Longjohn Amgen Study - Effect of Denosumab...

• Status: Withdrawn
• Trial end date: 2019-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The overall objective of the proposed study is to quantify bone loss around non-cemented total hip replacement femoral and acetabular components using DEXA analysis in patients receiving Prolia (denosumab) in the first year of follow up after total hip joint replacement surgery, and to compare this to bone loss in control hip replacement patients receiving a placebo.

The primary outcome variable will be the difference in loss of bone mineral density between the experimental group taking denosumab and the placebo control group, calculated as a percentage, in Gruen Zone 7, the proximal medial calcar region of the femur, over a follow-up period of 12 post-operative months.

The secondary objectives will be to assess the following variables:

• Bone turnover differences between the experimental group taking denosumab and the placebo control group, utilizing serum C-terminal cross-linking telopeptides of type I collagen (CTX-I) (bone resorption) and N-terminal propeptides of type I procollagen (P1NP) (bone formation).

• Difference in loss of bone mineral density between the experimental group taking denosumab and the placebo control group, calculated as a percentage, in each of Gruen Zones 1 through 6, periprosthetic femur.

• Difference in loss of bone mineral density between the experimental group taking denosumab and the placebo control group, calculated as a percentage, in each of DeLee and Charnley's Zones 1 through 3, periprosthetic acetabulum.

Exploratory objectives will be to assess difference in loss of bone mineral density in the contralateral, or non-operated femur for both experimental and control groups, and to determine the role that covariates such as weight, gender, age, baseline BMD, and implant type have on percent change in BMD at 12 months.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Southern California
• Collaborator: Orthopaedic Institute for Children
• Treatments: Denosumab

Criteria

Inclusion Criteria:

• Inclusion criteria will allocate patients undergoing elective total hip replacement due to osteoarthritis. The prosthetic device will be a standard, non-cemented tapered total hip replacement, such as an Alloclassic® (Zimmer, Inc., Warsaw, IN) or a similarly shaped implant of the same material (titanium alloy) such as the Summit Hip (Depuy, Inc., Warsaw, IN). Subjects will be between 55 and 75 years of age. Both genders will be included. Prior to surgery, creatinine clearance, calcium, and vitamin D will be checked. Creatinine clearance rates must be above 30 ml/min, vitamin D serum levels must be greater than 12 ng/ml, and patients cannot be hypocalcemic. If vitamin D serum levels are below normal (30ng/ml) the 1000 mg of calcium and at least 1000 Units of vitamin D, recommended by the surgeon at the time of operation will likely be sufficient to correct this problem.

Exclusion Criteria:

• Current use of medications that may affect bone and mineral metabolism (e.g., glucocorticoids, diuretics, estrogen, oral contraceptives, tamoxifen, bisphosphonates, raloxifene, calcitonin, PTH, anticonvulsants, immunosuppressants), and subjects with a history of any disease that affects bone and mineral metabolism (e.g., thyrotoxicosis, hyperparathyroidism, hypocalcemia hypoparathyroidism, chronic renal failure, Cushing's disease, rheumatoid arthritis, hematological disease, alcohol abuse > 3 drinks a day), cancer. Additionally, patients who are taking immunosuppressants will be excluded. Patients who have been treated with anti-TNF in the past 3 months will be excluded. Patients with hypocalcemia or patients who have used bisphosphonates in the 2-3 years prior to the surgery will be excluded. Additionally, patients with creatinine clearance rates below 30 ml/minwill be excluded, as will patients with severe vitamin D deficiencies (<12 ng/ml). Patients with decreased hepatic function as measured by AST, ALT, Alkaline Phosphatase or Total Bilirubin will be excluded from the study. Patients who have had any solid organ or bone marrow transplants will be excluded. Patients who have a history of malignancy within the past 5 years, with the exception of basal cell carcinoma or cervical carcinoma in situ, will be excluded. Additionally, as the incidence of serious infections may be higher in patients treated with denosumab, patients with poorly controlled diabetes/HbA1C will be excluded.