Denosumab in Primary Hyperparathyroidism

• Status: Completed
• Trial end date: 2014-10-01
• Target enrollment: 0
• Participant gender: Female

Summary

Primary hyperparathyroidism (PHPT), a disease characterized by excess parathyroid hormone (PTH) and high blood calcium, is one of the most common endocrine disorders. PHPT is seen most often in postmenopausal women. Many patients with PHPT have low bone mineral density (BMD) when bone mass is measured by dual energy x-ray absorptiometry (DXA), primarily at the forearm. There is currently no effective medical therapy which increases bone density at the forearm in patients with PHPT.

PTH both builds and breaks down bone, and the pathways by which PTH mediates these actions are beginning to be identified. Prior research suggests that RANKL, a molecule important in bone metabolism, responds to PTH, and that if the RANKL is inactivated, PTH is shifted towards building bone. The investigators will study the effect of Denosumab, a therapeutic agent that binds to and inactivates RANKL, in 28 postmenopausal women with PHPT. Our hypothesis is that Denosumab will increase bone mineral density in primary hyperparathyroidism.

The study will last two years, and subjects will be randomly assigned to receive either placebo or Denosumab for the first year of the study. In the second year, all subjects will receive Denosumab. Denosumab (60 mg) or placebo will be given every 6 months by an injection just under the skin. Study procedures performed will include bone mineral density tests by DXA, high-resolution peripheral quantitative computed tomography (HR-pQCT) scans, and assessments of biochemical markers of calcium metabolism and bone turnover using both blood and urine samples of subjects with PHPT.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: John P. Bilezikian
• Collaborators: Amgen; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Institutes of Health (NIH)
• Treatments: Denosumab

Criteria

Inclusion Criteria:

• Confirmed hypercalcemic PHPT in postmenopausal women with serum calcium >10.2 mg/dL and < 12.0 mg/dL (nl: 8.6-10.2)

• T-score between -1.5 and -2.5 at any site. If the T-score is <-2.5, patients become candidates for parathyroid surgery. They will be enrolled only if they refuse the parathyroid surgery

Exclusion Criteria:

• 25-hydroxyvitamin D level < 20 ng/ml

• Previous use of the bisphosphonate zoledronic acid (ever), alendronate or risedronate (within 12 months) or ibandronate (within 6 months)

• Current use of PTH, glucocorticoids, SERMS, estrogen (other than vaginal), calcitonin or pharmacological amounts of calcitriol Current or previous use of cinacalcet (within 6 months)

• Hyperthyroidism

• Rheumatoid arthritis or any other inflammatory joint disease

• Paget's disease of bone

• Malabsorption

• T-score <-3.5 at any site

• Signs of symptomatic PHPT (e.g, kidney stones within the past 5 years; fragility fracture within the past 2 years)

• Physical or mental handicapping condition that precludes ability to complete the protocol and/or provide informed consent.

• Subjects on Antiviral HIV therapy or subjects with compromised immune systems

• Premenopausal women or men

• Stage 5 CKD or anyone on dialysis

• Creatinine clearance < 30 cc/min unless the patient is not a candidate for surgery or if the patient refuses surgery