Chronic Low Back Pain (CLBP), Modic Changes, MSK Conditions
Conditions
Keywords
Antibiotics, Amoxicillin, Low back pain (LBP), Modic changes, Randomized controlled trial
Brief summary
The goal of this clinical trial is to learn if antibiotics (amoxicillin) work to treat chronic low back pain in adults. In some patients, this type of back pain may be caused by bacteria in the vertebrae, resulting in a condition known as "Modic type I change." The main questions the trial aims to answer are: * What is the efficacy (primary objective) of antibiotic treatment for patients with chronic low back pain and Modic type I changes? * What is the cost-effectiveness (secondary objective) of antibiotic treatment for patients with chronic low back pain and Modic type I changes? Researchers will compare amoxicillin to a placebo (a look-alike substance that contains no active drug) to see if amoxicillin works to treat chronic low back pain. Participants in the trial will: * Be invited for an MRI scan to determine if they have a Modic type I change; those who do will be included in the study. * Take either amoxicillin or a placebo daily for 100 days. * Take probiotics daily for 100 days to reduce the occurrence and impact of any side effects from the antibiotics. * Attend clinic visits at baseline (the start), 4 weeks, 3 months, and 12 months for checkups and tests. * Complete questionnaires at baseline, 3 months, 6 months, and 12 months.
Interventions
DRUGAmoxicillin
Antibiotic treatment (amoxicillin) with a dosage of 1000 mg (3 times a day) for a period of 100 days
OTHERPlacebo
Placebo with a dose of 1000 mg (3 times a day) for a period of 100 days
Sponsors
Bart Koes
Erasmus University Rotterdam
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Aged 18-65 years. * Chronic low back pain (i.e. duration \>6 months) after a previous (MRI confirmed) disc herniation within the past 6 months to 2 years. * At least 2 of the following questions should be answered with "Yes": * Does training and/or exercise increase your pain? * Is your sleep during the night disturbed due to your back pain? * Is it painful to turn over in bed at night? * Do you suffer from morning pain? * The mean pain intensity should be at least 5 points on a 0-10 NRS-scale, calculated as the mean pain intensity of 3 indices: current pain, worst pain within the preceding two weeks, and the usual mean pain within the preceding two weeks. * Modic Type I changes visible on the MRI-scan in the vertebrae adjacent to the previous herniated disc.
Exclusion criteria
* Received antibiotic treatment in the past month. * Current pregnancy, lactation or pregnancy-wish. * Severe physical or psychiatric co-morbidities. * LBP resulting from a specific cause such as a tumor or fracture. * Surgery or epidural injection in the past 6 months. * Previous antibiotic course of 100 days. * Contra-indication for amoxicillin use: allergy to penicillins/amoxicillin, cephalosporin or carbapenem; mononucleosis; leukemia; phenylketonuria (PKU) * Contra-indication for MRI. * Current use of any of the following medications: allopurinol, methotrexate, phenylbutazone or probenecid. * Hepatic or renal (eGFR≤30) impairment. * Inability to swallow capsules.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Roland Morris Disability Questionnaire (RMDQ) | The measurements are scheduled at baseline and at 3, 6 and 12 months follow-up. | The primary outcome is pain and disability measured with the Roland Morris Disability Questionnaire (RMDQ). The scale ranges from 0-24 in which a higher score indicates higher disability. The RMDQ was also the primary outcome in the previous trials, and it is a recommended core outcome measure for trials in LBP. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| LBP-intensity (0-10 NRS-scale) | Measured at baseline, 3 months, 6 months and 12 months | In the form of a questionnaire |
| Leg pain intensity (0-10 NRS-scale) | Measured at baseline, 3 months, 6 months and 12 months | In the form of a questionnaire |
| Health-related quality of life (PROMIS-GH-10) | Measured at baseline, 3 months, 6 months and 12 months | In the form of a questionnaire |
| Health-related quality of life (EQ-5D-5L) | Measured at baseline, 3 months, 6 months and 12 months | In the form of a questionnaire |
| Self-reported number of days with sick leave | Measured at baseline, 3 months, 6 months and 12 months | In the form of a questionnaire |
| Co-interventions (pharmacological and non-pharmacological) | Measured at baseline, 3 months and 12 months | In the form of a questionnaire |
| Global perceived effect (7-point Likert scale) | Measured at 3 months, 6 months and 12 months | In the form of a questionnaire |
| Patients' satisfaction with treatment (7-point Likert scale) | Measured at baseline, 3 months and 12 months | In the form of a questionnaire |
| Success of blinding | Measured at 3 months and 12 months | In the form of a questionnaire |
| Compliance | Measured at 3 months | A pill count will be conducted |
| Pain self-efficacy (Pain Self-Efficacy Questionnaire) | Measured at baseline, 3 months, 6 months and 12 months | In the form of a questionnaire |
| Sleep questionnaire (Pittsburgh Sleep Quality Index) | Measured at baseline, 3 months, 6 months and 12 months | In the form of a questionnaire |
| Neuropathic pain (PainDETECT) | Measured at baseline, 3 months, 6 months and 12 months | In the form of a questionnaire |
| Cost questionnaires (Medical Consumption Questionnaire) | Measured at 3 months, 6 months and 12 months | In the form of a questionnaire |
| Cost questionnaires (Productivity Cost Questionnaire) | Measured at 3 months, 6 months and 12 months | In the form of a questionnaire |
| Gut microbiome composition | Measured at baseline, 3 months, and 12 months | The possible collateral impact of antibiotics on the microbiome would be investigated by comparing the abundance and diversity of microbial and resistome composition between patients in amoxicillin and placebo groups. They would be characterized using whole shotgun and functional metagenomic sequencing data (Dhariwal et al. Gut Microbes, 2023). In short, stools of the patients will be collected at baseline, 3 months, and 12 months. From these samples, the microbial DNA will be extracted using a commercial kit. Libraries for shotgun metagenomic sequencing would be prepared using Ilumina sequencing platform. Low quality and adapter sequences from paired-end reads will be filtered, and human DNA contaminant sequences will be discarded. The high-quality reads will be subjected to taxonomic classification. CARD antimicrobial resistance database will be used to annotate metagenomic reads. |
Countries
Netherlands
Outcome results
None listed