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Trial record 1 of 1 for:    NCT02903446
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Denosumab In Addition To Intense Urate-Lowering Therapy for Bone Erosions

This study is currently recruiting participants.
Verified September 2017 by Angelo L. Gaffo, University of Alabama at Birmingham
Sponsor:
ClinicalTrials.gov Identifier:
NCT02903446
First Posted: September 16, 2016
Last Update Posted: September 28, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
University of Auckland, New Zealand
Information provided by (Responsible Party):
Angelo L. Gaffo, University of Alabama at Birmingham
  Purpose
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.

Condition Intervention Phase
Gout Drug: Denosumab Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Denosumab In Addition To Intense Urate-Lowering Therapy for Bone Erosions in Gout: A Pilot Study

Resource links provided by NLM:


Further study details as provided by Angelo L. Gaffo, University of Alabama at Birmingham:

Primary Outcome Measures:
  • CT bone erosion score [ Time Frame: 12 months ]
    Change in the foot CT bone erosion score from baseline to 12 months


Secondary Outcome Measures:
  • Decrease in bone reabsorption [ Time Frame: 12 months ]
    Decrease in bone reabsorption as measured by serum CTX levels over 12 months

  • Subject reported functional status (disability) [ Time Frame: 12 months ]
    Subject reported functional status (disability) by Health Assessment Questionnaire (HAQ) will be assessed from baseline over 12 months

  • Subject reported change in physical and mental health [ Time Frame: 12 months ]
    Subject reported change in physical and mental health by Short Form Health Survey (SF-12) scores assessed from baseline over 12 months

  • Assessment of pain [ Time Frame: 12 months ]
    Assessment of pain score by visual analogue scale (VAS) reported from baseline over 12 months


Estimated Enrollment: 20
Actual Study Start Date: February 1, 2017
Estimated Study Completion Date: May 2018
Estimated Primary Completion Date: May 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Intervention
Denosumab 60 mg administered subcutaneously (SC) every 6 months for a year + urate lowering therapy (ULT) standard of care
Drug: Denosumab
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
Other Name: Prolia
No Intervention: Control
Standard urate lowering therapy

Detailed Description:

A recently published clinical trial with zoledronic acid failed to show an effect in improving bone erosions among individuals with chronic tophaceous gout, despite improvements in bone mineral density (BMD) and bone turnover markers. However, it is known that increased numbers of osteoclasts (cells that absorb bone tissue during growth and healing) in patients with tophaceous gout are most likely a result of enhanced osteoclast activity as these patients also have higher circulating levels of the protein receptor activator of nuclear factor kappa-B ligand (RANKL). RANKL has been identified to affect the immune system and control bone regeneration and remodeling.

Furthermore, peripheral blood cells and synovial fluid cells taken from patients with erosive gout preferentially formed osteoclast-like cells in the presence of RANKL. The number of osteoclasts formed significantly correlates with the number of tophi in gout patients.

Denosumab (Prolia®) is a fully human monoclonal antibody with a high affinity for RANKL that can bind and neutralize the activity of human RANKL. Given the relevance of RANKL in the mechanism of gouty erosions,a central hypothesis of this pilot study is that denosumab is more likely to precisely target RANKL and the mechanism of gouty erosions than zoledronic acid.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02903446


Contacts
Contact: Angelo L Gaffo, MD 205-934-0981 agaffo@uabmc.edu
Contact: Phillip J Foster, MPH 2059966086 pjfoster@uabmc.edu

Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Jeff Foster, MPH    205-996-6086    pjfoster@uabmc.edu   
Principal Investigator: Angelo L Gaffo, MD, MPH         
Sponsors and Collaborators
University of Alabama at Birmingham
University of Auckland, New Zealand
  More Information

Responsible Party: Angelo L. Gaffo, Principal Investigator, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT02903446     History of Changes
Other Study ID Numbers: F160315004
First Submitted: September 13, 2016
First Posted: September 16, 2016
Last Update Posted: September 28, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Denosumab
Uric Acid
Bone Density Conservation Agents
Physiological Effects of Drugs
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents