Efficacy of Antibiotic Treatment for Patients with Chronic Low Back Pain and Modic Type I Changes - Randomized Placebo-controlled Trial

Phase 3

Recruiting

• Conditions: MSK Conditions; Chronic Low Back Pain (CLBP); Modic Changes
• Interventions: Drug: Amoxicillin; Other: Placebo

• Registration Number: NCT06771492
• Lead Sponsor: Bart Koes

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-11-21
• Status Verified: 2024-12
• Study First Submitted QC: 2025-01-10
• Last Update Submitted: 2025-01-10
• Study First Posted: 2025-01-13
• Last Update Posted: 2025-01-13
• Study Start: 2025-02
• Primary Completion: 2027-08
• Study Completion: 2027-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 204

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Antibiotic treatment (amoxicillin)	Amoxicillin	A dose of 1000 mg (3 times a day) for a period of 100 days
Placebo	Placebo	A dose of 1000 mg (3 times a day) for a period of 100 days

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

Erasmus Medical Center; 🇳🇱 Rotterdam, Zuid-Holland, Netherlands