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A Clinical Trial to Evaluate Efficacy of Once or Twice ZOledronic Acid After Different Duration of denOsumMab Administration in Postmenopausal Women With Osteoporosis (ZOOM Study)

Primary Purpose

Osteoporosis

Status
Recruiting
Phase
Phase 4
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Zoledronic acid, once
Zoledronic acid, twice
Sponsored by
Yonsei University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Osteoporosis

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  1. Postmenopausal women (defined as no menstruation for more than 48 weeks prior to screening and no other pathological or physiological causes. If in doubt, a serum follicle-stimulating hormone (FSH) test may be performed at screening)
  2. Patients diagnosed with osteoporosis, osteoporotic fractures, received at least two doses of denosumab, and who have osteopenia in follow-up DXA

Exclusion Criteria:

  1. Secondary osteoporosis (Systemic glucocorticoid use, aromatase inhibitor, thyrotoxicosis, hypeparathyroidism, etc)
  2. Active cancer treatment
  3. Inflammatory bowel disease
  4. History of medication related osteonecrosis of jaw(MRONJ)
  5. low-energy fracture within the last 12months
  6. Estimated glomerular filtration rate (eGFR) < 35 mL/min
  7. Hepatic dysfunction (aspartate transaminase (AST)/alanine transferase (ALT) > 3 x upper normal limit)
  8. Contraindication for zoledronic acid according to the SPC
  9. Allergic to zoledronic acid

Sites / Locations

  • Yonsei University Health System, Severance HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Denosumab short-term user

Denosumab long-term user

Arm Description

Denosumab injection less than 5 times

Denosumab injection more than 5 times

Outcomes

Primary Outcome Measures

BMD lumbar spine
Change in lumbar spine BMD from baseline to one year after the zoledronic acid infusion

Secondary Outcome Measures

BMD Femoral neck and total hip
Changes in femoral neck and total hip BMD from baseline to one year after the zoledronic acid infusion
Bone turnover marker
Changes in p-CTX and P1NP From Baseline to Six and twelve months After the Zoledronic Acid Infusion.
Vertebral fracture
Morphometric Vertebral Fractures Assessed by whole spine x-ray

Full Information

First Posted
April 29, 2022
Last Updated
April 29, 2022
Sponsor
Yonsei University
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1. Study Identification

Unique Protocol Identification Number
NCT05361408
Brief Title
A Clinical Trial to Evaluate Efficacy of Once or Twice ZOledronic Acid After Different Duration of denOsumMab Administration in Postmenopausal Women With Osteoporosis (ZOOM Study)
Official Title
A Single Center, Open-label, Parallel, Phase IV Clinical Trial to Evaluate Efficacy of Once or Twice ZOledronic Acid After Different Duration of denOsumMab Administration in Postmenopausal Women With Osteoporosis
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Recruiting
Study Start Date
February 28, 2022 (Actual)
Primary Completion Date
September 2023 (Anticipated)
Study Completion Date
September 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yonsei University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Denosumab(Dmab) is a monoclonal antibody that inhibits the receptor-activator of nuclear factor kappa-B ligand. It improves bone density and reduces fractures by inhibiting osteoclast recruitment and differentiation. Although the FREEDOM trial showed Dmab increase bone mineral density for ten years, the effect was reversible. When Dmab is discontinued, the rebound phenomenon, the bone mineral density returns to the pre-treatment value, and multiple vertebral fractures may occur. Recently, a guideline to administer bisphosphonates sequentially when Dmab is discontinued has been published. In several studies, Zoledronic acid prevented bone loss after denosumab discontinuation with a single administration in Dmab short-term(less than 2.5years) users, but in Dmab long-term(more than 2.5years) users, zoledronic acid did not fully prevent loss of BMD. Our study tried to evaluate that ZOL administration twice for six months apart in long-term Dmab users is not inferior to a single administration of ZOL in Dmab short-term users.
Detailed Description
Background Dmab is an osteoporosis treatment that improves bone density and lowers the risk of fractures. However, in a recent study, it is known that cases in which bone density decreases and multiple vertebral fractures occur when Dmab is discontinued. Therefore, the guideline recommends using zoledronic acid sequentially when discontinuing Dmab. However, the effect of preserving bone mineral density in patients who discontinue Dmab after using a long period is still not known. Aim To investigate the difference in lumbar bone mineral density between the two groups when zoledronic acid was administered differently according to the administration period after discontinuation of denosumab in postmenopausal osteoporosis patients. Methods A prospective, single-center, open-label, parallel, intervention study in 114 patients investigating the difference in bone mineral density between the short-term denosumab group and long-term denosumab group when zoledronic acid was administered differently. Each group is classified into a short-term group when used for less than 2.5 years and a long-term group when used for more than 2.5 years according to the maintenance period of the denosumab. The short-term group administrates zoledronic acid once six months after the last denosumab injection, and the long-term group administrates zoledronic acid six months and 12 months after the last denosumab injection, respectively. In the long-term group, if the side effect is severe after the first zoledronic acid administration and additional administration is difficult, it can be replaced with risedronic acid and maintained for another six months. The patients will be monitored with DXA at baseline and 12 months. Bone turnover marker (b-crosslap(CTx), P1NP) will be monitored at 6 and 12 months after the infusion of the first zoledronic acid. Whole spine x-rays are taken at baseline and 12 months after the zoledronic acid injection to check for vertebral fractures. Perspectives Osteoporosis is a disease that requires continuous management in old age. In order to prevent fractures, the order and maintenance of drug administration should be decided from a long-term perspective. Denosumab is a potent inhibitor of bone resorption which can be used in patients with high risk and very high fracture risk. But since it is reversible, additional treatment must be continued to maintain bone mass when the drug is discontinued. This study will show if two injections of zoledronic acid six months apart in long-term denosumab patients can effectively prevent bone loss compared to a single administration of zoledronic acid in the short-term denosumab group.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoporosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
114 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Denosumab short-term user
Arm Type
Active Comparator
Arm Description
Denosumab injection less than 5 times
Arm Title
Denosumab long-term user
Arm Type
Active Comparator
Arm Description
Denosumab injection more than 5 times
Intervention Type
Drug
Intervention Name(s)
Zoledronic acid, once
Other Intervention Name(s)
Zoledronate
Intervention Description
Intravenous infusion of 5mg zoledronic acid, once
Intervention Type
Drug
Intervention Name(s)
Zoledronic acid, twice
Other Intervention Name(s)
Zoledronate
Intervention Description
Intravenous infusion of 5mg zoledronic acid for 6month interval, twice
Primary Outcome Measure Information:
Title
BMD lumbar spine
Description
Change in lumbar spine BMD from baseline to one year after the zoledronic acid infusion
Time Frame
One year
Secondary Outcome Measure Information:
Title
BMD Femoral neck and total hip
Description
Changes in femoral neck and total hip BMD from baseline to one year after the zoledronic acid infusion
Time Frame
One year
Title
Bone turnover marker
Description
Changes in p-CTX and P1NP From Baseline to Six and twelve months After the Zoledronic Acid Infusion.
Time Frame
One year
Title
Vertebral fracture
Description
Morphometric Vertebral Fractures Assessed by whole spine x-ray
Time Frame
One year

10. Eligibility

Sex
Female
Gender Based
Yes
Gender Eligibility Description
Women
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Postmenopausal women (defined as no menstruation for more than 48 weeks prior to screening and no other pathological or physiological causes. If in doubt, a serum follicle-stimulating hormone (FSH) test may be performed at screening) Patients diagnosed with osteoporosis, osteoporotic fractures, received at least two doses of denosumab, and who have osteopenia in follow-up DXA Exclusion Criteria: Secondary osteoporosis (Systemic glucocorticoid use, aromatase inhibitor, thyrotoxicosis, hypeparathyroidism, etc) Active cancer treatment Inflammatory bowel disease History of medication related osteonecrosis of jaw(MRONJ) low-energy fracture within the last 12months Estimated glomerular filtration rate (eGFR) < 35 mL/min Hepatic dysfunction (aspartate transaminase (AST)/alanine transferase (ALT) > 3 x upper normal limit) Contraindication for zoledronic acid according to the SPC Allergic to zoledronic acid
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yumie Rhee
Phone
82-2-2228-0883
Email
yumie@yuhs.ac
Facility Information:
Facility Name
Yonsei University Health System, Severance Hospital
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yumie Rhee
Phone
82-2-2228-0883
Email
yumie@yuhs.ac

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33103722
Citation
Tsourdi E, Zillikens MC, Meier C, Body JJ, Gonzalez Rodriguez E, Anastasilakis AD, Abrahamsen B, McCloskey E, Hofbauer LC, Guanabens N, Obermayer-Pietsch B, Ralston SH, Eastell R, Pepe J, Palermo A, Langdahl B. Fracture risk and management of discontinuation of denosumab therapy: a systematic review and position statement by ECTS. J Clin Endocrinol Metab. 2020 Oct 26:dgaa756. doi: 10.1210/clinem/dgaa756. Online ahead of print.
Results Reference
background
PubMed Identifier
33813753
Citation
Solling AS, Harslof T, Langdahl B. Treatment With Zoledronate Subsequent to Denosumab in Osteoporosis: A 2-Year Randomized Study. J Bone Miner Res. 2021 Jul;36(7):1245-1254. doi: 10.1002/jbmr.4305. Epub 2021 Apr 20.
Results Reference
background

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A Clinical Trial to Evaluate Efficacy of Once or Twice ZOledronic Acid After Different Duration of denOsumMab Administration in Postmenopausal Women With Osteoporosis (ZOOM Study)

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