Assessment of Efficacy of Zoledronic Acid in the Treatment of Bone Marrow Edema Syndrome (ZoMARS)

August 9, 2024 updated by: Dr. Lothar Seefried, Wuerzburg University Hospital

A Prospective, Bi-centric,Randomized, Primary Double-blind, Placebo-controlled Phase III Study to Assess the Efficacy of Zoledronic Acid in the Treatment of Bone Marrow Edema Syndrome

The primary aim is to test the reduction of bone marrow edema syndrome after a singular intravenous treatment with Zoledronic Acid within 6 weeks compared to placebo. The volume of the edema is defined as biometric data measured by the use of MRT before and six weeks after treatment. The hypothesis has to be checked whether Zoledronic Acid is efficient in the treatment of painful bone marrow edema. A statistically significant reduction of the edema in the MRT is considered as evidence for efficacy.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
48

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

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

Study Locations

  • Germany
    • Bavaria
      • Wuerzburg, Bavaria, Germany, 97074
        • Orthopedic Center for Musculoskeletal Research, Orthopedic Department, University of Wuerzburg
      • Wuerzburg, Bavaria, Germany, 97080
        • Department of trauma, hand, reconstructive and plastic, University of Wuerzburg

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Men: age over ≥ 18 years or women: age over ≥ 18 years with finished reproductivity according to the following definition:
  • ≥ 12 month persistent natural (spontaneous) amenorrhoea (women aged <50: additionally: FSH >40MIE/ml and estrogen deficiency of <30pg/ml or a negative estrogen test)
  • status post hysterectomy and / or bilateral oophorectomy
  • finished reproduction planning
  • secure diagnosis of bone marrow edema using MRT
  • current osteologic basic laboratory values (≤ 4 weeks before V2) according to DVO criteria
  • presence of an personally signed informed consent for the participation in the study

Exclusion Criteria:

  • - subchondral bone loss or already occurred cartilage damage due to the bone marrow edema
  • reactive bone marrow edema with advanced arthrotic changes in the adjacent joint (grade III and IV according to Kellgren and Lawrence)
  • patients with edematous changes in bone marrow due to the diagnosis of M. Sudeck / algodystrophy / Complex Regional Pain Syndrome (CRPS)
  • patients with known hypo- and hyperparathyroidism, osteogenesis imperfecta, osteomalacia, M. Paget or another systemic skeletal diseases, except osteoporosis
  • patients with bone necrosis in the painful skeletal region
  • patients with infectious process at the affected bone or the adjacent joint and adjacent soft parts, respectively
  • patients with diagnosed or assumed rheumatoid arthritis, Lupus erythematodes, collagenosis or vasculitides

  • patients with advanced renal insufficiency (GFR according to Cockcroft

    / Gault ≤ 40 ml/min/KO)

  • patients with malignant diseases with osseous manifestation in anamnesis/history
  • status post malignant basic/primary disease with large dosed chemotherapy
  • current or massive dose therapy completed before less than 6 weeks (>7.5mg prednisolon equivalent) with glucocorticoids
  • patients with a malignant tumor disease within the past 5 years, independent from the affected organ system and independent from the implemented treatment, the presence of a relapse or metastatic invasion, except basal cell carcinoma and squamous-cell carcinoma of the skin Current treatment due to uveitis
  • vague/ambiguous hyper- or hypocalcemia, hyper- or hypophosphatemia
  • etiological vague/ambiguous AP-increase
  • symptomatic renal calculus or nephrocalcinosis within 2 years before V2
  • recent fracture within the last 3 months independent of the localisation
  • non consolidated fractures
  • previous treatment with i.v. bisphosphonates within the last 12 months
  • previous treatment with oral bisphosphonates within the last 12 months and longer than 3 months
  • pre-treatment with prostacyclin analogs (Ilomedin® / Iloprost®) within the past 6 months
  • Current treatment due to inflammatory diseases of the jaw area as well as planned tooth extractions or tooth extractions less than 6 months ago or oral surgery implant treatment
  • pregnancy or nursing period
  • patients immediately involved in the conduction of the trial and relatives
  • patients with current proceedings related to the bone marrow edema
  • patients for which the participation in the study carries an increased risk under consideration of the health condition due to the assessment of the investigator
  • participation in another clinical trial within 30 days before study start or during the trial
  • participation of patient who might be dependent on the investigator, also the spouse, parents or children

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

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: NaCl Solution
Drug: Placebo
NaCl Solution
Active Comparator: Aclasta
Drug: Aclasta
1 x intravenous non-current drip (infusion)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Reduction of the Edema Area
Time Frame: Week 6 after administration of a single intravenous dose of zoledronic acid (5 mg)
The volume of the edema in cm³ is defined as biometric data measured by the use of MRI before and six weeks after treatment. Edema volume at screening was set to 100%. Edema volume six weeks after study drug administration was provdied as percentage reduction compared to the value at screening
Week 6 after administration of a single intravenous dose of zoledronic acid (5 mg)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Reduction of Pain (VAS)
Time Frame: Assessment at week 3
Reduction of pain as measured by a Visual Analog Scale (VAS). Range 0-100 with higher values indicating worse pain.
Assessment at week 3
Reduction of Pain
Time Frame: Assessment at week 6
Reduction of pain as measured by a visual analog scale (VAS). Range 0-100. Higher values indicating worse pain.
Assessment at week 6
Quality of Life (Qualeffo-41 Questionnaire)
Time Frame: Assessment at week 3
Quality of life as measured by the Qualeffo-41 questionnaire - a quality of life questionnaire in patients with fractures of the European Foundation for Osteoporosis Higher values indicate worse quality of life
Assessment at week 3
Quality of Life (Qualeffo-41 Questionnaire)
Time Frame: Assessment at week 6
Quality of life as measured by the Qualeffo-41 questionnaire - a quality of life questionnaire in patients with vertebral fractures of the European Foundation for Osteoporosis
Assessment at week 6
Subjective Estimation of Medical Condition (PDI)
Time Frame: Assessment at week 3
Subjective estimation of medical condition as assessed by PDI (Pain Disability Index). Range 0-70. The higher the index the greater the person's disability due to pain.
Assessment at week 3
Subjective Estimation of Medical Condition (PDI)
Time Frame: Assessment at week 6
Subjective estimation of medical condition as assessed by PDI (Pain Disability Index)
Assessment at week 6
Number of Additional Medicinal Visits
Time Frame: Assessment at week 3
Number of additional medicinal visits until week 3
Assessment at week 3
Number of Additional Medicinal Visits
Time Frame: Assessment at week 6
Aggregated number of unscheduled medicinal visits
Assessment at week 6
Number of Days of Illness
Time Frame: Assessment at week 6
Aggregated number of days of illness i.e. sick leave from work, assessed until week 6
Assessment at week 6
Number of Days of Illness
Time Frame: Assessment at week 6
Number of days of illness assessed until week 6
Assessment at week 6
Number of Aseptic Bone Necrosis and Fatigue Fractures
Time Frame: Baseline until end of study (week 12)
Assessment of number of patients withaseptic bone necrosis and/or fatigue fractures.
Baseline until end of study (week 12)
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Time Frame: Week 3, 6
including changes in the following parameters according to DVO guidelines: Calcium, Phosphate, Creatinin-Clearance (Cockcroft-Gault), Alkaline Phosphatase, γGT, CRP
Week 3, 6

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Wuerzburg University Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of Wuerzburg
Crolll Gmbh

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Rainer Meffert, Prof. Dr., Department of trauma, hand, reconstructive and plastic, University of Wuerzburg

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 26, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 26, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 2, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 4, 2011

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 5, 2011

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 13, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 9, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CZOL446HDE38T

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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