Ignite Creation Date:
2025-12-25 @ 3:02 AM
Ignite Modification Date:
2026-02-25 @ 8:59 PM
Study NCT ID:
NCT03868033
Status:
COMPLETED
Last Update Posted:
2024-04-23
First Post:
2019-03-06
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Denosumab Sequential Therapy
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D010024', 'term': 'Osteoporosis'}], 'ancestors': [{'id': 'D001851', 'term': 'Bone Diseases, Metabolic'}, {'id': 'D001847', 'term': 'Bone Diseases'}, {'id': 'D009140', 'term': 'Musculoskeletal Diseases'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077211', 'term': 'Zoledronic Acid'}, {'id': 'D000069448', 'term': 'Denosumab'}], 'ancestors': [{'id': 'D004164', 'term': 'Diphosphonates'}, {'id': 'D063065', 'term': 'Organophosphonates'}, {'id': 'D009943', 'term': 'Organophosphorus Compounds'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D007093', 'term': 'Imidazoles'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D061067', 'term': 'Antibodies, Monoclonal, Humanized'}, {'id': 'D000911', 'term': 'Antibodies, Monoclonal'}, {'id': 'D000906', 'term': 'Antibodies'}, {'id': 'D007136', 'term': 'Immunoglobulins'}, {'id': 'D007162', 'term': 'Immunoproteins'}, {'id': 'D001798', 'term': 'Blood Proteins'}, {'id': 'D011506', 'term': 'Proteins'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D012712', 'term': 'Serum Globulins'}, {'id': 'D005916', 'term': 'Globulins'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 101}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2019-04-12', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-09', 'completionDateStruct': {'date': '2023-12-31', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2024-04-21', 'studyFirstSubmitDate': '2019-03-06', 'studyFirstSubmitQcDate': '2019-03-07', 'lastUpdatePostDateStruct': {'date': '2024-04-23', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2019-03-08', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2023-07-01', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Changes of lumbar spine, total hip and femoral neck bone mineral density', 'timeFrame': 'baseline, 1 year, 2 year', 'description': 'Changes of lumbar spine, total hip and femoral neck bone mineral density from baseline'}], 'secondaryOutcomes': [{'measure': 'Change of bone turnover marker', 'timeFrame': 'baseline, 6 months, 12 months, 15 months, 18 months, 24 months', 'description': 'Changes of bone turnover marker, including C-terminal telopeptide of type I collagen (CTX) and propeptide of procollagen type I (P1NP)'}, {'measure': 'Clinical osteoporotic fracture', 'timeFrame': 'baseline, 1 year, 2 year', 'description': 'Incidence of clinical osteoporotic fracture'}]}, 'oversightModule': {'isUsExport': True, 'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Osteoporosis', 'Denosumab', 'Zoledronate', 'Bone mineral density'], 'conditions': ['Osteoporosis']}, 'referencesModule': {'references': [{'pmid': '39527056', 'type': 'DERIVED', 'citation': 'Lee CC, Wang CY, Yen HK, Hung CC, Lai CY, Hu MH, Wang TM, Li CY, Fu SH. Zoledronate Sequential Therapy After Denosumab Discontinuation to Prevent Bone Mineral Density Reduction: A Randomized Clinical Trial. JAMA Netw Open. 2024 Nov 4;7(11):e2443899. doi: 10.1001/jamanetworkopen.2024.43899.'}, {'pmid': '34568375', 'type': 'DERIVED', 'citation': 'Lee CC, Wang CY, Hung CC, Huang CC, Li CY, Chen HY, Chang YL, Tseng WJ, Wang TM, Yang RS, Wong TH, Fu SH. A Multi-Institutional Randomized Controlled Trial to Investigate Whether Zoledronate Prevents Bone Loss After Discontinuation of Denosumab: The Study Protocol of Denosumab Sequential Therapy (DST) Trial. Front Med (Lausanne). 2021 Sep 8;8:717168. doi: 10.3389/fmed.2021.717168. eCollection 2021.'}]}, 'descriptionModule': {'briefSummary': "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.", 'detailedDescription': "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.\n\nAlthough 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.\n\nHow 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.\n\nWe want to verify if zoledronic acid could be used as a sequential therapy after denosumab to prevent rapid bone loss by randomized clinical trial."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '80 Years', 'minimumAge': '50 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Postmenopausal women\n2. Men \\>50-year-old\n3. After Denosumab treatment ≥ 2 years due to osteoporosis\n\nExclusion Criteria:\n\n1. Patientshadeverusedantiosteoporosismedications other than Dmab\n2. Estimated glomerular filtration rate \\<35 ml/min.\n3. Malignancy\n4. Continuous steroid treatment, hormone therapy or other medical treatment affecting bone metabolism\n5. Secondary osteoporosis\n6. Metabolic bone diseases\n7. Contraindications to ZOL\n8. Patients older than 80 years old\n9. Hypocalcemia'}, 'identificationModule': {'nctId': 'NCT03868033', 'acronym': 'DST', 'briefTitle': 'Denosumab Sequential Therapy', 'organization': {'class': 'OTHER', 'fullName': 'National Taiwan University Hospital'}, 'officialTitle': 'Department of Orthopedics, National Taiwan University Hospital', 'orgStudyIdInfo': {'id': '201811067MIPC'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Continuous Denosumab', 'description': 'Continuous anti-resorptive therapy by Denosumab for 2 years', 'interventionNames': ['Drug: Denosumab']}, {'type': 'EXPERIMENTAL', 'label': 'Zoledronic acid to Denosumab', 'description': 'treat with Zoledronic acid for one year and then shift to Denosumab for another one year', 'interventionNames': ['Drug: Zoledronic Acid', 'Drug: Denosumab']}, {'type': 'EXPERIMENTAL', 'label': 'Continuous Zoledronic acid', 'description': 'Continuous anti-resorptive therapy by Zoledronic acid for 2 years', 'interventionNames': ['Drug: Zoledronic Acid']}, {'type': 'EXPERIMENTAL', 'label': 'Zoledronic acid to observation', 'description': 'treat with Zoledronic acid for one year and then close follow up by bone turn over marker.\n\nresume another dose of Zoledronic acid if elevated CTX level above normal range', 'interventionNames': ['Drug: Zoledronic Acid']}], 'interventions': [{'name': 'Zoledronic Acid', 'type': 'DRUG', 'otherNames': ['Aclasta'], 'description': 'Use Zoledronic acid as a sequential therapy after denosumab treatment for more than 2 years', 'armGroupLabels': ['Continuous Zoledronic acid', 'Zoledronic acid to Denosumab', 'Zoledronic acid to observation']}, {'name': 'Denosumab', 'type': 'DRUG', 'otherNames': ['Prolia'], 'description': 'Continuous Denosumab treatment in arm 1 for two years or as a 2nd year treatment in arm 2 for one year', 'armGroupLabels': ['Continuous Denosumab', 'Zoledronic acid to Denosumab']}]}, 'contactsLocationsModule': {'locations': [{'zip': '64041', 'city': 'Taipei', 'state': 'N/A = Not Applicable', 'country': 'Taiwan', 'facility': 'Department of Orthopedics, National Taiwan University Hospital', 'geoPoint': {'lat': 25.05306, 'lon': 121.52639}}], 'overallOfficials': [{'name': 'Shau-Huai Fu, doctor', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Department of Orthopedics, National Taiwan University Hospital Yunlin Branch'}, {'name': 'Chia-Che Lee', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Department of Orthopedics, National Taiwan University Hospital'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'National Taiwan University Hospital', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}