Clinical trial NCT04167163: Abaloparatide Before Total Knee Arthroplasty
Official title: An Open-Label Phase 2 Study of Abaloparatide to Mitigate Distal Femoral Bone Loss Following Total Knee Arthroplasty
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Osteoporosis
Arthroplasties, Knee Replacement
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: Radius Health, Inc.
First posted: 2019-11-18
Enrollment: 58
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The investigator hypothesizes that treating osteoporotic patients with abaloparatide prior to and after total knee arthroplasty will significantly reduce the amount of bone loss.

Detailed description: In primary unilateral total knee arthroplasty patients, The investigator will examine the effect of daily abaloparatide therapy in clinical osteoporotic patients beginning 3 months pre-op and continued for a total of 15 months. This will be compared to osteopenic patients receiving no therapy as well as previously published values in untreated osteoporotic patients 12 months following Total Knee Arthroplasty (TKA).

Eligibility criteria: Inclusion Criteria

1. Post-menopausal women and men age ge ≥ 55 years and scheduled to undergo primary TKA at the University of Wisconsin Total Joint Program.
2. Osteoporosis, i.e., BMD T-score (using female reference data) ≤ -2.5 at the lumbar spine, femoral neck OR total hip or ≤ -1.1 with Vertebral Fracture Assessment confirmed vertebral fracture or history of low-trauma nonvertebral fracture in the past 5 years OR osteopenia, BMD T-score (using female reference data) -1.1 to -2.4 at the lumbar spine, femoral neck or total hip and no prior low-trauma fracture.
3. Serum calcium (albumin-corrected), serum creatinine and Parathyroid(PTH) values all within the normal range and 25(OH)D \> 10 ng/mL.
4. Willing to supplement with daily calcium and/or vitamin D3 at protocol specified doses.
5. Able to provide written informed consent.

Exclusion Criteria

1. Unevaluable distal femur BMD due to hardware or other artifacts.
2. History of bone disorders (e.g., Paget's disease) other than osteoporosis.
3. History of prior external beam or implant radiation therapy involving the skeleton other than radioiodine.
4. History of chronic or recurrent renal, hepatic, pulmonary, allergic, cardiovascular, gastrointestinal, endocrine, central nervous system, hematologic or metabolic diseases, or immunologic, emotional and/or psychiatric disturbances that, in opinion of the principal investigator, would compromise study data validity.
5. History of Cushing's disease, growth hormone deficiency or excess, hyperthyroidism, hypo- or hyperparathyroidism or malabsorptive syndromes within the past year.
6. History of significantly impaired renal function (serum creatinine \>2.0 mg/dL. If the serum creatinine is \> 1.5 and ≤ 2.0 mg/dL, the calculated creatinine clearance (Cockcroft-Gault) must be ≥ 37 mL/min.
7. History of nephrolithiasis or urolithiasis within the past five years.
8. History of cancer in prior 5 years (basal cell or squamous skin cancer is permissible).
9. History of osteosarcoma at any time.
10. Patients known to be positive for Hepatitis B, Hepatitis C, HIV-1 or HIV-2.
11. Known hypersensitivity to any of the test materials or related compounds.
12. Prior treatment with PTH- or PTHrP-derived drugs, (ABL, teriparatide or PTH (1-84)).
13. Prior treatment with intravenous bisphosphonates at any time or oral bisphosphonates within the past three years. Patients who had received a short course of oral bisphosphonate therapy (3 months or less) may be enrolled as long as the treatment occurred 6 or more months prior to enrollment.
14. Treatment with fluoride or strontium in the past five years or prior treatment with bone-acting investigational agents at any time.
15. Treatment with calcitonin the past 6 months or denosumab in the past 18 months.
16. Treatment with anticonvulsants affecting vitamin D metabolism (phenobarbital, phenytoin, carbamazepine or primidone) or chronic heparin within the prior 6 months.
17. Treatment with anabolic steroids or calcineurin inhibitors (cyclosporin, tacrolimus)
18. Daily treatment with oral, intranasal or inhaled glucocorticoids in the prior 12 months.
19. Exposure to any investigational drug within 12 months.
20. Consumption of \> 2 alcoholic drinks per day or use of illegal drugs within 12 months of screening.
21. Not suitable for study participation due to other reasons at the investigators discretion.

Primary outcomes:
measure: Change in Distal femoral Bone mineral density (BMD) at the 25% regions of interest (ROIs)
timeFrame: Baseline and 18 months
Secondary outcomes:
measure: Change in Distal femoral BMD at the 15% and 60 %ROI
timeFrame: Baseline and 18 months
measure: Change in Femur cortical thickness at the 15%, 25% and 60% femur ROIs
timeFrame: Baseline and 18 months
measure: TBS assessment by TRIP at the 15%, 25% and 60% femur ROIs
timeFrame: 18 months
measure: Knee injury & Osteoarthritis Outcome Score (KOOS) JR
timeFrame: 18 months
measure: Change in Veterans RAND 12 (VR-12) Question Health Survey score
timeFrame: Baseline and 18 months
measure: Forgotten Joint Survey(FJS) score
timeFrame: 18 months
measure: Change in body composition using bioelectrical impedance analysis of lean mass
timeFrame: Baseline and 18 months
measure: Change in body composition using bioelectrical impedance analysis of skeletal mass.
timeFrame: Baseline and 18 months
measure: Change in body composition using bioelectrical impedance analysis of fat mass.
timeFrame: Baseline and 18 months
measure: TKA complications: Number of participants needed revision surgery
timeFrame: 18 months
measure: TKA complications: Number of participants had fracture
timeFrame: 18 months
measure: Precision Error on Knee Bone Density Measurement
timeFrame: up to 15 months
Other outcomes:
Locations:
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Neil Binkley, MD
role: PRINCIPAL_INVESTIGATOR
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