Randomized, Placebo-Controlled Trial Assessing Amoxicillin Efficacy in Chronic Non-Specific Low Back Pain with Modic Type I Changes

The primary objective of this study is to evaluate the **efficacy** of a three-month antibiotic treatment with amoxicillin compared to a placebo in patients suffering from chronic low back pain (LBP) with Modic type I changes as observed on MRI. This is clinically relevant as chronic LBP is a prevalent condition that significantly impacts quality of life and healthcare resources, and Modic type I changes are associated with inflammation and pain. Identifying effective treatments could lead to improved patient outcomes and reduced healthcare costs.

Secondary objectives include assessing the cost-effectiveness of the three-month antibiotic treatment with amoxicillin compared to placebo for the same patient group. This evaluation is crucial for determining the economic viability of implementing such a treatment on a larger scale, considering the potential benefits in terms of pain reduction and improved functionality against the costs involved.

The clinical trial focuses on individuals diagnosed with **non-specific low back pain**. The study population includes both male and female participants aged between 18 and 65 years. Participants are required to have chronic low back pain persisting for more than six months following a previously confirmed disc herniation, with Modic Type I changes visible on MRI scans. The trial does not involve a vulnerable population. Participants were selected based on specific criteria, including a mean pain intensity of at least 5 points on a 0-10 NRS scale and affirmative responses to questions regarding pain exacerbation due to training or exercise, sleep disturbances, and morning pain. The sponsor has not provided information regarding the total number of participants. Lifestyle factors such as diet and physical activity were not specified as part of the selection criteria.

The clinical trial is designed to evaluate the **efficacy** of a three-month antibiotic treatment with **amoxicillin** compared to a placebo in patients with chronic low back pain and Modic type I changes as observed on MRI. This study is structured as a randomized, double-blind, placebo-controlled trial, ensuring that neither the participants nor the investigators are aware of the treatment assignments, thus minimizing bias. The trial is classified as low-risk due to the well-known safety profile of amoxicillin, with common adverse reactions being diarrhea, nausea, and skin rash, which are manageable symptomatically.

The trial is expected to commence recruitment on September 2, 2024, and conclude by May 3, 2027. Participants will be involved in the study for a maximum of three months, corresponding to the treatment duration. The study will include several key visits: an initial screening visit to confirm eligibility based on criteria such as age (18-65 years), chronic low back pain duration, and specific MRI findings. Follow-up visits will be scheduled to monitor treatment adherence, collect data on primary and secondary endpoints, and assess any adverse events. The primary endpoint is the measurement of pain and disability using the Roland Morris Disability Questionnaire. Secondary endpoints include assessments of low back pain intensity, leg pain intensity, global perceived effect, health-related quality of life, and other relevant health metrics.

Participants may be withdrawn from the study if they experience significant adverse effects, fail to comply with the study protocol, or choose to withdraw consent. The study's design and procedures are meticulously planned to ensure the collection of high-quality data while safeguarding participant safety and well-being throughout the trial duration.

The clinical trial involves the administration of **Amoxicillin**, a well-established antibiotic, in the form of 500 mg film-coated tablets. The active substance, **amoxicillin**, is of chemical origin and is classified under the ATC code J01CA04. The tablets are manufactured by Brown & Burk UK Limited. Participants in the trial will receive a maximum daily dose of 1000 mg, administered orally. The treatment period is set for a maximum of three months. The pharmaceutical form of the medication ensures ease of administration and compliance monitoring will be conducted to ensure adherence to the dosing schedule.

The study also includes a **placebo** group, which will receive placebo amoxicillin capsules, each containing 500 mg. The placebo is designed to match the experimental medication in appearance to maintain blinding in the trial. The placebo capsules do not contain any active substance and are used to assess the efficacy of the amoxicillin treatment by providing a comparator group. The administration route and frequency for the placebo group will mirror that of the amoxicillin group to ensure consistency in the trial protocol.

The efficacy of the antibiotic treatment in this clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint is the measurement of pain and disability using the Roland Morris Disability Questionnaire (RMDQ). Secondary endpoints include assessments of low back pain (LBP) intensity and leg pain intensity on a 0-10 Numeric Rating Scale (NRS), global perceived effect on a 7-point Likert scale, and health-related quality of life using PROMIS-GH-10 and EQ-5D-5L. Additional secondary endpoints involve self-reported days of sick leave, co-interventions, patient satisfaction with treatment, success of blinding, compliance through pill count, pain self-efficacy via the Pain Self-Efficacy Questionnaire, sleep quality using the Pittsburgh Sleep Quality Index, neuropathic pain assessed by PainDETECT, and MRI imaging at 12 months follow-up to evaluate the outcome of the antibiotic treatment on Modic changes. LBP-related healthcare costs will be measured with cost questionnaires (iMCQ and iPCQ).

The trial is designed as a double-blind randomized placebo-controlled study, with the main objective to assess the efficacy of a three-month antibiotic treatment with **amoxicillin** compared to placebo in patients with chronic low back pain and Modic type I changes on MRI. The trial will include participants aged 18-65 years with chronic low back pain lasting more than six months, following a previous MRI-confirmed disc herniation. The mean pain intensity should be at least 5 points on a 0-10 NRS scale. The study is classified as low risk, considering the well-known profile of amoxicillin and its commonly reported adverse reactions, which are manageable.