
39
 100.0%
38
 100.0%
37
 100.0%
229
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Canada Number Analyzed 39 participants 38 participants 38 participants 39 participants 38 participants 37 participants 229 participants
39 38 38 39 38 37 229
1.Primary Outcome
Title Bone Turnover Markers
Hide Description

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)

Time Frame 3 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title ISMO - Treatment Arm 1 Patch (Nitro-Dur) - Treatment Arm 2 Ointment (Nitrol) - Treatment Arm 3 0.3 Sublingual (Nitrostat 1) - Treatment Arm 4 0.6 Sublingual (Nitrostat 2) - Treatment Arm 5 Placebo Ointment - Treatment Arm 6
Hide Arm/Group Description:

Isosorbide Mononitrate 20mg Oral Tablet

Nitrates (NABT Main trial)

Nitroglycerin Extended Release Patch 160mg

Nitrates (NABT Main trial)

Nitroglycerin Ointment 2% USP

Nitrates (NABT Main trial)

Nitroglycerin 0.3mg Sublingual Tablet

Nitrates (NABT Main trial)

Nitroglycerin 0.6mg Sublingual Tablet

Nitrates (NABT Main trial)

Placebo Ointment

Placebo: Placebo ointment Nitrates (NABT Main trial)

Overall Number of Participants Analyzed 32 31 32 35 34 37
Mean (Standard Deviation)
Unit of Measure: Percent change from baseline
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)
2.Secondary Outcome
Title Headache
Hide Description 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").
Time Frame Run-in phase - 2 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The mean headache score considering all subjects in each of the treatment/formulation group was calculated.
Arm/Group Title Run-in Phase
Hide Arm/Group Description:
During the run-in phase subjects received, in random order, each of the 5 nitrate formulations for 2 days with a 2 day wash out period between formulations. The severity of headaches was recorded, by subjects, upon awakening, every day during the run in phase using a visual analog scale (VAS).
Overall Number of Participants Analyzed 238
Mean (Standard Deviation)
Unit of Measure: score on a scale
ISMO 2.1  (2.64)
Patch 3.1  (2.98)
Ointment 1.5  (2.12)
0.3 Sublingual 0.36  (1.18)
0.6 Sublingual 0.6  (1.62)
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)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title ISMO - Treatment Arm 1 Patch (Nitro-Dur) - Treatment Arm 2 Ointment (Nitrol) - Treatment Arm 3 0.3 Sublingual (Nitrostat 1) - Treatment Arm 4 0.6 Sublingual (Nitrostat 2) - Treatment Arm 5 Placebo Ointment- Treatment Arm 6
Hide Arm/Group Description

Isosorbide Mononitrate 20mg Oral Tablet

Nitrates (NABT Main trial)

Nitroglycerin Extended Release Patch 160mg

Nitrates (NABT Main trial)

Nitroglycerin Ointment 2% USP

Nitrates (NABT Main trial)

Nitroglycerin 0.3mg Sublingual Tablet

Nitrates (NABT Main trial)

Nitroglycerin 0.6mg Sublingual Tablet

Nitrates (NABT Main trial)

Placebo Ointment

Placebo: Placebo ointment Nitrates (NABT Main trial)

All-Cause Mortality
ISMO - Treatment Arm 1 Patch (Nitro-Dur) - Treatment Arm 2 Ointment (Nitrol) - Treatment Arm 3 0.3 Sublingual (Nitrostat 1) - Treatment Arm 4 0.6 Sublingual (Nitrostat 2) - Treatment Arm 5 Placebo Ointment- Treatment Arm 6
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
ISMO - Treatment Arm 1 Patch (Nitro-Dur) - Treatment Arm 2 Ointment (Nitrol) - Treatment Arm 3 0.3 Sublingual (Nitrostat 1) - Treatment Arm 4 0.6 Sublingual (Nitrostat 2) - Treatment Arm 5 Placebo Ointment- Treatment Arm 6
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/39 (0.00%)      0/38 (0.00%)      0/38 (0.00%)      1/39 (2.56%)      1/38 (2.63%)      0/37 (0.00%)    
Nervous system disorders             
Transient Global Amnesia  0/39 (0.00%)  0 0/38 (0.00%)  0 0/38 (0.00%)  0 0/39 (0.00%)  0 1/38 (2.63%)  1 0/37 (0.00%)  0
Vascular disorders             
Stroke  0/39 (0.00%)  0 0/38 (0.00%)  0 0/38 (0.00%)  0 1/39 (2.56%)  1 0/38 (0.00%)  0 0/37 (0.00%)  0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
ISMO - Treatment Arm 1 Patch (Nitro-Dur) - Treatment Arm 2 Ointment (Nitrol) - Treatment Arm 3 0.3 Sublingual (Nitrostat 1) - Treatment Arm 4 0.6 Sublingual (Nitrostat 2) - Treatment Arm 5 Placebo Ointment- Treatment Arm 6
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   17/39 (43.59%)      21/38 (55.26%)      17/38 (44.74%)      10/39 (25.64%)      12/38 (31.58%)      6/37 (16.22%)    
Gastrointestinal disorders             
Nausea  1/39 (2.56%)  1 2/38 (5.26%)  2 0/38 (0.00%)  0 2/39 (5.13%)  2 1/38 (2.63%)  1 0/37 (0.00%)  0
Nervous system disorders             
Headache  17/39 (43.59%)  17 21/38 (55.26%)  21 17/38 (44.74%)  17 10/39 (25.64%)  10 12/38 (31.58%)  112 6/37 (16.22%)  6
Dizziness  1/39 (2.56%)  1 2/38 (5.26%)  2 1/38 (2.63%)  1 0/39 (0.00%)  0 2/38 (5.26%)  2 0/37 (0.00%)  0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. Sophie Jamal
Organization: Womens' College Hospital
Phone: 416-351-3732 ext 2873
Responsible Party: Sophie Jamal, University of Toronto
ClinicalTrials.gov Identifier: NCT01387672     History of Changes
Other Study ID Numbers: 062011
First Submitted: June 30, 2011
First Posted: July 4, 2011
Results First Submitted: February 17, 2015
Results First Posted: May 8, 2015
Last Update Posted: May 8, 2015