Alendronate in an Weekly Effervescent Tablet Formulation Following Denosumab Discontinuation (BAD)

September 28, 2023 updated by: 251 Hellenic Air Force & VA General Hospital

Alendronate in an Weekly Effervescent Tablet Formulation for Preservation of Bone Mass After Denosumab Discontinuation in Postmenopausal Women With Low Bone Mass. An Observational Study (Binosto After Denosumab - The BAD Study)

Discontinuation of denosumab results in a rebound response of bone turnover markers, which rise above baseline at 3 months and remain elevated until reaching again baseline levels approximately 30 months after the last dose. Bone mineral density (BMD) gains are also lost and BMD values reach original baseline values after 1-2 years off-treatment.For the above reasons, current literature recommends that patients who discontinue denosumab should continue to receive either intravenous (iv) or oral (peros) bisphosphonate therapy for some time. The study aims to investigate changes in the BMD of the lumbar spine 12 months after transitioning from denosumab to oral alendronate 70 mg in a weekly effervescent tablet formulation

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Denosumab, a monoclonal antibody against the receptor activator of nuclear factor κ-Β ligand (RANKL), is a potent antiresorptive agent commonly prescribed in patients with postmenopausal osteoporosis. Discontinuation of denosumab results in a rebound response of bone turnover markers, which rise above baseline at 3 months and remain elevated until reaching again baseline levels approximately 30 months after the last dose. Bone mineral density (BMD) gains are also lost and BMD values reach original baseline values after 1-2 years off-treatment, in contrast to bisphosphonates, which remain within the skeleton acting for several months or even years after discontinuation while preserving most of the BMD gains achieved despite the cessation of treatment.

For the above reasons, current literature recommends that patients who discontinue denosumab should continue to receive either intravenous (iv) or oral (peros) bisphosphonate therapy for some time. Due to lack of specifically designed studies, the period of treatment with bisphosphonates after denosumab discontinuation has been arbitrarily proposed to be 1 to 2 years. Preservation of BMD gains after denosumab discontinuation has so far been demonstrated: (a) with one year of alendronate treatment, in a study designed to investigate patients' compliance to treatment, and b) with a single dose of zolendronate 5mg iv in a recent study specifically designed to address this question in which BMD levels remained stable for the next two years.

Preventing bone loss, and the reported high risk of multiple vertebral fractures after discontinuation of denosumab treatment, is a clinical issue of critical importance raising serious concerns to the international scientific community and needs to be addressed. Clinical studies specifically designed to investigate both the efficacy of various bisphosphonates and the optimal duration of their administration in order to avoid the reported adverse effects of denosumab discontinuation are currently lacking.

This study aims to investigate changes in the BMD of the lumbar spine (LS) and femoral neck (FN) 12 months after transitioning from denosumab to oral alendronate 70 mg in a weekly effervescent tablet formulation. Alendronate will be given either for 6 or 12 months following Denosumab discontinuation

Study Type

Observational

Enrollment (Actual)

92

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Polyzois Makras, MD, PhD
  • Phone Number: +306944549654
  • Email: pmakras@gmail.com

Study Contact Backup

Study Locations

  • Greece
    • Attiki
      • Athens, Attiki, Greece, 11525
        • 251 Hellenic Air Force & VA General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 88 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

N/A

Sampling Method

Non-Probability Sample

Study Population

The study will include postmenopausal Caucasian women who were treated with denosumab and became osteopenic (BMD T-score of > -2.5 at the LS and the non-dominant FN) and were assigned from their treating physician to receive treatment with alendronate in an effervescent tablet formulation for either 6 months (Group 6, n=46) and then followed for another 6 months without medication, or 12 months of continuous treatment with alendronate (Group 12, n=46). As this is an observational study, patients could be either referred from their treating physicians or could be actually followed by the investigators themselves in case the investigator is the treating physician

Description

Inclusion Criteria:

i) osteopenic postmenopausal Caucasian women following Dmab treatment ii) assignment to treatment with alendronate in an effervescent tablet formulation following Dmab discontinuation

Exclusion Criteria:

i) secondary osteoporosis; ii) diseases that could affect bone metabolism iii) medications that could affect bone metabolism iv) chronic kidney disease (stage >3b) and/or liver failure v) neoplastic disease vi) hypersensitivity to alendronate or to any of the excipients vii) abnormalities of the esophagus and other factors which delay esophageal emptying such as stricture or achalasia viii) inability to stand or sit upright for at least 30 minutes ix) hypocalcaemia x) confirmed esophagitis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Group Alendronate 6m
Postmenopausal Caucasian women who were treated with denosumab and became osteopenic (BMD T-score of > -2.5 at the LS and the non-dominant FN) and were assigned from their treating physician to receive treatment with alendronate in an effervescent tablet formulation for 6 months and then followed for another 6 months without medication. In case serum P1NP levels are > 35μg/L and/or serum CTX levels are > 280 ng/L at 9 months (3 months following alendronate discontinuation) the patients would be strongly advised to restart alendronate treatment.
Drug: Binosto 70Mg Effervescent Tablet
As discussed in group descriptions
Other Names:
  • calcium carbonate 1000 mg/d and cholecalciferol 800 IU/d
Group Alendronate 12m
Postmenopausal Caucasian women who were treated with denosumab and became osteopenic (BMD T-score of > -2.5 at the LS and the non-dominant FN) and were assigned from their treating physician to receive treatment with alendronate in an effervescent tablet formulation for 12 months.
Drug: Binosto 70Mg Effervescent Tablet
As discussed in group descriptions
Other Names:
  • calcium carbonate 1000 mg/d and cholecalciferol 800 IU/d

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bone Mineral Density LS
Time Frame: 12 months
Changes in the BMD of the lumbar spine 12 months after transitioning from denosumab to oral alendronate 70 mg in a weekly effervescent tablet formulation.
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bone Mineral Density FN
Time Frame: 12 months
Changes in the BMD of the femoral neck (FN) of the non-dominant hip 12 months after transitioning from denosumab to oral alendronate 70 mg in a weekly effervescent tablet formulation
12 months
Serum levels of bone turnover markers (BTMs): P1NP, CTX and TRAP5b
Time Frame: 12 months
Changes in BTMs 12 months after transitioning from denosumab to oral alendronate 70mg in a weekly effervescent tablet formulation.
12 months
Comparison of Bone Mineral Density LS
Time Frame: 12 months
Comparison of changes in the BMD of the LS after transitioning from denosumab to 12 months versus 6 months of treatment with oral alendronate 70 mg in a weekly effervescent tablet formulation.
12 months
Comparison of Bone Mineral Density FN
Time Frame: 12 months
Comparison of changes in the BMD of the FN of the non-dominant hip after transitioning from denosumab to 12 months versus 6 months of treatment with oral alendronate 70mg in a weekly effervescent tablet formulation.
12 months
Comparison of changes in: the serum levels of bone turnover markers (BTMs) P1NP, CTX and TRAP5b; the 24-hours urine levels of calcium
Time Frame: 12 months
Comparison of changes in the levels of serum BTMs and 24hours urine calcium after 12 months versus 6 months treatment with oral alendronate 70mg in a weekly effervescent tablet formulation in patients previously treated with denosumab
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

251 Hellenic Air Force & VA General Hospital

Collaborators

Laikο General Hospital, Athens
424 General Military Hospital

Investigators

  • Study Chair: Maria Yavropoulou, MD, PhD, LAIKO General Hospital, Athens, Greece
  • Principal Investigator: Polyzois Makras, MD, PhD, 251 Hellenic Airforce Gen. Hospital, Athens, Greece
  • Study Director: Athanasios D Anastasilakis, MD, PhD, 424 Gen. Military Hospital Thessaloniki, Greece

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2020

Primary Completion (Estimated)

September 25, 2024

Study Completion (Estimated)

November 1, 2024

Study Registration Dates

First Submitted

April 4, 2020

First Submitted That Met QC Criteria

April 4, 2020

First Posted (Actual)

April 8, 2020

Study Record Updates

Last Update Posted (Actual)

September 29, 2023

Last Update Submitted That Met QC Criteria

September 28, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • F076/AD1704/S606/18-2-2020
  • 2550/14-2-20 (Other Identifier: LAIKO Hospital)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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