The Effects of Inhaled Glucocorticoids on the Postmenopausal Skeleton

NCT02357277 | Withdrawn Phase 4

• 1 other identifier: AAAO5309
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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. 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.

Conditions

Osteoporosis

Keywords

Osteoporosis; Glucocorticoids; Postmenopausal

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline and 4 weeks

Study Arms (3)

Budesonide 360 mcg

EXPERIMENTAL

Budesonide dry powder inhaler 2 puffs of 90 mcg twice daily for 4 weeks

Drug: Budesonide

Budesonide 720 mcg

EXPERIMENTAL

Budesonide dry powder inhaler 2 puffs of 180 mcg twice daily for 4 weeks

Drug: Budesonide

Placebo

PLACEBO COMPARATOR

Placebo inhaler 2 puffs twice daily for 4 weeks

Other: Placebo Inhaler

Interventions

Budesonide DRUG

inhaled glucocorticoid budesonide as dry powder inhaler

Also known as: Pulmicort flexhaler

Budesonide 360 mcg; Budesonide 720 mcg

Placebo Inhaler OTHER

inhaled placebo

Placebo

Eligibility Criteria

• Age: 60 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Columbia University: lead

MeSH Terms

Conditions

Osteoporosis

Interventions

Budesonide

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Emily M Stein, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2015
• First Posted: February 6, 2015
• Study Start: March 1, 2015
• Primary Completion: November 1, 2017
• Study Completion: November 1, 2018
• Last Updated: July 18, 2017

Record last verified: 2017-07