Clinical trial NCT06771492: Efficacy of Antibiotic Treatment for Patients with Chronic Low Back Pain and Modic Type I Changes - Randomized Placebo-controlled Trial
Official title: Efficacy of Antibiotic Treatment for Patients with Chronic Low Back Pain and Modic Type I Changes - Randomized Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: MSK Conditions
Chronic Low Back Pain (CLBP)
Modic Changes
Keywords: Antibiotics
Amoxicillin
Low back pain (LBP)
Modic changes
Randomized controlled trial
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
Collaborators: name: Erasmus University Rotterdam
First posted: 2025-01-13
Enrollment: 204
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Roland Morris Disability Questionnaire (RMDQ)
timeFrame: The measurements are scheduled at baseline and at 3, 6 and 12 months follow-up.
Secondary outcomes:
measure: LBP-intensity (0-10 NRS-scale)
timeFrame: Measured at baseline, 3 months, 6 months and 12 months
measure: Leg pain intensity (0-10 NRS-scale)
timeFrame: Measured at baseline, 3 months, 6 months and 12 months
measure: Health-related quality of life (PROMIS-GH-10)
timeFrame: Measured at baseline, 3 months, 6 months and 12 months
measure: Health-related quality of life (EQ-5D-5L)
timeFrame: Measured at baseline, 3 months, 6 months and 12 months
measure: Self-reported number of days with sick leave
timeFrame: Measured at baseline, 3 months, 6 months and 12 months
measure: Co-interventions (pharmacological and non-pharmacological)
timeFrame: Measured at baseline, 3 months and 12 months
measure: Global perceived effect (7-point Likert scale)
timeFrame: Measured at 3 months, 6 months and 12 months
measure: Patients' satisfaction with treatment (7-point Likert scale)
timeFrame: Measured at baseline, 3 months and 12 months
measure: Success of blinding
timeFrame: Measured at 3 months and 12 months
measure: Compliance
timeFrame: Measured at 3 months
measure: Pain self-efficacy (Pain Self-Efficacy Questionnaire)
timeFrame: Measured at baseline, 3 months, 6 months and 12 months
measure: Sleep questionnaire (Pittsburgh Sleep Quality Index)
timeFrame: Measured at baseline, 3 months, 6 months and 12 months
measure: Neuropathic pain (PainDETECT)
timeFrame: Measured at baseline, 3 months, 6 months and 12 months
measure: Cost questionnaires (Medical Consumption Questionnaire)
timeFrame: Measured at 3 months, 6 months and 12 months
measure: Cost questionnaires (Productivity Cost Questionnaire)
timeFrame: Measured at 3 months, 6 months and 12 months
measure: Gut microbiome composition
timeFrame: Measured at baseline, 3 months, and 12 months
Other outcomes:
Locations:
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
state: Zuid-Holland
Study officials:
References:
citation: GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018 Nov 10;392(10159):1789-1858. doi: 10.1016/S0140-6736(18)32279-7. Epub 2018 Nov 8. Erratum In: Lancet. 2019 Jun 22;393(10190):e44. doi: 10.1016/S0140-6736(19)31047-5.
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citation: Albert HB, Sorensen JS, Christensen BS, Manniche C. Antibiotic treatment in patients with chronic low back pain and vertebral bone edema (Modic type 1 changes): a double-blind randomized clinical controlled trial of efficacy. Eur Spine J. 2013 Apr;22(4):697-707. doi: 10.1007/s00586-013-2675-y. Epub 2013 Feb 13.
citation: 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.
citation: Oliveira CB, Maher CG, Pinto RZ, Traeger AC, Lin CC, Chenot JF, van Tulder M, Koes BW. Clinical practice guidelines for the management of non-specific low back pain in primary care: an updated overview. Eur Spine J. 2018 Nov;27(11):2791-2803. doi: 10.1007/s00586-018-5673-2. Epub 2018 Jul 3.
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