OsteoporosisPhase 4NCT02357277
The Effects of Inhaled Glucocorticoids on the Postmenopausal Skeleton
A Phase 4 study testing Budesonide in people with Osteoporosis, run by Columbia University.
Trial summary
There are over 10 million individuals with asthma using inhaled glucocorticoids (IGCs) in the United States. While oral GCs are recognized to have destructive skeletal effects, far less is known about the effects of IGCs. Read more about this study
- Who is it for?
- Ages 60 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Osteoporosis
- What is being tested?
- Budesonide
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Mar 2015to Nov 2018
- Phase
- Phase 4
- 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 60 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age ≥ 60 years or at least > 5 years postmenopause (defined as 1 year without a menstrual period)
- No asthma and no history of GC use, either oral or inhaled
Who cannot join
- Use of oral GCs for > 4 weeks per year in the past 3 years
- History of smoking, to rule out overlapping chronic obstructive pulmonary disease (COPD)
- Other metabolic bone diseases (e.g. hyperparathyroidism, Paget's disease, osteogenesis imperfecta)
- Gastrointestinal Disease (malabsorption, celiac disease, inflammatory bowel disease)
- Endocrinopathies (i.e. untreated thyroid disease, Cushing's syndrome, prolactinoma,)
- Current use of osteoporosis medication (hormone replacement therapy (HRT), raloxifene, bisphosphonates, denosumab)
Show all 11Show fewer
- Current or past use of teriparatide
- estimated glomerular filtration rate (eGFR)< 45 ml/min calculated by MDRD112 to accommodate mild declines in renal function due to aging
- History of malignancy, except for cured skin cancers
- Diabetes, (HbA1c>6) as this disease is also associated with decreased bone formation
- Osteoporosis by Dual-energy X-ray Absorptiometry (DXA) at any site or an asymptomatic vertebral fracture
About this study
There are over 10 million individuals with asthma using inhaled glucocorticoids (IGCs) in the United States. While oral GCs are recognized to have destructive skeletal effects, far less is known about the effects of IGCs. This gap in our knowledge is of critical importance, not only because of the prevalence, chronic nature and long duration of IGC use, but also because several studies have found that patients using IGCs are at increased risk of fracture. Fracture risk is greatest in postmenopausal (PM) women, in whom IGCs may augment negative effects of estrogen loss and aging.
The investigators hypothesize that initiation of IGCs in IGC naïve PM women will lead to decreased bone formation and uncoupling of bone turnover, a potential mechanism for the effect of IGCs on the skeleton.
To test our hypothesis, the investigators will perform a randomized, controlled 4 week study of the acute effects of commonly used doses of budesonide (360 or 720 mcg) on bone turnover and circulating osteoblast precursors in 60 treatment naïve, non-asthmatic, PM women. These studies are of high clinical significance because there are currently no guidelines regarding screening, prevention or treatment for osteoporosis in patients using IGCs, nor is IGC use taken into account when calculating fracture risk in PM women, the group at highest risk of fracture. High quality evidence for low volumetric bone mineral density (BMD) and abnormal bone quality in PM women using IGCs has the potential to change clinical practice by supporting specific interventions to prevent bone loss and fractures.
Read the detailed description
The investigators will study acute biochemical and hormonal responses over 4 weeks to commonly prescribed moderate and high doses of budesonide one of the most widely prescribed IGCs, and the preferred drug for Medicare and Medicaid. Sixty treatment naïve PM non-asthmatic women will be randomized to one of 3 groups (20/group): placebo, budesonide 360 or 720 mcg/day. IGCs will be self-administered as 2 puffs twice daily. Budesonide will be provided as Pulmicort flexhaler. At the baseline visit, subjects will be taught proper technique for self-administration of the inhaled medications, including mouth rinsing after each dose. Since dry powder formulations will be used, spacer devices are not required. Women will be assessed at baseline, 1,2, and 4 weeks. This time period and schedule was chosen to ensure adequate time for IGCs to reach peak levels, and to assess the bone metabolic response. Given the 4-6 hr half-life of budesonide, steady state pharmacokinetics will be reached at one week. The investigators will monitor medication adherence using the inhaler's device counter. Visits will be conducted in the Metabolic Bone Diseases Unit. To measure systemic absorption, serum steroid levels will be directly measured.To assess the effects of IGC and dose on the hypothalamic-pituitary-adrenal (HPA) axis, morning (AM) cortisol will be measured at each visit and urinary free cortisol at baseline and 4 weeks.
- Conditions
- Osteoporosis
- Being tested
- Budesonide, Placebo Inhaler
- Keywords
- Osteoporosis, Glucocorticoids, Postmenopausal
- Medical subject headings
- Osteoporosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BudesonideDrug
Also called Pulmicort flexhaler
inhaled glucocorticoid budesonide as dry powder inhaler
Placebo InhalerOther
inhaled placebo
| Study group | Role | What they receive |
|---|---|---|
| Budesonide 360 mcg | Experimental | Budesonide dry powder inhaler 2 puffs of 90 mcg twice daily for 4 weeks Receives: Drug: Budesonide |
| Budesonide 720 mcg | Experimental | Budesonide dry powder inhaler 2 puffs of 180 mcg twice daily for 4 weeks Receives: Drug: Budesonide |
| Placebo | Placebo comparator | Placebo inhaler 2 puffs twice daily for 4 weeks Receives: Other: Placebo Inhaler |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Osteocalcin
The primary outcome will be the within-group change in serum osteocalcin from baseline to 4-weeks based on intention-to-treat analyses.
Measured: Baseline and 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2015 (estimated)
- Study startMar 2015
- Primary completionNov 2017 (estimated)
- Study completionNov 2018 (estimated)
Why it stopped: Lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for OsteoporosisStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe 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 4
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Emily M Stein, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02357277
- Sponsor's protocol ID
- AAAO5309
- Status last verified
- Jul 2017
- First submitted
- 3 Feb 2015
- Last updated
- 18 Jul 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Inhaled Glucocorticoids on the Postmenopausal Skeleton
- ClinicalTrials.gov ID
- NCT02357277
- Acronym / sponsor ID
- AAAO5309
- Conditions
- Osteoporosis
- Keywords
- Osteoporosis, Glucocorticoids, Postmenopausal
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Study start
- Mar 2015
- Primary completion
- Nov 2017 (estimated)
- Study completion
- Nov 2018 (estimated)
- First posted
- 6 Feb 2015 (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.
There are over 10 million individuals with asthma using inhaled glucocorticoids (IGCs) in the United States. While oral GCs are recognized to have destructive skeletal effects, far less is known about the effects of IGCs. This gap in our knowledge is of critical importance, not only because of the prevalence, chronic nature and long duration of IGC use, but also because several studies have found that patients using IGCs are at increased risk of fracture. Fracture risk is greatest in postmenopausal (PM) women, in whom IGCs may augment negative effects of estrogen loss and aging.
The investigators hypothesize that initiation of IGCs in IGC naïve PM women will lead to decreased bone formation and uncoupling of bone turnover, a potential mechanism for the effect of IGCs on the skeleton.
To test our hypothesis, the investigators will perform a randomized, controlled 4 week study of the acute effects of commonly used doses of budesonide (360 or 720 mcg) on bone turnover and circulating osteoblast precursors in 60 treatment naïve, non-asthmatic, PM women. These studies are of high clinical significance because there are currently no guidelines regarding screening, prevention or treatment for osteoporosis in patients using IGCs, nor is IGC use taken into account when calculating fracture risk in PM women, the group at highest risk of fracture. High quality evidence for low volumetric bone mineral density (BMD) and abnormal bone quality in PM women using IGCs has the potential to change clinical practice by supporting specific interventions to prevent bone loss and fractures.
Detailed description
The investigators will study acute biochemical and hormonal responses over 4 weeks to commonly prescribed moderate and high doses of budesonide one of the most widely prescribed IGCs, and the preferred drug for Medicare and Medicaid. Sixty treatment naïve PM non-asthmatic women will be randomized to one of 3 groups (20/group): placebo, budesonide 360 or 720 mcg/day. IGCs will be self-administered as 2 puffs twice daily. Budesonide will be provided as Pulmicort flexhaler. At the baseline visit, subjects will be taught proper technique for self-administration of the inhaled medications, including mouth rinsing after each dose. Since dry powder formulations will be used, spacer devices are not required. Women will be assessed at baseline, 1,2, and 4 weeks. This time period and schedule was chosen to ensure adequate time for IGCs to reach peak levels, and to assess the bone metabolic response. Given the 4-6 hr half-life of budesonide, steady state pharmacokinetics will be reached at one week. The investigators will monitor medication adherence using the inhaler's device counter. Visits will be conducted in the Metabolic Bone Diseases Unit. To measure systemic absorption, serum steroid levels will be directly measured.To assess the effects of IGC and dose on the hypothalamic-pituitary-adrenal (HPA) axis, morning (AM) cortisol will be measured at each visit and urinary free cortisol at baseline and 4 weeks.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Budesonide 360 mcg | Experimental | Drug: BudesonideBudesonide dry powder inhaler 2 puffs of 90 mcg twice daily for 4 weeks |
| Budesonide 720 mcg | Experimental | Drug: BudesonideBudesonide dry powder inhaler 2 puffs of 180 mcg twice daily for 4 weeks |
| Placebo | Placebo comparator | Other: Placebo InhalerPlacebo inhaler 2 puffs twice daily for 4 weeks |
Who may qualify
- Ages
- 60 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Age ≥ 60 years or at least > 5 years postmenopause (defined as 1 year without a menstrual period)
- No asthma and no history of GC use, either oral or inhaled
Key exclusion criteria (11 listed)
- Use of oral GCs for > 4 weeks per year in the past 3 years
- History of smoking, to rule out overlapping chronic obstructive pulmonary disease (COPD)
- Other metabolic bone diseases (e.g. hyperparathyroidism, Paget's disease, osteogenesis imperfecta)
- Gastrointestinal Disease (malabsorption, celiac disease, inflammatory bowel disease)
- Endocrinopathies (i.e. untreated thyroid disease, Cushing's syndrome, prolactinoma,)
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 |
|---|---|---|
| BudesonideAlso: Pulmicort flexhalerinhaled glucocorticoid budesonide as dry powder inhaler | Drug | Budesonide 360 mcg, Budesonide 720 mcg |
| Placebo Inhalerinhaled placebo | Other | Placebo |
Primary outcome
Change in Osteocalcin
Time frame: Baseline and 4 weeks
The primary outcome will be the within-group change in serum osteocalcin from baseline to 4-weeks based on intention-to-treat analyses.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2017.
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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.
Emily M Stein, MD principal investigator
Columbia University
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Budesonide in people with Osteoporosis, run by Columbia University.
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 2 inclusion and 11 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: withdrawn, as of the sponsor's last update on 18 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 was withdrawn before enrolling participants, so there are no results.
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?
Change in Osteocalcin (time frame: Baseline and 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Jul 2017.