BackToBasic: Infliximab in Chronic Low Back Pain and Modic Changes

NCT03704363 | Completed Phase 3

• 1 other identifier: 2017/2450
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 6

Brief Summary

Low-Back Pain (LBP) is the leading cause of disability worldwide. Even though LBP relates to different underlying pathologies, there are a substantial number of patients with chronic complaints that have vertebral bone marrow lesions visualized as Modic changes (MC) on magnetic resonance imaging (MRI). Despite the clinical evidence that MC is painful, the etiology is unknown and there is currently no established treatment. It has been suggested that MCs are secondary to a biomechanically induced degradation with a subsequent autoimmune response, supported by evidence showing that Tumor necrosis factor (TNF)-α plays a critical role in intervertebral disc degeneration and MCs. Clinical trials suppressing inflammation with TNF-alfa blockers in patients with acute low back pain and sciatica provide evidence to support the initiation of a clinical trial assessing the effect of TNF-alfa blockers in patients with chronic low-back pain and MCs. Since TNF-alfa blockers is an established treatment for immune-mediated disorders like spondyloarthritis by reducing pain as well as bone marrow lesions, the researchers aim to assess whether this treatment is effective for chronic LBP with MCs. In addition refine diagnostic assessment and explore potential biomarkers, which will provide an increased understanding of underlying factors causing LBP, and ultimately result in better management and treatment for one of the most costly and challenging patient populations.

Conditions

Low Back Pain

Keywords

Modic changes; biomarkers; treatment; infliximab; chronic low back pain

Outcome Measures

Primary Outcomes (1)

• Change in Oswestry Disability Index (ODI) from baseline to 5 months

  ODI is a disease-specific disability score. Scale is measured 0-100, better to worse respectively.

  0, 1, 2, 3, 4, 5 and 9 months

Secondary Outcomes (7)

• Change in Short tau inversion recovery (STIR) signal (intensity and extent) of Modic Changes from baseline to 5 months.

  0 and 5-6 months

• Change in low back pain intensity from baseline to 5 months

  0 + weekly during intervention period, 3, 5 and 9 months

• Change in Roland Morris Disability Questionnaire (RMDQ) from baseline to 5 months

  0, 3, 5 and 9 months

• Change in Health-related quality of life from baseline to 5 months

  0, 3, 5 and 9 months

• Number and type of co-interventions (other pharmacological treatment (ATC-coded) and non-pharmacological treatment)

  Will be registered every month up to 5 months and at 9 months

Other Outcomes (6)

• Change in Leg pain intensity from baseline to 5 months

  0, 3, 5 and 9 months

• Change in Hours with low back pain during the last 4 weeks from baseline to 5 months

  0, 3, 5 and 9 months

• Change in Symptom-specific well-being from baseline to 5 months

  0, 3, 5 and 9 months

Study Arms (2)

Infliximab

EXPERIMENTAL

Intravenous infusion(biosimilar infliximab). Each participant will be given 4 infusions, at day 0, day 14, day 42 and day 98, unless unacceptable toxicity is encountered.

Drug: Biosimilar Infliximab

Placebo

PLACEBO COMPARATOR

Intravenous infusion (NaCl intravenous infusion). Each participant will be given 4 infusions, at day 0, day 14, day 42 and day 98.

Other: Placebo

Interventions

Biosimilar Infliximab DRUG

Intravenous infusion(5 mg/kg). Each participant will be given 4 infusions, at day 0, day 14, day 42 and day 98, unless unacceptable toxicity is encountered.

Infliximab

Placebo OTHER

Intravenous infusion. Each participant will be given 4 infusions, at day 0, day 14, day 42 and day 98,

Also known as: NaCl intravenous infusion

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 \> 50% of days for \> 6 months duration in the area below the 12th rib and above the gluteal folds with:
• Numerical Rating Scale (NRS) pain intensity score of at least 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) and/or ODI-score of at least 25
• \- Modic change of craniocaudal size \>= 10% of vertebral height and of primary or secondary type 1 in the vertebral body at a level of the lumbar spine (superior or inferior endplate, Th12-S1).

You may not qualify if:

• Fever or ongoing infection
• Allergy or hypersensitivity against any products of the medication
• Previous infliximab treatment
• Any serious adverse events with other immunosuppressive treatment (including cytostatics, antibodies, drugs acting on immunophilins, Interferons, mycophenolate and any other DMARDs)
• 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 or decompression (e.g fusion, disc prosthesis).
• Former surgery for disc herniation or decompression within the last 12 months
• Any known rheumatic disease
• Current pregnancy or lactation
• For women of childbearing potential (WOCBP); inadequate birth control, pregnancy, and/or breastfeeding. WOCBP is defined as those who are fertile (with uterus, fallopian tubes and at least one intact functional ovary), following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. Documentation of surgical procedure or physical examination is required for subjects who have had such an operation. Adequate contraception must be used by WOCBP during the entire intervention period and 6 months after the last administration of study drug, and includes oral, injected or implanted hormonal methods of contraception, placement of an intrauterine device or system, vasectomized partner or sexual abstinence.
• Ongoing systemic glucocorticoid or other immunosuppressive treatments (see list above)
• Regular use of opioids with the exception of codeine and tramadol
• Other immunosuppressive treatment last year (see list above)
• Active or latent (known or suspected) tuberculosis (all participants will be screened for latent tuberculosis)
• Previous infection with Hepatitis B virus (HBV) (all participants will be screened for HBV-carrier state)

Sponsors & Collaborators

• Oslo University Hospital: lead
• Haukeland University Hospital: collaborator
• St. Olavs Hospital: collaborator
• University Hospital of North Norway: collaborator
• Vestre Viken Hospital Trust: collaborator
• Ostfold Hospital Trust: collaborator
• Clinical Trial Unit (CTU), Oslo University Hospital: collaborator
• Diakonhjemmet Hospital: collaborator

Study Sites (6)

Haukeland University Hospital

Bergen, Norway

Location

Vestre Viken Hospital Trust Drammen

Drammen, Norway

Location

Østfold Hospital Trust

Moss, Norway

Location

Oslo University Hospital Ullevål

Oslo, 0407, Norway

Location

University Hospital of North Norway

Tromsø, Norway

Location

St. Olavs Hospital

Trondheim, Norway

Location

Related Publications (1)

• Gjefsen E, Braten LCH, Goll GL, Wigemyr M, Bolstad N, Valberg M, Schistad EI, Marchand GH, Granviken F, Selmer KK, Froholdt A, Haugen AJ, Dagestad MH, Vetti N, Bakland G, Lie BA, Haavardsholm EA, Nilsen AT, Holmgard TE, Kadar TI, Kvien T, Skouen JS, Grovle L, Brox JI, Espeland A, Storheim K, Zwart JA. The effect of infliximab in patients with chronic low back pain and Modic changes (the BackToBasic study): study protocol of a randomized, double blind, placebo-controlled, multicenter trial. BMC Musculoskelet Disord. 2020 Oct 21;21(1):698. doi: 10.1186/s12891-020-03720-5.

  PMID: 33087100 DERIVED

MeSH Terms

Conditions

Low Back Pain

Condition Hierarchy (Ancestors)

Back Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Anne Froholdt, PhD

  Vestre Viken Hospital Trust Drammen

  PRINCIPAL INVESTIGATOR

• Anne Julsrud Haugen, PhD

  Ostfold Hospital Trust

  PRINCIPAL INVESTIGATOR

• Jan Sture Skouen, PhD

  Haukeland University Hospital

  PRINCIPAL INVESTIGATOR

• Jens Ivar Brox, PhD

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

• Gunn Hege Marchand, PhD

  St. Olavs Hospital, Trondheim

  PRINCIPAL INVESTIGATOR

• Gunnstein Bakland, PhD

  University Hospital of North Norway Tromsø

  PRINCIPAL INVESTIGATOR

• John-Anker Zwart, PhD

  Oslo University Hospital, Oslo, Norway

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: A computer-generated randomised allocation sequence will be imported into an electronic case report form (eCRF) system (Viedoc) and made available exclusively to a study nurse (mixing nurse) authorised by the local principal investigator to prepare infusions. The mixing nurse is otherwise not involved in the treatment of the patient. The infusion bags containing the study medication will be prepared by the mixing nurse in identical infusion bags, and applied labels with patient number and dose such that blinding of the participants is secured. The Investigational Medicinal Products (IMPs) have the same color and will look the same. After preparing the IMP, the mixing nurse will hand over the IMP to another nurse, blinded to allocation, and authorised by the local principal investigator to administer the infusion.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Oslo University Hospital

Study Record Dates

• First Submitted: September 19, 2018
• First Posted: October 12, 2018
• Study Start: December 12, 2018
• Primary Completion: July 27, 2023
• Study Completion: September 29, 2023
• Last Updated: March 8, 2024

Record last verified: 2024-03

Locations

NO (6)