PROUD: Preventing Osteoporosis Using Denosumab
Study Details
Study Description
Brief Summary
The purpose of this research study is to find out if denosumab (Prolia®), an injection given in the arm under the skin every 6 months, works to treat bone loss and prevent it from worsening in older men and women (ages 65 and older) who have osteoporosis and reside in long-term care (LTC) facilities.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 4 |
Detailed Description
Objective:
The long term goal is to improve health, well-being and quality of life in the frail long-term care (LTC) elderly population by reducing fractures. The short term goal is to demonstrate efficacy of the non-bisphosphonate denosumab to improve bone mineral density (BMD), a necessary (but not sufficient) pre-condition of a large fracture reduction trial. The investigators propose to conduct a 2-year, randomized, double-blind, calcium-vitamin D controlled trial to test the efficacy and predictability of the antiresorptive RANK ligand inhibitor, denosumab (60 mg), among a cohort of 212 institutionalized, under-served, frail men and women ≥65 years old in LTC.
Specific Aims:
Aim 1: To evaluate efficacy of denosumab in improving/maintaining bone mineral density. The investigators will measure conventional hip and spine bone mineral density (BMD).
Primary Hypothesis: After 2 years, women and men on denosumab will have greater hip and spine BMD increases.
Zoledronic Acid Infusion Safety Treatment and Follow-up Extension:
After the trial was started, case reports suggested a potential increase in fracture risk with disuse. A post hoc analysis that combined the pivotal denosumab trial and extension trial data suggested there was an increase in multiple vertebral fractures when patients discontinued therapy. Following discontinuation of denosumab/placebo, all patients will be offered treatment with 1 dose of intravenous zoledronic acid 5 mg. For those consenting to receive end of study treatment, the zoledronic acid will be given at month 27 for an individual patient.
Zoledronic Acid Safety Infusion Extension Specific Aims:
Aim 1: To evaluate maintenance of bone mineral density (BMD). Zoledronic acid will be administered intravenously at 9 months post-denosumab (month 27) and assess BMD by DXA at months 33 and 39 (6 months and 12 months after zoledronic acid infusion).
Primary Hypothesis: Zoledronic acid will prevent BMD loss at the spine and hip following denosumab discontinuation.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Denosumab, then Zoledronic Acid Semi-annual dose: denosumab 60 mg semi-annual injection; Vitamin D 800-1000 IU/daily and Calcium approximately 1200 mg/daily (dietary + supplements); Zoledronic acid will be offered to all study participants upon completing the course of Denosumab. |
Drug: denosumab
Semi-annual dose: 60 mg injection; Vitamin D 800-1000 IU/daily and Calcium approximately 1200 mg/daily (dietary + supplement)
Other Names:
Dietary Supplement: Calcium and Vitamin D
Dietary supplement: Vitamin D 800-1000 IU/daily and Calcium approximately 1200 mg/daily (dietary + supplement)
Drug: Zoledronic Acid
One time safety treatment dose: 5 mg infusion
Other Names:
|
Placebo Comparator: Placebo Group, then Zoledronic Acid Semi-annual: placebo saline injection; Vitamin D 800-1000 IU/daily and Calcium approximately1200 mg/daily (dietary + supplements); Zoledronic acid will be offered to all study participants upon completing the course of placebo. |
Drug: Placebo
Semi-annual saline injection
Dietary Supplement: Calcium and Vitamin D
Dietary supplement: Vitamin D 800-1000 IU/daily and Calcium approximately 1200 mg/daily (dietary + supplement)
Drug: Zoledronic Acid
One time safety treatment dose: 5 mg infusion
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Bone density of the total hip [24 months]
Bone Mineral Density (BMD) of the total hip at 24 months as assessed by dual-energy x-ray absorptiometry (DXA)
- Bone density of the spine [24 months]
Bone Mineral Density (BMD) of the spine at 24 months as assessed by dual-energy x-ray absorptiometry (DXA)
- Extension - Zoledronic Acid Infusion Safety Treatment: Bone density of the total hip [33 months]
Bone Mineral Density (BMD) of the total hip at 33 months as assessed by dual-energy x-ray absorptiometry (DXA)
- Extension - Zoledronic Acid Infusion Safety Treatment: Bone density of the total hip [39 months]
Bone Mineral Density (BMD) of the total hip at 39 months as assessed by dual-energy x-ray absorptiometry (DXA)
- Extension - Zoledronic Acid Infusion Safety Treatment: Bone density of the spine [33 months]
Bone Mineral Density (BMD) of the spine at 33 months as assessed by dual-energy x-ray absorptiometry (DXA)
- Extension - Zoledronic Acid Infusion Safety Treatment: Bone density of the spine [39 months]
Bone Mineral Density (BMD) of the spine at 39 months as assessed by dual-energy x-ray absorptiometry (DXA)
Eligibility Criteria
Criteria
Inclusion Criteria:
Ambulatory male and female residents with osteoporosis or low bone mass (at risk for fracture) ages 65 and older will be considered if:
-
Reside in long-term care institution (nursing home or assisted living facility); and
-
HaveOsteoporosis: (1) by bone density [spine, hip or forearm Bone Mineral Density (BMD) T-score ≤ -2.5]; (2) A previous adult fragility fracture of the spine or hip; or (3) Would be treated based on FRAX® and the National Osteoporosis Foundation (NOF) treatment thresholds of a 10 year risk of ≥ 20% for a major fracture or ≥ 3% for hip fracture suing femoral neck BMD.
Exclusion Criteria:
-
Institutionalized residents with subacute illnesses who are not expected to survive or who will be discharged in < 2 years.
-
Non-ambulatory residents (those who cannot stand and pivot with assistance in order to transfer to the DXA table).
-
Those currently on therapy (including bisphosphonate, denosumab, or teriparatide) or who have been on a bisphosphonate for > 1year during the previous 2 years because some bisphosphonates are long acting.
-
Those with a history of hypocalcemia or contraindication for treatment. We will screen for these conditions by detailed history, chart review, and baseline laboratory analyses.
-
Those with vitamin D levels < 25ng/mL will be treated with vitamin D 50,000 IU/wk for 8 weeks; they will be enrolled if the follow-up vitamin D level is 25 ng/mL or more (if after 2 rounds of vitamin D repletion their vitamin D level is not at least 25 ng/mL, they will not be eligible to be randomized into the study).
-
Those on dialysis or with stage 5 chronic kidney disease (eGFR<15ml/min) will be excluded at screening.
-
Those requiring tooth extraction or oral surgery will not be enrolled until cleared by a dentist.
-
Patients will be allowed to continue on glucocorticoids and anticonvulsants because their use is common in this population.
-
Those on glucocorticoids and anticonvulsants will be allowed to continue in the study because their use is common in this population.
-
Those on hormone replacement therapy (HRT), raloxifene, or prescribed protective hip pads by their Primary Care Physician (PCP) will be allowed to participate and continue on these therapies.
-
We will suggest that participants stop long-term calcitonin as it has been discontinued in Europe due to cancer concerns.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | UPMC Senior Communities | Pittsburgh | Pennsylvania | United States | 15213 |
Sponsors and Collaborators
- Susan L. Greenspan
- National Institutes of Health (NIH)
- National Institute on Aging (NIA)
Investigators
- Principal Investigator: Susan L Greenspan, MD, University of Pittsburgh
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- STUDY19050268
- 1R01AG052123-01