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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Bone Marrow Edema

Intervention / Treatment
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* Drug: Aclasta
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Aclasta<br> | Drug: Aclasta<br>* 1 x intravenous non-current drip (infusion)<br>|
| Placebo Comparator: NaCl Solution<br> | Drug: Placebo<br>* NaCl Solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of the Edema area |  | Week 6 after study start | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of pain (VAS) |  | Week 0, 3, 6 | 
| Quality of life (Qualeffo-41 questionnaire - Quality of life questionnaire of the European Foundation for Osteoporosis) |  | Week 0, 3, 6 | 
| Subjective estimation of medical condition (PDI) |  | Week 0, 3, 6 | 
| Number of additional medicinal visits |  | Week 3, 6 | 
| Number of days of illness |  | Week 3, 6 | 
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability | including changes in the following parameters according to DVO guidelines: Calcium, Phosphate, Creatinin-Clearance (Cockcroft-Gault), Alkaline Phosphatase, γGT, CRP | Week 3, 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bone marrow edema, Aclasta