RUBI: Romosozumab Use to Build Skeletal Integrity

Study Details

Study Description

Brief Summary

The purpose of this study is to find out if one year of romosozumab (Evenity®), a monthly injection given in the arm under the skin, prior to an infusion of zoledronic acid Reclast®, works to treat bone loss and prevent it from worsening in older women (ages 65 and older) who have osteoporosis and reside in long-term care (LTC) facilities.

Condition or Disease	Intervention/Treatment	Phase
Osteoporosis Osteoporosis, Postmenopausal Osteoporosis Fracture	Drug: Romosozumab Drug: Placebo Drug: Zoledronic acid Dietary Supplement: Calcium and Vitamin D	Phase 4

Detailed Description

Objective:

The long-term goal of this study is to improve health, well-being and quality of life in the frail Long-term Care (LTC) population by reducing fractures. The short-term goal is to demonstrate efficacy of the novel dual action Romosozumab (ROMO) to improve Bone Mineral Density (BMD) and skeletal integrity and its safety, a necessary (but not sufficient) precondition 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 safety of the sclerostin inhibitor ROMO among a cohort of 200 underserved, institutionalized, frail women ≥65 years old. Bone measures will be collected in a mobile lab. The monthly subcutaneous therapy negates concerns regarding poor oral absorption or compliance. The use of annual Zoledronic Acid (ZOL) to follow ROMO, will prevent bone loss and insure the entire group will be provided with at least 1 year of therapy. The groups include: 1) ROMO →ZOL vs 2) placebo →ZOL.

Aim 1: Evaluate efficacy of bone building ROMO treatment prior to ZOL in improving bone mineral density. H1: Women on ROMO →ZOL will have greater hip and spine BMD increases after 2 years (H1.1-primary) and 1 year (H1.2), and at other locations (H1.3).

Aim 2: Examine improvements in 3D trabecular microstructure (TBS), markers of bone turnover and collect preliminary evidence for a fracture reduction trial. The investigators will measure vertebral trabecular bone score (TBS), a 3-D microarchitectural image and parameters of the spine, hip, and lateral spine H2: Women on ROMO →ZOL will have greater increases in TBS measures of spine, hip and lateral spine after one (H2.1) and two (H2.2) years; and improvement in bone turnover markers (CTx and P1NP; H2.3).

Aim 3: Determine characteristics associated with responders and non responders. The investigators will use multiple regression analyses and other data mining techniques to identify baseline characteristics of responders and non-responders. H3.1: Poor baseline functional/cognitive status/immobility will be associated with poor bone healthy outcomes. H3.2: Greater early changes in bone turnover markers will be associated with greater skeletal improvements.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

Innovative Approach to Geriatric Osteoporosis

Actual Study Start Date :

Sep 15, 2021

Anticipated Primary Completion Date :

Sep 1, 2027

Anticipated Study Completion Date :

Sep 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Romosozumab, then Zoledronic Acid Monthly dose: 210 mg Romosozumab subcutaneous injections; Vitamin D 800-1000 IU/daily and Calcium approximately 1200 mg/daily (dietary + supplements); all participants will receive 5 mg Zoledronic Acid IV infusion at the Month 12 visit.	Drug: Romosozumab Monthly dose: 210 mg subcutaneous injection Other Names: Evenity Drug: Zoledronic acid 5 mg IV infusion at Month 12 Visit Other Names: Reclast Dietary Supplement: Calcium and Vitamin D Vitamin D 800-1000 IU/daily and Calcium approximately 1200 mg/daily (dietary + supplement)
Placebo Comparator: Placebo, then Zoledronic Acid Monthly dose: placebo saline subcutaneous injections; Vitamin D 800-1000 IU/daily and Calcium approximately 1200 mg/daily (dietary + supplements); all participants will receive 5 mg Zoledronic Acid IV infusion at the Month 12 visit.	Drug: Placebo Monthly saline injection Drug: Zoledronic acid 5 mg IV infusion at Month 12 Visit Other Names: Reclast Dietary Supplement: Calcium and Vitamin D Vitamin D 800-1000 IU/daily and Calcium approximately 1200 mg/daily (dietary + supplement)

Arm

Intervention/Treatment

Experimental: Romosozumab, then Zoledronic Acid

Monthly dose: 210 mg Romosozumab subcutaneous injections; Vitamin D 800-1000 IU/daily and Calcium approximately 1200 mg/daily (dietary + supplements); all participants will receive 5 mg Zoledronic Acid IV infusion at the Month 12 visit.

Drug: Romosozumab

Monthly dose: 210 mg subcutaneous injection

Other Names:

Evenity

Drug: Zoledronic acid

5 mg IV infusion at Month 12 Visit

Other Names:

Reclast

Dietary Supplement: Calcium and Vitamin D

Vitamin D 800-1000 IU/daily and Calcium approximately 1200 mg/daily (dietary + supplement)

Placebo Comparator: Placebo, then Zoledronic Acid

Monthly dose: placebo saline subcutaneous injections; Vitamin D 800-1000 IU/daily and Calcium approximately 1200 mg/daily (dietary + supplements); all participants will receive 5 mg Zoledronic Acid IV infusion at the Month 12 visit.

Drug: Placebo

Monthly saline injection

Drug: Zoledronic acid

5 mg IV infusion at Month 12 Visit

Other Names:

Reclast

Dietary Supplement: Calcium and Vitamin D

Vitamin D 800-1000 IU/daily and Calcium approximately 1200 mg/daily (dietary + supplement)

Outcome Measures

Primary Outcome Measures

Bone Mineral 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 Mineral 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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

65 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Elderly women 65 years and older will be considered if:

They reside in an institution (nursing home or assisted living facility or senior care community);
They have a) osteoporosis by axial bone density (spine, hip or forearm BMD T-score≤ -2.5 SD), b) a previous adult fragility fracture of the spine or hip or c) would be treated based on FRAX and the National Osteoporosis Foundation (NOF) treatment thresholds of a 10 year risk of 10% for a major osteoporotic fracture or ≥ 3% for hip fracture using femoral neck BMD.
Willing and able to complete the informed consent process or provide consent by proxy.

Exclusion Criteria:

Those with subacute illnesses who are not expected to survive or who will be discharged in less than 2 years.
Those who have previously had an acute cardiovascular or cerebrovascular event within the preceding year. specifically, no recent history of coronary heart disease, heart failure, significant arrhythmia, stroke or Transient Ischemic Attack (TIA).
Recent cardiovascular disease (CVD) symptoms (significant chest pain, congestive heart failure, shortness of breath, or palpitations or cerebrovascular symptoms such as numbness or weakness in the face, arm, legs, difficulty talking, changes in vision, loss of balance, headache, feeling light-headed or dizzy).
Unstable angina.
Those who are currently on therapy (including a bisphosphonate, denosumab, teriparatide, abaloparatide or romosozumab) or have been on a bisphosphonate for greater than 1 year during the previous 2 years.
Those who are unable to take an intravenous bisphosphonate (zoledronic acid) due to renal insufficiency with eGFR < 35 ml/min.
Vitamin D levels <25 ng/mL.
Participants will be allowed to continue on medications known to affect bone and mineral metabolism (e.g., glucocorticoids, anticonvulsants) because their use is common in this population.
Those who have been treated in the past or present with osteoporosis agents, such as estrogen/progesterone or raloxifene will be allowed to participate and continue on these therapies if prescribed by their physician.
Patients will be allowed to wear hip pads if prescribed by their physician.
Non-ambulatory residents (those who cannot stand and pivot with assistance in order to transfer to the DXA table) will be excluded.