Postmenopausal OsteoporosisPhase 4AfterDmabNCT02499237
Zoledronic Acid to Maintain Bone Mass After Denosumab Discontinuation
A Phase 4 study testing Denosumab and Zoledronic acid in people with Postmenopausal Osteoporosis, run by 424 General Military Hospital at 2 sites in Greece.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 years and older, women only
- Conditions the study is for
- Postmenopausal Osteoporosis
- What is being tested?
- Denosumab and Zoledronic acid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 2 sitesGreece
- Study dates
- Jul 2015to 26 Nov 2018
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- postmenopausal women
- osteopenic (T-score > -2.5 but < -1.0) after treatment with denosumab
Who cannot join
- 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)
Trial locations and contacts
2 sites in 1 country.
Greece2 sites
251 Airforce & VA General Hospital
Athens, 11525
424 General Military Hospital
Thessaloniki, 56429
About this study
Official title: The Effect of Zoledronic Acid Infusion in the Bone Loss Observed Following Denosumab Discontinuation in Postmenopausal Women With Low Bone Mass
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.
Read the detailed description
Discontinuation of denosumab results in a rebound rise of bone turnover markers and gradual loss of the achieved bone mineral density gains. In contrast, bisphosphonates, such as zoledronic acid, remain within the skeleton acting for several months or even years after discontinuation while maintaining bone mineral density despite the cessation of treatment. In this study, the investigators aim to evaluate changes in bone mineral density of the lumbar spine and the femoral neck, as well as in bone turnover markers one year after treatment discontinuation both in denosumab-treated women and in denosumab-treated women who switched to zoledronic acid infusion one year before treatment discontinuation.
- Conditions
- Postmenopausal Osteoporosis
- Being tested
- Denosumab, Zoledronic acid
- Keywords
- osteoporosis, denosumab, zoledronic acid, bone mineral density, bone markers
- Medical subject headings
- Osteoporosis, Postmenopausal, Osteoporosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DenosumabDrug
Also called Prolia
Treatment of low bone mass with subcutaneous injections of denosumab 60 mg every 6 months for one year
Zoledronic acidDrug
Also called Aclasta
Treatment of low bone mass with a single infusion of zoledronic acid 5 mg for one year
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Zoledronic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: from 12 to 24 months
Secondary outcomes (5)
bone mineral density of the femoral neck
differences between the 2 arms in the changes of femoral neck bone mineral density measured by dual-energy X-ray absorptiometry
Measured: from 12 to 24 months
C-terminal telopeptide of type I collagen
differences between the 2 arms in the changes of C-terminal telopeptide of type I collagen
Measured: from 12 to 15, 18, 24 months
propeptide of procollagen type I
differences between the 2 arms in the changes of propeptide of procollagen type I
Measured: from 12 to 15, 18, 24 months
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
Measured: from baseline to 12 months
bone mineral density of the femoral neck
differences between the 2 arms in the changes of femoral neck bone mineral density measured by dual-energy X-ray absorptiometry
Measured: from baseline to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2015 (estimated)
- Study startJul 2015
- Primary completionNov 2018
- Study completion26 Nov 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Postmenopausal OsteoporosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- 424 General Military Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- 251 Hellenic Air Force & VA General Hospital, Leiden University Medical Center
- Responsible party
- Principal investigator, Athanasios D. Anastasilakis, 424 General Military Hospital
- Investigators
- Athanasios D Anastasilakis, PhD, Principal investigator, 424 General Military Hospital, Thessaloniki, GreecePolyzois Makras, PhD, Principal investigator, 251 Airforce and VA General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02499237
- Sponsor's protocol ID
- AfterDmab
- Acronym
- AfterDmab
- Status last verified
- Mar 2019
- First submitted
- 14 Jul 2015
- Last updated
- 11 Mar 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 18539106Bone 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.
PubMed 21289258Black 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.
PubMed 22571169Whitaker 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.
PubMed 22571168Anastasilakis 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.
PubMed 33386953
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Zoledronic Acid Infusion in the Bone Loss Observed Following Denosumab Discontinuation in Postmenopausal Women With Low Bone Mass
- ClinicalTrials.gov ID
- NCT02499237
- Acronym / sponsor ID
- AfterDmab / AfterDmab
- Conditions
- Postmenopausal Osteoporosis
- Keywords
- osteoporosis, denosumab, zoledronic acid, bone mineral density, bone markers
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- 424 General Military HospitalUniversity, hospital or other
- Collaborators
- 251 Hellenic Air Force & VA General Hospital, Leiden University Medical Center
- Study start
- Jul 2015 (actual)
- Primary completion
- Nov 2018 (actual)
- Study completion
- 26 Nov 2018 (actual)
- First posted
- 16 Jul 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Discontinuation of denosumab results in a rebound rise of bone turnover markers and gradual loss of the achieved bone mineral density gains. In contrast, bisphosphonates, such as zoledronic acid, remain within the skeleton acting for several months or even years after discontinuation while maintaining bone mineral density despite the cessation of treatment. In this study, the investigators aim to evaluate changes in bone mineral density of the lumbar spine and the femoral neck, as well as in bone turnover markers one year after treatment discontinuation both in denosumab-treated women and in denosumab-treated women who switched to zoledronic acid infusion one year before treatment discontinuation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Denosumab | Active comparator | Drug: DenosumabPatients 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 |
| Denosumab plus zoledronic acid | Experimental | Drug: Zoledronic acidPatients 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 |
Who may qualify
- Ages
- 50 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- postmenopausal women
- osteopenic (T-score > -2.5 but < -1.0) after treatment with denosumab
Key exclusion criteria (5 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DenosumabAlso: ProliaTreatment of low bone mass with subcutaneous injections of denosumab 60 mg every 6 months for one year | Drug | Denosumab |
| Zoledronic acidAlso: AclastaTreatment of low bone mass with a single infusion of zoledronic acid 5 mg for one year | Drug | Denosumab plus zoledronic acid |
Primary outcome
bone mineral density of the lumbar spine
Time frame: from 12 to 24 months
differences between the 2 arms in the changes of lumbar spine bone mineral density measured by dual-energy X-ray absorptiometry
5 secondary outcomes
bone mineral density of the femoral neck
Time frame: from 12 to 24 months
C-terminal telopeptide of type I collagen
Time frame: from 12 to 15, 18, 24 months
propeptide of procollagen type I
Time frame: from 12 to 15, 18, 24 months
bone mineral density of the lumbar spine
Time frame: from baseline to 12 months
bone mineral density of the femoral neck
Time frame: from baseline to 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Mar 2019.
- Background: PubMed 18539106Miller 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.
- Background: PubMed 21289258Bone 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.
- Background: PubMed 22571169Black 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.
- Background: PubMed 22571168Whitaker 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.
- Derived from this study: PubMed 33386953Anastasilakis 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Athanasios D Anastasilakis, PhD principal investigator
424 General Military Hospital, Thessaloniki, Greece
Polyzois Makras, PhD principal investigator
251 Airforce and VA General Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Denosumab and Zoledronic acid in people with Postmenopausal Osteoporosis, run by 424 General Military Hospital at 2 sites in Greece.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
bone mineral density of the lumbar spine (time frame: from 12 to 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02499237, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Mar 2019.