Efficacy and safety of pamidronate in Modic type 1 changes: study protocol for a prospective randomized controlled clinical trial

Abstract

BackgroundErosive degenerative disc disease, also known as Modic type 1 changes, is usually characterized by low back pain with an inflammatory pain pattern, as seen in spondyloarthropathies. Intravenous pamidronate has proven to be effective in patients with ankylosing spondylitis who are refractory to nonsteroidal antiinflammatory drugs, and in painful bone diseases in general, such as Paget’s disease, fibrous dysplasia or vertebral fractures. We therefore hypothesize that pamidronate would be effective in treating low back pain associated with Modic type 1 changes.Methods/DesignThis study, called PEPTIDE (short for the French title “Etude Prospective sur l’Efficacité et la tolérance du PamidronaTe dans les dIscopathies Degeneratives Erosives”), will be a double-blind, randomized, placebo-controlled, parallel group, phase two clinical trial. A total of 48 patients will be recruited. These patients will be randomly assigned to one of the two groups, with 24 patients in each group: one group will be given pamidronate and the other a placebo. Pamidronate will be administered at a dose of 90 mg per day for two days consecutively, and every patient, irrespective of treatment group, will be given paracetamol to maintain blinding by preventing drug-induced fever. The primary outcome measure is a between-group difference of 30 points on a 100 mm Visual Analogue Scale (VAS) at three months. Secondary outcome measures are improvement in functional status and the drug’s safety. Primary and secondary outcome measures will be assessed at each visit (inclusion, at six weeks, three months, and six months). If the primary goal is not attained, the patient will be offered a rigid or semi-rigid back brace, irrespective of the treatment group.DiscussionTo date, only local treatments, for example intradiscal corticosteroid therapy, lumbar arthrodesis or back braces have been studied in randomized, controlled trials, with controversial results. This trial is currently ongoing and, if conclusive, should provide physicians with an acceptable alternative to those treatments. The results should be publicly available in spring 2015.Trial registrationClinicalTrials.gov number, NCT01799616.

From Modic 1 vertebral-endplate subchondral bone signal changes detected by MRI to the concept of ‘active discopathy’

“…Results of an open study seem to be encouraging52; a randomised controlled trial of 5 mg zoledronic acid found a significant improvement in LBP at 1 month,53 and a randomised controlled trial of 90 mg pamidronate, for 2 days consecutively, is ongoing 54. Other therapeutic options targeting bone marrow oedema such as surgical decompression or the prostaglandin analogue iloprost have not been assessed yet.…”

Impact of an Awareness Campaign for the Detection of Axial Spondyloarthritis in Patients with Inflammatory Back Pain

“…Fourteen out of 40 (35%) patients did not meet AxSpA criteria, and IBP could be explained by another cause: 100% had Degenerative Disc Disease (DDD). Although DDD tends to present with chronic mechanic lumbar pain, Modic I disc diseases may manifest with IBP characteristics [33,34]. In addition, DDD is most frequently found in older patients, not associated to acute phase reactant changes.…”