Antibiotics In Modic Changes

NCT02323412 | Completed Phase 3 DMC

• 1 other identifier: 2014/12701
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

Low-back pain (LBP) is the single leading cause for disability worldwide, affects all age groups and has increased from 58 million years lived with disability (YLDs) in 1990 to 83 million YLDs in 2010. The burden is accordingly substantially higher than previously assessed, causing activity limitation and work absence with subsequently enormous economic burden. Norwegian expenses reach at least NOK 24 billions annually whereof a substantial part is hospital costs. The research project responds to this challenge and aim to conduct a multicenter randomized placebo-controlled trial, complemented by a study of epigenetic and molecular biomarkers, to re-examine the finding of a recent randomized controlled trial that antibiotic treatment can cure patients with chronic low back pain (LBP), a former disc herniation and present Modic Changes (MCs). The hypothesis is that MCs is caused by low virulent anaerobic organisms in the disc. Investigators also want to add important new knowledge to the research field beyond the only former RCT by broadening the inclusion criteria to include both patients with type I and type II MCs, improving the MRI assessment of MCs, further clarifying the pathogenesis of MCs by studying genetic variability, gene and protein expression of inflammatory biomarkers, and conducting health economic analysis.

Conditions

Low Back Pain; Modic Changes Type I or II Seen on MRI

Keywords

Low back pain; Chronic; Modic Changes; MRI; epigenetics; antibiotics; randomized placebo controlled trial

Outcome Measures

Primary Outcomes (1)

• Roland Morris Disability Questionnaire

  Self-reported disease-specific disability evaluated by the Roland Morris Disability Questionnaire (RMDQ, scale 0-24, Norwegian translation) from baseline to one year (12 months) follow-up in patients with chronic LBP and MCs type I or II adjacent to a previously herniated disc. The effect will be evaluated in the whole sample (hypothesis A) and in MC type I and II sub-groups (hypothesis B and C). RMDQ will also be evaluated from baseline to post-treatment and used in health economic analysis and in relation to MRI. Primary endpoint of the study is change in RMDQ from baseline to one year (12 months) after start of intervention.

  Evaluated at baseline, post-treatment (100 days after start of intervention), 6, 9 and 12 months after start of treatment.

Secondary Outcomes (10)

• Oswestry Disability Index

  Evaluated at baseline, post-treatment (100 days after start of intervention), and 12 months after start of treatment.

• Lumbar pain: Numeric Rating Scale

  Evaluated at baseline, post-treatment (100 days after start of intervention), 6, 9 and 12 months after start of treatment, and weekly during the treatment period.

• Health-related quality of life: EuroQoL-5D-5L

  Evaluated at baseline, post-treatment (100 days after start of intervention), and 12 months after start of treatment.

• STIR signal on MRI

  Evaluated 6-2 weeks before start of intervention and 12-13 months after start of treatment.

• Leg pain: Numeric Rating Scale

  Evaluated at baseline, post-treatment (100 days after start of intervention), and 12 months after start of treatment.

Other Outcomes (5)

• Symptom-specific well-being

  Evaluated at baseline, post-treatment (100 days after start of intervention), and 12 months after start of treatment.

• Work status

  Evaluated monthly during the whole 12-months study period.

• Co-interventions

  Evaluated monthly during the whole 12-months study period.

Study Arms (2)

Amoxicillin

EXPERIMENTAL

Amoxicillin (Amoksicillintrihydrat) tablets 750 mg 1x3 for 100 days (oral intake). The tablets will be encapsulated in Capsugel DB-caps AAel Swedish orange.

Drug: Amoxicillin (Amoksicillintrihydrat)

Placebo

PLACEBO COMPARATOR

Placebo capsules for 100 days of daily (1x3), oral intake. The placebo tablets will also be encapsulated in Capsugel DB-caps AAel Swedish orange.

Drug: Placebo

Interventions

Amoxicillin (Amoksicillintrihydrat) DRUG

Amoxicillin tablets 750 mg 1x3 for 100 days (oral intake).

Also known as: Amimox "Meda"

Amoxicillin

Placebo DRUG

Placebo tablets 1x3 for 100 days (oral intake).

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 65 years
• LBP of \> 6 months duration in the area below the 12th rib and above the gluteal folds with a Numerical Rating Scale (NRS) pain intensity score of ³ 5 (mean of three NRS scales; current LBP, the worst LBP within the last 2 weeks, and usual/mean LBP within the last 2 weeks).
• MRI-confirmed lumbar disc herniation within the preceding 2 years.
• MC type I and/or type II in the vertebral body marrow at the same level as the previously herniated disc. For patients with former surgery for disc herniation, the MC has to be located at an operated level.
• Written informed consent

You may not qualify if:

• Allergy to penicillin or cefalosporins
• Allergy/hypersensitivity to any of the excipients of the study drug
• Current pregnancy or lactation
• Elevated kidney (creatinine) or hepatic (ALAT/ASAT) values outside normal range
• Phenylketonuria (Følling disease)
• Mononucleosis or leukaemia
• Any specific diagnosis that may explain patient's low back symptoms (e.g. tumor, fracture, spondyloarthritis, infection, spinal stenosis).
• Former low back surgery (L1 - S1) for other reasons than disc herniation (e.g fusion, decompression, disc prosthesis).
• Former surgery for disc herniation, but \< 12 months have elapsed since surgery.
• Former surgery for disc herniation, but MC located at non-operated level(s) only.
• Reservation against intake of gelatine (the capsules contains gelatine, which among other things is produced by ingredients from pigs)
• Regular use of glucocorticoids
• Regular use of opioids with the exception of codeine and tramadol
• Not understanding Norwegian language
• Unlikely to adhere to treatment and/ or complete follow-up (e.g ongoing serious psychiatric disease, drug abuse, plans to move)

Sponsors & Collaborators

• Oslo University Hospital: lead
• Haukeland University Hospital: collaborator
• St. Olavs Hospital: collaborator
• University Hospital of North Norway: collaborator
• Drammen sykehus: collaborator
• Sykehuset Ostfold: collaborator

Study Sites (1)

Oslo University Hospital Ullevål

Oslo, 0407, Norway

Location

Related Publications (6)

• Storheim K, Espeland A, Grovle L, Skouen JS, Assmus J, Anke A, Froholdt A, Pedersen LM, Haugen AJ, Fors T, Schistad E, Lutro O, Marchand GH, Kadar T, Vetti N, Randen S, Nygaard OP, Brox JI, Grotle M, Zwart JA. Antibiotic treatment In patients with chronic low back pain and Modic changes (the AIM study): study protocol for a randomised controlled trial. Trials. 2017 Dec 15;18(1):596. doi: 10.1186/s13063-017-2306-8.

  PMID: 29246188 BACKGROUND

• Braten LCH, Rolfsen MP, Espeland A, Wigemyr M, Assmus J, Froholdt A, Haugen AJ, Marchand GH, Kristoffersen PM, Lutro O, Randen S, Wilhelmsen M, Winsvold BS, Kadar TI, Holmgard TE, Vigeland MD, Vetti N, Nygaard OP, Lie BA, Hellum C, Anke A, Grotle M, Schistad EI, Skouen JS, Grovle L, Brox JI, Zwart JA, Storheim K; AIM study group. Efficacy of antibiotic treatment in patients with chronic low back pain and Modic changes (the AIM study): double blind, randomised, placebo controlled, multicentre trial. BMJ. 2019 Oct 16;367:l5654. doi: 10.1136/bmj.l5654.

  PMID: 31619437 RESULT

• Braten LCH, Gjefsen E, Gervin K, Pripp AH, Skouen JS, Schistad E, Pedersen LM, Wigemyr M, Selmer KK, Aass HCD, Goll G, Brox JI, Espeland A, Grovle L, Zwart JA, Storheim K; AIM-study group. Cytokine Patterns as Predictors of Antibiotic Treatment Effect in Chronic Low Back Pain with Modic Changes: Subgroup Analyses of a Randomized Trial (AIM Study). J Pain Res. 2023 May 23;16:1713-1724. doi: 10.2147/JPR.S406079. eCollection 2023.

  PMID: 37252109 DERIVED

• Braten LCH, Grovle L, Espeland A, Pripp AH, Grotle M, Helllum C, Haugen AJ, Froholdt A, Rolfsen MP, Nygaard OP, Lutro O, Kristoffersen PM, Anke A, Schistad EI, Skouen JS, Brox JI, Zwart JA, Storheim K; AIM-study group. Clinical effect modifiers of antibiotic treatment in patients with chronic low back pain and Modic changes - secondary analyses of a randomised, placebo-controlled trial (the AIM study). BMC Musculoskelet Disord. 2020 Jul 13;21(1):458. doi: 10.1186/s12891-020-03422-y.

  PMID: 32660517 DERIVED

• Grotle M, Braten LC, Brox JI, Espeland A, Zolic-Karlsson Z, Munk Killingmo R, Tingulstad A, Grovle L, Froholdt A, Kristoffersen PM, Wigemyr M, van Tulder MW, Storheim K, Zwart JA; AIM-study group. Cost-utility analysis of antibiotic treatment in patients with chronic low back pain and Modic changes: results from a randomised, placebo-controlled trial in Norway (the AIM study). BMJ Open. 2020 Jun 15;10(6):e035461. doi: 10.1136/bmjopen-2019-035461.

  PMID: 32546490 DERIVED

• Braten LCH, Schistad EI, Espeland A, Kristoffersen PM, Haugen AJ, Marchand GH, Vetti N, Pripp AH, Kadar TI, Skouen JS, Grotle M, Grovle L, Zwart JA, Brox JI, Storheim K; AIM-study group. Association of Modic change types and their short tau inversion recovery signals with clinical characteristics- a cross sectional study of chronic low back pain patients in the AIM-study. BMC Musculoskelet Disord. 2020 Jun 10;21(1):368. doi: 10.1186/s12891-020-03381-4.

  PMID: 32522268 DERIVED

MeSH Terms

Conditions

Low Back Pain; Bronchiolitis Obliterans Syndrome

Interventions

Amoxicillin

Condition Hierarchy (Ancestors)

Back Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Intervention Hierarchy (Ancestors)

Ampicillin; Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Kjersti Storheim, PhD

  Oslo University Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of section

Study Record Dates

• First Submitted: November 21, 2014
• First Posted: December 23, 2014
• Study Start: June 1, 2015
• Primary Completion: September 21, 2018
• Study Completion: November 6, 2018
• Last Updated: September 27, 2021

Record last verified: 2021-09

Locations

NO (1)