Denosumab in Primary Hyperparathyroidism
Condition: Primary Hyperparathyroidism
MeSH terms: Hyperparathyroidism; Hyperparathyroidism, Primary
Intervention: Denosumab; Placebo
Intervention description: The dose of denosumab is 60 mg every 6 months by subcutaneous injection.
The 52 subjects will be randomly allocated (2:1) into treatment and placebo arms with the placebo group receiving a subcutaneous injection of vehicle in year 1. In year 2, those who were allocated to the study drug in year 1 will continue in year 2. Those who were allocated to placebo in year 1 will be crossed over to study drug in year 2.
Group # 1: Receive active drug for year 1 and year 2 of the study
Group #2: Receive placebo for year 1 and active drug for year 2 of the study; The dose of denosumab is 60 mg every 6 months by subcutaneous injection. The placebo group will receive vehicle injections at the same time interval.
The 52 subjects will be randomly allocated (2:1) into treatment and placebo arms with the placebo group receiving a subcutaneous injection of vehicle in year 1. In year 2, those who were allocated to the study drug in year 1 will continue in year 2. Those who were allocated to placebo in year 1 will be crossed over to study drug in year 2.
Group # 1: Receive active drug for year 1 and year 2 of the study
Group #2: Receive placebo for year 1 and active drug for year 2 of the study
Intervention MeSH terms: Denosumab
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 8.0
Sex: Female
Minimum age: 40 Years
Healthy volunteers: No
Keywords: Columbia University; Primary hyperparathyroidism; Low bone density; Denosumab; Prolia

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.
    

Eligibility 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 Chronic Kidney Disease (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