NCT02499237

Brief Summary

In contrast with bisphosphonates,discontinuation of denosumab results in gradual loss of bone mineral density gains. The investigators aim to evaluate whether in patients treated with denosumab, a single zoledronic acid infusion would prevent the anticipated bone loss.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
57

participants targeted

Target at P25-P50 for phase_4

Timeline
Completed

Started Jul 2015

Typical duration for phase_4

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2015

Completed
13 days until next milestone

First Submitted

Initial submission to the registry

July 14, 2015

Completed
2 days until next milestone

First Posted

Study publicly available on registry

July 16, 2015

Completed
3.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2018

Completed
25 days until next milestone

Study Completion

Last participant's last visit for all outcomes

November 26, 2018

Completed
Last Updated

March 11, 2019

Status Verified

March 1, 2019

Enrollment Period

3.3 years

First QC Date

July 14, 2015

Last Update Submit

March 8, 2019

Conditions

Keywords

osteoporosisdenosumabzoledronic acidbone mineral densitybone markers

Outcome Measures

Primary Outcomes (1)

  • bone mineral density of the lumbar spine

    differences between the 2 arms in the changes of lumbar spine bone mineral density measured by dual-energy X-ray absorptiometry

    from 12 to 24 months

Secondary Outcomes (5)

  • bone mineral density of the femoral neck

    from 12 to 24 months

  • C-terminal telopeptide of type I collagen

    from 12 to 15, 18, 24 months

  • propeptide of procollagen type I

    from 12 to 15, 18, 24 months

  • bone mineral density of the lumbar spine

    from baseline to 12 months

  • bone mineral density of the femoral neck

    from baseline to 12 months

Study Arms (2)

Denosumab

ACTIVE COMPARATOR

Patients with low bone mass, being treated only with denosumab in the past, who will receive another year of treatment with denosumab and subsequently discontinue treatment for one year

Drug: Denosumab

Denosumab plus zoledronic acid

EXPERIMENTAL

Patients with low bone mass, being treated only with denosumab in the past, who will receive a single infusion of zoledronic acid and subsequently discontinue treatment for another year

Drug: Zoledronic acid

Interventions

Treatment of low bone mass with subcutaneous injections of denosumab 60 mg every 6 months for one year

Also known as: Prolia
Denosumab

Treatment of low bone mass with a single infusion of zoledronic acid 5 mg for one year

Also known as: Aclasta
Denosumab plus zoledronic acid

Eligibility Criteria

Age50 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • postmenopausal women
  • osteopenic (T-score \> -2.5 but \< -1.0) after treatment with denosumab

You may not qualify if:

  • secondary osteoporosis;
  • diseases that could affect bone metabolism;
  • medications that could affect bone metabolism;
  • history of any antiosteoporotic treatment other than denosumab prior to randomization
  • severe liver or kidney disease (creatinine clearance \< 60ml/min/1.73m2)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

251 Airforce & VA General Hospital

Athens, 11525, Greece

Location

424 General Military Hospital

Thessaloniki, 56429, Greece

Location

Related Publications (5)

  • Miller PD, Bolognese MA, Lewiecki EM, McClung MR, Ding B, Austin M, Liu Y, San Martin J. Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: a randomized blinded phase 2 clinical trial. Bone. 2008 Aug;43(2):222-229. doi: 10.1016/j.bone.2008.04.007. Epub 2008 Apr 26.

    PMID: 18539106BACKGROUND
  • Bone HG, Bolognese MA, Yuen CK, Kendler DL, Miller PD, Yang YC, Grazette L, San Martin J, Gallagher JC. Effects of denosumab treatment and discontinuation on bone mineral density and bone turnover markers in postmenopausal women with low bone mass. J Clin Endocrinol Metab. 2011 Apr;96(4):972-80. doi: 10.1210/jc.2010-1502. Epub 2011 Feb 2.

    PMID: 21289258BACKGROUND
  • Black DM, Bauer DC, Schwartz AV, Cummings SR, Rosen CJ. Continuing bisphosphonate treatment for osteoporosis--for whom and for how long? N Engl J Med. 2012 May 31;366(22):2051-3. doi: 10.1056/NEJMp1202623. Epub 2012 May 9. No abstract available.

    PMID: 22571169BACKGROUND
  • Whitaker M, Guo J, Kehoe T, Benson G. Bisphosphonates for osteoporosis--where do we go from here? N Engl J Med. 2012 May 31;366(22):2048-51. doi: 10.1056/NEJMp1202619. Epub 2012 May 9. No abstract available.

    PMID: 22571168BACKGROUND
  • Anastasilakis AD, Polyzos SA, Yavropoulou MP, Appelman-Dijkstra NM, Ntenti C, Mandanas S, Papatheodorou A, Makras P. Comparative Effect of Zoledronate at 6 Versus 18 Months Following Denosumab Discontinuation. Calcif Tissue Int. 2021 May;108(5):587-594. doi: 10.1007/s00223-020-00785-1. Epub 2021 Jan 2.

MeSH Terms

Conditions

Osteoporosis, PostmenopausalOsteoporosis

Interventions

DenosumabZoledronic Acid

Condition Hierarchy (Ancestors)

Bone Diseases, MetabolicBone DiseasesMusculoskeletal DiseasesMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsDiphosphonatesOrganophosphonatesOrganophosphorus CompoundsOrganic ChemicalsImidazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Officials

  • Athanasios D Anastasilakis, PhD

    424 General Military Hospital, Thessaloniki, Greece

    PRINCIPAL INVESTIGATOR
  • Polyzois Makras, PhD

    251 Airforce and VA General Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Consultant of Endocrinology

Study Record Dates

First Submitted

July 14, 2015

First Posted

July 16, 2015

Study Start

July 1, 2015

Primary Completion

November 1, 2018

Study Completion

November 26, 2018

Last Updated

March 11, 2019

Record last verified: 2019-03

Locations