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Denosumab Sequential Therapy (DST)

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ClinicalTrials.gov Identifier: NCT03868033
Recruitment Status : Recruiting
First Posted : March 8, 2019
Last Update Posted : March 11, 2019
Sponsor:
Information provided by (Responsible Party):
National Taiwan University Hospital

Brief Summary:
Denosumab is a potent anti-resorptive agent and is now widely used in the treatment of osteoporosis. Although denosumab has excellent effect to increase bone mass and prevent fracture in FREEDOM study with very low complications, even up to ten years, it's effect is reversible. After holding the drug, circulating denosumab levels fall rapidly, and bone resorption reaching twice baseline levels for about 6 months. How to prevent bone loss after denosumab therapy is an important issue, especially when considering the compliance, persistence, or other comorbidities of the patient. We want to verify if zoledronic acid could be used as a sequential therapy after denosumab to prevent rapid bone loss by randomized clinical trial.

Condition or disease Intervention/treatment Phase
Osteoporosis Drug: Zoledronic Acid Drug: Denosumab Phase 4

Detailed Description:

Denosumab is a monoclonal antibody directed against the protein RANK-L, the principal regulator of osteoclast development. Thus, it acts as a potent anti-resorptive agent and is now widely used in the treatment of osteoporosis. Because it's easily to be used with very low risk of complications, patient has better compliance and persistence of denosumab than bisphosphonates. It's market share increasing very rapidly in Taiwan.

Although denosumab has excellent effect to increase bone mass and prevent fracture in FREEDOM study with very low complications, even up to ten years, it's effect is reversible. After holding the drug, circulating denosumab levels fall rapidly, and bone resorption reaching twice baseline levels for about 6 months. Over the first 12 months off therapy, all the bone density gained on treatment is lost4. According to previous meta-analysis study, although the persistence of denosumab therapy is better than bisphosphonates, only 62% patients keep the treatment after two years. We could image how low the persistence is after five-year or ten-year treatment in the real world.

How to prevent bone loss after denosumab therapy is an important issue, especially when considering the compliance, persistence, or other comorbidities of the patient. There is only one randomized controlled trial dealing with this problem, although the primary goal of the study is designed to compare the compliance and persistence1. After switching from denosumab to alendronate for one year, bone mineral density does not decrease rapidly, although there is mild elevation of bone turn over marker.

We want to verify if zoledronic acid could be used as a sequential therapy after denosumab to prevent rapid bone loss by randomized clinical trial.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Department of Orthopedics, National Taiwan University Hospital
Estimated Study Start Date : March 7, 2019
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Continuous Denosumab
Continuous anti-resorptive therapy by Denosumab for 2 years
Drug: Denosumab
Continuous Denosumab treatment in arm 1 for two years or as a 2nd year treatment in arm 2 for one year
Other Name: Prolia

Experimental: Zoledronic acid to Denosumab
treat with Zoledronic acid for one year and then shift to Denosumab for another one year
Drug: Zoledronic Acid
Use Zoledronic acid as a sequential therapy after denosumab treatment for more than 2 years
Other Name: Aclasta

Drug: Denosumab
Continuous Denosumab treatment in arm 1 for two years or as a 2nd year treatment in arm 2 for one year
Other Name: Prolia

Experimental: Continuous Zoledronic acid
Continuous anti-resorptive therapy by Zoledronic acid for 2 years
Drug: Zoledronic Acid
Use Zoledronic acid as a sequential therapy after denosumab treatment for more than 2 years
Other Name: Aclasta

Experimental: Zoledronic acid to observation

treat with Zoledronic acid for one year and then close follow up by bone turn over marker.

resume another dose of Zoledronic acid if elevated CTX level above normal range

Drug: Zoledronic Acid
Use Zoledronic acid as a sequential therapy after denosumab treatment for more than 2 years
Other Name: Aclasta




Primary Outcome Measures :
  1. Changes of total hip and femoral neck bone mineral density [ Time Frame: baseline, 1 year, 2 year ]
    Changes of total hip and femoral neck bone mineral density from baseline


Secondary Outcome Measures :
  1. Change in lumbar spine bone mineral density [ Time Frame: baseline, 1 year, 2 year ]
    Change in lumbar spine bone mineral density from baseline

  2. Change of bone turnover marker [ Time Frame: baseline, 6 months, 1 year, 1.5 years, 2 year ]
    Changes of bone turnover marker, including C-terminal telopeptide of type I collagen (CTX) and propeptide of procollagen type I (P1NP)

  3. Clinical osteoporotic fracture [ Time Frame: baseline, 1 year, 2 year ]
    Incidence of clinical osteoporotic fracture



Information from the National Library of Medicine

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Ages Eligible for Study:   55 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Postmenopausal women
  2. Men >50-year-old
  3. After Denosumab treatment ≥ 2 years due to osteoporosis

Exclusion Criteria:

  1. secondary osteoporosis
  2. metabolic bone disease
  3. cancer history
  4. continuous steroid therapy
  5. hormone replacement therapy
  6. ever used any other kind of anti-resorptive treatment

6.estimated Glomerular filtration rate< 35 mL/min 7.allergy to Zoledronic acid 8.hypocalcaemia 9.any contraindications to use Zoledronic acid


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): NCT03868033


Contacts
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Contact: Shau-Huai Fu +886972655734 b90401045@gmail.com

Locations
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Taiwan
Department of Orthopedics, National Taiwan University Hospital Recruiting
Taipei, N/A = Not Applicable, Taiwan, 64041
Contact: Shau-Huai Fu    +886972655734    b90401045@gmail.com   
Sponsors and Collaborators
National Taiwan University Hospital
Investigators
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Principal Investigator: Shau-Huai Fu, doctor Department of Orthopedics, National Taiwan University Hospital Yunlin Branch
Principal Investigator: Chia-Che Lee Department of Orthopedics, National Taiwan University Hospital

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Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT03868033     History of Changes
Other Study ID Numbers: 201811067MIPC
First Posted: March 8, 2019    Key Record Dates
Last Update Posted: March 11, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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.: Yes

Keywords provided by National Taiwan University Hospital:
Osteoporosis
Denosumab
Zoledronate
Bone mineral density

Additional relevant MeSH terms:
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Osteoporosis
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Metabolic Diseases
Zoledronic Acid
Denosumab
Bone Density Conservation Agents
Physiological Effects of Drugs