Denosumab In Addition To Intense Urate-Lowering Therapy for Bone Erosions
Condition: Gout
MeSH terms: Gout
Intervention: Denosumab
Intervention description: Participants will be randomized (1:1) allocation to denosumab 60 mg administered subcutaneously (SC) every 6 months for a year + ULT standard of care OR ULT standard of care therapy
Intervention MeSH terms: Denosumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 30 Years
Healthy volunteers: No

Summary:

      Bone erosions are a common manifestation and feature of structural damage in severe/chronic
      tophaceous gout. Management of this destructive and often debilitating gout complication has
      focused exclusively on urate-lowering therapy (ULT) to reduce frequency of gout attacks, but
      little attention has been given to prevention or reversal of gout related bone erosions and
      other structural damage to bone caused by gout. Since there is no known effective treatment
      to attenuate or improve structural damage caused by gout, we propose a pilot, controlled,
      proof-of-concept study in which denosumab, an FDA approved medication for the treatment of
      bone loss, will be added to standard ULT in 20 patients with erosive gout.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age 30 years or older and able to provide informed consent

          -  Diagnosis of gout according to the American College of Rheumatology (ACR) / European
             League Against Rheumatism (EULAR) classification criteria

          -  Radiographic foot bone erosion attributable to gout and confirmed by a radiologist

          -  Serum urate of ≤ 5 mg/dL (300 µmol/L) or less*

        Exclusion Criteria:

          -  Treatment with bisphosphonates in the preceding 2 years

          -  Any prior treatment with denosumab

          -  Women of childbearing potential, who are not currently using birth control, are
             pregnant, planning to become pregnant, or are breast-feeding

          -  Men planning to conceive in the next 12 months

          -  Unstable systemic medical condition

          -  Uncontrolled hyperthyroidism

          -  Uncontrolled hypothyroidism

          -  History of Addison disease

          -  History of osteomalacia

          -  History of osteonecrosis of the jaw (ONJ)

          -  History of atypical femur fracture

          -  History of tooth extraction, jaw surgery, dental implants, or other dental surgery
             within the prior 6 months

          -  History of anorexia nervosa, bulimia (by history or physical) or obvious malnutrition.

          -  Invasive dental work planned in the next 2 years

          -  History of Paget's disease of bone

          -  Other bone diseases which affect bone metabolism

          -  Vitamin D deficiency [25(OH) vitamin D level < 20 ng/mL (<49.9 nmol/L)]†

          -  Hypercalcemia

          -  Elevated transaminases ≥ 2.0 x upper limit of normal (ULN)

          -  Elevated total bilirubin > 1.5x ULN

          -  History of any solid organ or bone marrow transplant

          -  Malignancy within the last 5 years (except cervical carcinoma in situ or basal cell
             carcinoma)

          -  Hypocalcemia

          -  Poorly tolerant of ULT including allopurinol, febuxostat, or probenecid

          -  Estimated glomerular filtration rate < 30 mL/minute/1.73 m^2

          -  Current use of any biological therapy (eg. infliximab, etanercept, adalimumab, etc.)

          -  Treatment history with pegloticase or another recombinant uricase

          -  Recipient of an investigational drug within 4 weeks prior to study drug administration
             or plans to take an investigational agent during the study