OsteoporosisPhase 3NCT00252421
The Nitrate and Bone Study: Effects of Nitrates on Osteoporosis
A Phase 3 study testing Nitroglycerin ointment 15 mg/day daily for 24 month in people with Osteoporosis, run by University of Toronto at 1 site in Canada.
Trial summary
Osteoporosis or "thinning of the bones" affects in 1 in 4 Canadian women and 1 in 8 Canadian men. Moreover, while the rates of osteoporosis among Canadians are stabilizing, worldwide the number of people afflicted with osteoporosis continues to rise. 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?
- Nitroglycerin ointment 15 mg/day daily for 24 month
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 243 participants
- Where
- 1 siteCanada
- Study dates
- Oct 2005to Jul 2010
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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
- Women aged 50 and older
- Lumbar spine BMD (L1 to L4) T score between 0 and -2.0
- At least 3 years postmenopausal
Who cannot join
- Prior low trauma hip or vertebral fracture
- Total hip or femoral neck T score of <-2.0
- Bone disorders other than osteopenia (e.g., hyperparathyroidism or Paget's disease)
- Treatment within six months of study entry with androgen, calcitonin, estrogen, progesterone, fluoride in a tablet form, raloxifene, tamoxifen, etidronate, prednisone or an equivalent at 5 mg/d for 12 months or greater, lithium or anticonvulsants
- Alendronate or risedronate use for at least four weeks, within the last three years
- Current treatment with nitrates
Show all 13Show fewer
- Systolic blood pressure of =<100 mm Hg or diastolic blood pressure >=100 mm Hg at the baseline screening examination
- Abnormal electrocardiogram (ECG) at the baseline screening examination
- history of myocardial infarction, angina, valvular or congenital heart disease
- Disabling conditions that may interfere with follow-up visits
- Inability to give informed consent
- Migraine headaches
- Hypersensitivity to nitrates
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effects of Organic Nitrates on Osteoporosis: Part 2
Osteoporosis or "thinning of the bones" affects in 1 in 4 Canadian women and 1 in 8 Canadian men. Moreover, while the rates of osteoporosis among Canadians are stabilizing, worldwide the number of people afflicted with osteoporosis continues to rise. The most serious complication of osteoporosis is a broken bone or fracture. Fractures due to osteoporosis can result in long hospital stays, dependence on others, and premature death. While there are several medications that prevent osteoporosis they all have side effects. For example, postmenopausal women who take hormone replacement therapy (HRT) are at increased risk of breast cancer and heart disease. In addition, drugs to prevent osteoporosis are expensive and not available worldwide. Therefore, it is essential that researchers continue to identify and test new medications for the prevention of osteoporosis.
The purpose of the research is to determine if nitrates, a group of drugs that are widely available, inexpensive, and commonly used to treat chest pain or angina, can prevent osteoporosis in women. If the researchers find that nitrates prevent osteoporosis, a widely available, inexpensive treatment for osteoporosis prevention that does not have any long term side effects would have been identified. This will improve the health of patients with osteoporosis worldwide.
Read the detailed description
This proposal consists of two studies. The objective of the first study is to determine which of isosorbide mononitrate (ISMO) at 20 mg/day or nitroglycerin ointment (NTG) at 15 mg/day results in fewer headaches. The nitrate that is best tolerated will be used in a second study with one main objective: To determine if postmenopausal women with a T-score at the lumbar spine (L1 to L4) between 0 and -2.0 randomized to two years of treatment with intermittent nitrates have a greater increase in spine BMD as compared to women randomized to placebo.
We hypothesize that:
- Women will report fewer headaches when they are randomized to intermittent NTG ointment at 15 mg/day compared to intermittent oral ISMO at 20 mg/day.
- After two years, women randomized to intermittent nitrates will have a greater percent increase in lumbar spine BMD compared with women randomized to placebo.
To test these hypotheses we will execute 2 trials both of which include postmenopausal women, aged 50 and older, with BMD T scores at the lumbar spine between 0 and -2.0. We will exclude subjects with prior osteoporotic fractures or OP by BMD testing, subjects with current metabolic bone or cardiovascular disease, subjects taking treatments for OP, subjects with migraine headaches, and subjects with known hypersensitivity to nitrates. We will use computer generated randomization to allocate subjects to treatment assignments. To avoid bias the studies will be double-blind. The first study, which uses a crossover design, will recruit 22 subjects who will be randomly assigned to each of NTG ointment and ISMO for one week. In between treatments there will be a two week wash out period. Subjects will rate headaches on a daily basis using a visual analog scale and for each subject I will calculate the mean headache score over the 7 day treatment period for both treatments. We will then calculate the mean headache score (considering all subjects) for NTG and the mean headache score for ISMO. We will compare the mean headache scores for both treatments and the nitrate preparation that is best tolerated (lowest mean score) will be used in a second placebo controlled study (the main study) whose primary objective is to assess the effects of intermittent nitrates on spine BMD (L1 to L4) in 280 postmenopausal women. To limit differential drop out due to headaches among subjects randomized to nitrates, the main trial will follow a run-in phase during which all subjects will receive nitrates for one week. Only those subjects who do not have headaches resulting in discontinuation of the study medication during the nitrate run-in phase will enter the main study.
- Conditions
- Osteoporosis
- Being tested
- Nitroglycerin ointment 15 mg/day daily for 24 month, Placebo ointment daily for 24 month
- Keywords
- osteoporosis, bone mineral density, nitrates
- Medical subject headings
- Osteoporosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitroglycerin ointment 15 mg/day daily for 24 monthDrug
Nitroglycerin ointment 15 mg/day applied daily for 24 mth
Placebo ointment daily for 24 monthDrug
Placebo ointment applied daily for 24 mth
| Study group | Role | What they receive |
|---|---|---|
| Nitroglycerin | Active comparator | Nitroglycerin ointment 15 mg/day daily for 24 month Receives: Drug: Nitroglycerin ointment 15 mg/day daily for 24 month |
| Placebo | Placebo comparator | Placebo ointment daily for 24 month Receives: Drug: Placebo ointment daily for 24 month |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pilot Study: Mean headache score associated with each of intermittent nitroglycerin ointment (NTG) and isosorbide mononitrate (ISMO) use
Measured: 6 months
Main Study: Change from baseline in bone mineral density (BMD) at the lumbar spine over 24 months
Measured: 48 months
Secondary outcomes (1)
Change from baseline in total hip BMD; Change from baseline in bone formation and bone resorption markers; Adverse events and Bone microarchitecture: trabecular and cortical volumetric bone densities at the radius and tibia.
Measured: 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2005 (estimated)
- Study startOct 2005
- Primary completionJun 2010
- Study completionJul 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 243 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Responsible party
- Principal investigator, Sophie Jamal, University of Toronto
- Investigators
- Sophie A. Jamal, MD, PhD, Principal investigator, Women's College Hospital, St. Michael's Hospital, University of Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00252421
- Sponsor's protocol ID
- 05-169
- Other IDs
- ISRCTN 94484747
- Status last verified
- May 2014
- First submitted
- 10 Nov 2005
- Last updated
- 21 May 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Organic Nitrates on Osteoporosis: Part 2
- ClinicalTrials.gov ID
- NCT00252421
- Acronym / sponsor ID
- 05-169
- Conditions
- Osteoporosis
- Keywords
- osteoporosis, bone mineral density, nitrates
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 243 participants (actual)
- Lead sponsor
- University of TorontoUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Study start
- Oct 2005
- Primary completion
- Jun 2010 (actual)
- Study completion
- Jul 2010 (actual)
- First posted
- 11 Nov 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Osteoporosis or "thinning of the bones" affects in 1 in 4 Canadian women and 1 in 8 Canadian men. Moreover, while the rates of osteoporosis among Canadians are stabilizing, worldwide the number of people afflicted with osteoporosis continues to rise. The most serious complication of osteoporosis is a broken bone or fracture. Fractures due to osteoporosis can result in long hospital stays, dependence on others, and premature death. While there are several medications that prevent osteoporosis they all have side effects. For example, postmenopausal women who take hormone replacement therapy (HRT) are at increased risk of breast cancer and heart disease. In addition, drugs to prevent osteoporosis are expensive and not available worldwide. Therefore, it is essential that researchers continue to identify and test new medications for the prevention of osteoporosis.
The purpose of the research is to determine if nitrates, a group of drugs that are widely available, inexpensive, and commonly used to treat chest pain or angina, can prevent osteoporosis in women. If the researchers find that nitrates prevent osteoporosis, a widely available, inexpensive treatment for osteoporosis prevention that does not have any long term side effects would have been identified. This will improve the health of patients with osteoporosis worldwide.
Detailed description
This proposal consists of two studies. The objective of the first study is to determine which of isosorbide mononitrate (ISMO) at 20 mg/day or nitroglycerin ointment (NTG) at 15 mg/day results in fewer headaches. The nitrate that is best tolerated will be used in a second study with one main objective: To determine if postmenopausal women with a T-score at the lumbar spine (L1 to L4) between 0 and -2.0 randomized to two years of treatment with intermittent nitrates have a greater increase in spine BMD as compared to women randomized to placebo.
We hypothesize that:
- Women will report fewer headaches when they are randomized to intermittent NTG ointment at 15 mg/day compared to intermittent oral ISMO at 20 mg/day.
- After two years, women randomized to intermittent nitrates will have a greater percent increase in lumbar spine BMD compared with women randomized to placebo.
To test these hypotheses we will execute 2 trials both of which include postmenopausal women, aged 50 and older, with BMD T scores at the lumbar spine between 0 and -2.0. We will exclude subjects with prior osteoporotic fractures or OP by BMD testing, subjects with current metabolic bone or cardiovascular disease, subjects taking treatments for OP, subjects with migraine headaches, and subjects with known hypersensitivity to nitrates. We will use computer generated randomization to allocate subjects to treatment assignments. To avoid bias the studies will be double-blind. The first study, which uses a crossover design, will recruit 22 subjects who will be randomly assigned to each of NTG ointment and ISMO for one week. In between treatments there will be a two week wash out period. Subjects will rate headaches on a daily basis using a visual analog scale and for each subject I will calculate the mean headache score over the 7 day treatment period for both treatments. We will then calculate the mean headache score (considering all subjects) for NTG and the mean headache score for ISMO. We will compare the mean headache scores for both treatments and the nitrate preparation that is best tolerated (lowest mean score) will be used in a second placebo controlled study (the main study) whose primary objective is to assess the effects of intermittent nitrates on spine BMD (L1 to L4) in 280 postmenopausal women. To limit differential drop out due to headaches among subjects randomized to nitrates, the main trial will follow a run-in phase during which all subjects will receive nitrates for one week. Only those subjects who do not have headaches resulting in discontinuation of the study medication during the nitrate run-in phase will enter the main study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nitroglycerin | Active comparator | Drug: Nitroglycerin ointment 15 mg/day daily for 24 monthNitroglycerin ointment 15 mg/day daily for 24 month |
| Placebo | Placebo comparator | Drug: Placebo ointment daily for 24 monthPlacebo ointment daily for 24 month |
Who may qualify
- Ages
- 50 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Women aged 50 and older
- Lumbar spine BMD (L1 to L4) T score between 0 and -2.0
- At least 3 years postmenopausal
Key exclusion criteria (13 listed)
- Prior low trauma hip or vertebral fracture
- Total hip or femoral neck T score of <-2.0
- Bone disorders other than osteopenia (e.g., hyperparathyroidism or Paget's disease)
- Treatment within six months of study entry with androgen, calcitonin, estrogen, progesterone, fluoride in a tablet form, raloxifene, tamoxifen, etidronate, prednisone or an equivalent at 5 mg/d for 12 months or greater, lithium or anticonvulsants
- Alendronate or risedronate use for at least four weeks, within the last three years
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 |
|---|---|---|
| Nitroglycerin ointment 15 mg/day daily for 24 monthNitroglycerin ointment 15 mg/day applied daily for 24 mth | Drug | Nitroglycerin |
| Placebo ointment daily for 24 monthPlacebo ointment applied daily for 24 mth | Drug | Placebo |
Primary outcome
Pilot Study: Mean headache score associated with each of intermittent nitroglycerin ointment (NTG) and isosorbide mononitrate (ISMO) use
Time frame: 6 months
Main Study: Change from baseline in bone mineral density (BMD) at the lumbar spine over 24 months
Time frame: 48 months
1 secondary outcome
Change from baseline in total hip BMD; Change from baseline in bone formation and bone resorption markers; Adverse events and Bone microarchitecture: trabecular and cortical volumetric bone densities at the radius and tibia.
Time frame: 48 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2014.
- 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.
Related trials for Osteoporosis
RecruitingObservational study
A Clinical Study to Collect Real-wordt Data on Safety and Clinical Performance of the VCFix Spinal System for Treatment of Vertebral Compression Fractures of (Suspected) Osteoporotic Origin.
Vertebra Compression Fracture
Active, not recruitingObservational study
The Impact of Osteosarcopenia on Falls, Kinesiophobia, and Quality of Life in Postmenopausal Women
Osteosarcopenia, Sarcopenia
Active, not recruitingPhase 2
TCM Formula vs. HMB in Pre-Frail Elders: Muscle Strength and Bone Status
Pre-Frailty, Sarcopenia
Not yet recruitingPhase 4
Romosozumab and Denosumab Combination Therapy for Osteoporosis
Postmenopausal Osteoporosis
RecruitingObservational study
Assessment and Comparison of Osteoporosis Risk Factors After Stroke
Stroke, Osteoporosis
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 principal investigator
Women's College Hospital, St. Michael's Hospital, University of Toronto
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 Nitroglycerin ointment 15 mg/day daily for 24 month 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 3 inclusion and 13 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 21 May 2014. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Pilot Study: Mean headache score associated with each of intermittent nitroglycerin ointment (NTG) and isosorbide mononitrate (ISMO) use (time frame: 6 months). The study lists 2 primary outcomes in all. 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 NCT00252421, which also lists 1 linked publication.
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 21 May 2014.