Efficacy and Safety of Zoledronic Acid Versus Sodium Chloride in Patients with Chronic Low Back Pain and Modic Changes: A Randomized, Double-Blind, Placebo-Controlled Trial

The primary objective of the ZAMBA trial is to evaluate the **efficacy** and safety of two infusions of 5 mg **zoledronic acid** compared to placebo (NaCl) in reducing back-specific disability in patients with chronic low back pain associated with Modic changes. This is measured using the Oswestry Disability Index (ODI), a clinically relevant tool for assessing the degree of disability and functional impairment in individuals with back pain. The trial aims to determine whether zoledronic acid can provide a significant therapeutic benefit over placebo, potentially offering a new treatment option for this patient population.

Secondary objectives include improving MRI assessment of Modic changes, conducting health economic analyses, and assessing underlying biological mechanisms and biomarkers. These objectives aim to enhance the understanding of Modic changes and their impact on low back pain, as well as to evaluate the cost-effectiveness and biological basis of the treatment.

The clinical trial involves participants diagnosed with **chronic low back pain** characterized by Modic changes. The study population includes both male and female subjects, with an age range corresponding to adults. The trial does not involve a vulnerable population. The sponsor has not provided the total number of participants. Participants were selected based on specific criteria, including experiencing low back pain for more than 50% of days over a duration exceeding six months, with an Oswestry Disability Index score of 30 or higher, and/or a Numerical Rating Scale pain intensity score of 5 or higher. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The selection criteria ensure that participants have a significant level of disability and pain, which is essential for assessing the efficacy and safety of the treatment under investigation.

The clinical trial is designed to evaluate the efficacy and safety of **zoledronic acid** in patients with chronic low back pain associated with Modic changes. This is a randomized, double-blind, placebo-controlled, multicenter trial. Participants will be randomly assigned to receive either two infusions of 5 mg zoledronic acid or a placebo (NaCl 0.9% solution) over a 12-month period. The primary endpoint is the change from baseline in the mean Oswestry Disability Index (ODI) score at one year. Secondary endpoints include changes in low back pain intensity, Roland Morris Disability Questionnaire score, EQ-5D, and global perceived effect at one year, as well as the use of concomitant treatments.

The trial will commence with a screening visit to confirm eligibility based on criteria such as low back pain for more than 50% of days over six months, an ODI score of ≥30, and specific Modic changes. Following successful screening, participants will be enrolled and randomized. Study visits will occur at baseline, followed by regular follow-up visits to monitor safety and efficacy outcomes. The end-of-study visit will occur at the conclusion of the 12-month treatment period.

Participant involvement is expected to last approximately 12 months, with conditions for early termination including adverse events, withdrawal of consent, or protocol non-compliance. The trial is anticipated to start recruitment on June 1, 2025, and is estimated to conclude by January 15, 2029. The trial is not classified as low intervention and is categorized as a therapeutic confirmatory clinical trial.

The clinical trial involves the administration of **Aclasta 5 mg solution for infusion**, which contains the active substance **zoledronic acid**. This experimental medication is provided in the form of a solution for infusion and is administered intravenously. The dosage is set at 5 mg per infusion, with a maximum total dose of 10 mg over the course of the treatment. The treatment period is limited to 12 months. Zoledronic acid is a chemical compound classified under the ATC code M05BA08, and it is manufactured by Sandoz Pharmaceuticals D.D. The administration schedule involves two infusions, and participant compliance is monitored throughout the trial to ensure adherence to the dosing regimen.

In addition to the experimental treatment, the study utilizes **NaCl 0.9% B. Braun, solution pour perfusion** as a placebo comparator. This non-experimental treatment contains **sodium chloride** as the active substance and is also provided in the form of a solution for injection/infusion. The placebo is administered via infusion, with a maximum daily dose of 100 ml and a total maximum dose of 200 ml over the treatment period. The placebo is manufactured by B. Braun Melsungen AG and is classified under the ATC code B05BB01. The administration of the placebo follows the same schedule as the experimental treatment, ensuring a double-blind study design. Compliance with the placebo administration is similarly monitored to maintain the integrity of the trial results.

The efficacy of the clinical trial titled "ZAMBA: Zoledronic Acid for Modic Back Pain" will be assessed by evaluating the reduction in back-specific disability in patients with chronic low back pain with Modic changes. The primary endpoint for efficacy assessment is the change from baseline at one year in the mean Oswestry Disability Index (ODI) score. This index is a validated scale used to measure the degree of disability and functional impairment due to back pain.

Secondary endpoints include changes from baseline at one year in mean low back pain (LBP) intensity, as measured by three Numerical Rating Scale (NRS) scores, changes in the Roland Morris Disability Questionnaire (RMDQ) score, and changes in the EQ-5D score. Additionally, the trial will assess concomitant treatments used between baseline and one-year follow-up, as well as the global perceived effect at one year follow-up. These parameters will be collected and analyzed to provide a comprehensive evaluation of the treatment's efficacy.