Preventing Osteoporosis Using Denosumab

Osteoporosis Clinical Trial

— PROUD  

Official title:

Sustaining Skeletal Health in Frail Elderly

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02753283
• Other study ID #: STUDY19050268
• Secondary ID: 1R01AG052123-01
• Status: Completed
• Phase: Phase 4
• Start date: June 2016
• Est. completion date: August 2023

Study information

• Verified date: October 2023
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 201
• Est. completion date: August 2023
• Est. primary completion date: August 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Osteoporosis
• Osteoporosis, Postmenopausal
• Osteoporotic Fractures

Intervention

Drug:
• denosumab
Semi-annual dose: 60 mg injection; Vitamin D 800-1000 IU/daily and Calcium approximately 1200 mg/daily (dietary + supplement)
• 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

Locations

Country	Name	City	State
United States	UPMC Senior Communities	Pittsburgh	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Susan L. Greenspan	National Institute on Aging (NIA), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bone density of the total hip	Bone Mineral Density (BMD) of the total hip at 24 months as assessed by dual-energy x-ray absorptiometry (DXA)	24 months
Primary	Bone density of the spine	Bone Mineral Density (BMD) of the spine at 24 months as assessed by dual-energy x-ray absorptiometry (DXA)	24 months
Primary	Extension - Zoledronic Acid Infusion Safety Treatment: Bone density of the total hip	Bone Mineral Density (BMD) of the total hip at 33 months as assessed by dual-energy x-ray absorptiometry (DXA)	33 months
Primary	Extension - Zoledronic Acid Infusion Safety Treatment: Bone density of the total hip	Bone Mineral Density (BMD) of the total hip at 39 months as assessed by dual-energy x-ray absorptiometry (DXA)	39 months
Primary	Extension - Zoledronic Acid Infusion Safety Treatment: Bone density of the spine	Bone Mineral Density (BMD) of the spine at 33 months as assessed by dual-energy x-ray absorptiometry (DXA)	33 months
Primary	Extension - Zoledronic Acid Infusion Safety Treatment: Bone density of the spine	Bone Mineral Density (BMD) of the spine at 39 months as assessed by dual-energy x-ray absorptiometry (DXA)	39 months