Antibiotic treatment In patients with chronic low back pain and Modic changes (the AIM study): study protocol for a randomised controlled trial

Kjersti Storheim,Lars Grøvle,Jörg Aßmus,Sigrun Randen,Nils Vetti,Jan Sture Skouen,Margreth Grotle,Olav Lutro,Øystein P Nygaard ,Ansgar Espeland,Gunn Hege Marchand,Thomas Kadar,Anne Julsrud Haugen,Elina Iordanova Schistad ,Terese Fors,Jens Ivar Brox,Anne Froholdt,Linda M Pedersen,Audny Anke,John‐Anker Zwart

doi:10.1186/s13063-017-2306-8

Abstract

BackgroundA previous randomised controlled trial (RCT) of patients with chronic low back pain (LBP) and vertebral bone marrow (Modic) changes (MCs) on magnetic resonance imaging (MRI), reported that a 3-month, high-dose course of antibiotics had a better effect than placebo at 12 months’ follow-up. The present study examines the effects of antibiotic treatment in chronic LBP patients with MCs at the level of a lumbar disc herniation, similar to the previous study. It also aims to assess the cost-effectiveness of the treatment, refine the MRI assessment of MCs, and further evaluate the impact of the treatment and the pathogenesis of MCs by studying genetic variability and the gene and protein expression of inflammatory biomarkers.Methods/designA double-blinded RCT is conducted at six hospitals in Norway, comparing orally administered amoxicillin 750 mg, or placebo three times a day, over a period of 100 days in patients with chronic LBP and type I or II MCs at the level of a MRI-confirmed lumbar disc herniation within the preceding 2 years. The inclusion will be stopped when at least 80 patients are included in each of the two MC type groups. In each MC type group, the study is designed to detect (β = 0.1, α = 0.05) a mean difference of 4 (standard deviation 5) in the Roland Morris Disability Questionnaire score between the two treatment groups (amoxicillin or placebo) at 1-year follow-up. The study includes cost-effectiveness measures. Blood samples are assessed for security measures and for possible inflammatory mediators and biomarkers at different time points. MCs are evaluated on MRI at baseline and after 12 months. A blinded intention-to-treat analysis of treatment effects will be performed in the total sample and in each MC type group.DiscussionTo ensure the appropriate use of antibiotic treatment, its effect in chronic LBP patients with MCs should be re-assessed. This study will investigate the effects and cost-effectiveness of amoxicillin in patients with chronic LBP and MCs at the level of a disc herniation. The study may also help to refine imaging and characterise the biomarkers of MCs.Trial registrationClinicalTrials.gov, ID: NCT02323412. Registered on 21 November 2014.

Highlights

A previous randomised controlled trial (RCT) of patients with chronic low back pain (LBP) and vertebral bone marrow (Modic) changes (MCs) on magnetic resonance imaging (MRI), reported that a 3-month, high-dose course of antibiotics had a better effect than placebo at 12 months’ follow-up
Secondary ITT analyses of treatment effect are (1) linear mixed-effects models (LME) for repeated measures of Roland and Morris Disability Questionnaire (RMDQ) and LBP intensity and (2) responder analyses, comparing proportions of patients with > 75%, > 50% and > 30% reduction in RMDQ score from baseline to 1-year follow-up between treatment groups and reporting number needed to treat (NNT) with 95% confidence intervals (CIs)
This article presents the design and rationale for a doubleblind RCT comparing the effect of amoxicillin and placebo for patients with chronic LBP and Modic change (MC) type I or II at the level of a previously herniated disc

Summary

Introduction

A previous randomised controlled trial (RCT) of patients with chronic low back pain (LBP) and vertebral bone marrow (Modic) changes (MCs) on magnetic resonance imaging (MRI), reported that a 3-month, high-dose course of antibiotics had a better effect than placebo at 12 months’ follow-up. One study assessed antibiotic treatment as a new treatment for selected patients with persistent LBP and type I MCs at the level of a previously herniated intervertebral disc [18]. They hypothesised that a lowgrade infection of the disc by the anaerobic Proprionibacterium acnes bacteria (P. acnes) resulted in adjacent bone oedema (type I MCs) and chronic disabling LBP. In a randomised controlled trial (RCT), 100 days of antibiotic treatment with amoxicillin clavulanate tablets was more effective than placebo in all primary and secondary outcomes at 12 months’ follow-up [18]

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