Trial record 20 of 69 for:    Open Studies | "Parathyroid Diseases"

Denosumab in Primary Hyperparathyroidism

This study is currently recruiting participants.
Verified February 2013 by Columbia University
Sponsor:
Collaborators:
Amgen
Information provided by (Responsible Party):
John P. Bilezikian, Columbia University
ClinicalTrials.gov Identifier:
NCT01558115
First received: March 16, 2012
Last updated: February 12, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Primary Hyperparathyroidism
Drug: Denosumab
Other: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Denosumab in Primary Hyperparathyroidism

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Change in Bone Mineral Density (BMD) at the lumbar spine [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    Percent change from baseline in BMD at the lumbar spine, as measured by Dual-emission X-ray absorptiometry (DXA) scan at 12 months


Secondary Outcome Measures:
  • Change in Bone Mineral Density (BMD) at the distal 1/3 radius [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Percent change from baseline in BMD at the distal 1/3 radius, as measured by Dual-emission X-ray absorptiometry (DXA) scan at 12 months

  • Change in Bone Mineral Density (BMD) at the hip [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Percent change from baseline in BMD at the hip, as measured by Dual-emission X-ray absorptiometry (DXA) scan at 12 months


Estimated Enrollment: 28
Study Start Date: January 2012
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Denosumab Drug: Denosumab

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 28 subjects will be randomly allocated (1:1) into treatment and placebo arms with the placebo group receiving a subcutaneous injection of vehicle only. 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 (14 patients): Receive active drug for year 1 and year 2 of the study

Group #2 (14 patients): Receive placebo for year 1 and active drug for year 2 of the study

Other Names:
  • Prolia
  • Xgeva
Placebo Comparator: Placebo
Vehicle only
Other: Placebo

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 28 subjects will be randomly allocated (1:1) into treatment and placebo arms with the placebo group receiving a subcutaneous injection of vehicle only. 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 (14 patients): Receive active drug for year 1 and year 2 of the study

Group #2 (14 patients): Receive placebo for year 1 and active drug for year 2 of the study


Detailed Description:

PTH has both catabolic and anabolic properties, and under normal circumstances, PTH in PHPT is catabolic for bone at the cortical skeleton. Recently, evidence for a direct role of PTH on RANKL expression and osteoclastogenesis in vivo was obtained using mice lacking a distant transcriptional enhancer of the RANKL gene that confers responsiveness to PTH. These observations, supported by additional cross-sectional studies in human subjects make a compelling argument that the catabolic actions of PTH are mediated by RANKL-mediated bone resorption.

The investigators now propose a proof of concept study to test the hypothesis that in PHPT, inhibition of the RANK-L pathway will unmask the anabolic potential of PTH. A therapeutic agent that redirects the actions of PTH in PHPT from one that is primarily catabolic to an anabolic one would fulfill this proof of concept. The investigators hypothesize that Denosumab, a human IgG antibody that binds to and inactivates RANKL, will convert skeletal actions of PTH from catabolic to anabolic in primary hyperparathyroidism.

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01558115

Contacts
Contact: Wendy Fan, MPH 212-305-2900 wf2159@columbia.edu
Contact: Megan E Romano, BA 212-304-7254 mr647@columbia.edu

Locations
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Wendy Fan, MPH    212-305-2900    wf2159@columbia.edu   
Contact: Megan E Romano, BA    212-304-7254    mr647@columbia.edu   
Principal Investigator: John P Bilezikian, MD         
Sponsors and Collaborators
John P. Bilezikian
Amgen
Investigators
Principal Investigator: John P Bilezikian, MD Columbia University
  More Information

No publications provided

Responsible Party: John P. Bilezikian, Dorothy L. and Daniel H. Silberberg Professor of Medicine and Professor of Pharmacology, Columbia University
ClinicalTrials.gov Identifier: NCT01558115     History of Changes
Other Study ID Numbers: AAAF2568, R01DK032333, 20090741
Study First Received: March 16, 2012
Last Updated: February 12, 2013
Health Authority: United States: Institutional Review Board
United States: Federal Government

Keywords provided by Columbia University:
Columbia University
Primary hyperparathyroidism
Low bone density
Denosumab
Prolia

Additional relevant MeSH terms:
Hyperparathyroidism
Hyperparathyroidism, Primary
Parathyroid Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on April 16, 2014