Clinical trial NCT02594878: Chronic Non-bacterial Osteomyelitis Treated With Pamidronate
Official title: Chronic Non-bacterial Osteomyelitis Treated With Pamidronate in a Randomised Placebo Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Immune System Disease
Musculoskeletal Disease
Keywords: Chronic non-bacterial osteomyelitis
Chronic recurrent multifocal osteomyelitis
Non- bacterial osteomyelitis
SAPHO syndrome
Whole body MRI
Pamidronate
Inflammatory bone disease
Autoinflammatory disease
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2015-11-03
Enrollment: 32
Sex: ALL
Minimum age (years): 9
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In a randomized double blind placebo controlled trial to investigate the effect of pamidronate in treatment of chronic non bacterial osteomyelitis.

Main objective:

1. Reduction of the inflammatory activity in the bone lesions measured by whole body MRI after 36 weeks.
2. Healing of the inflammatory activity in the bone lesions measured by whole body MRI after 36 weeks.

Secondary objectives:

1. Changes in bone lesions in whole body MRI between baseline and week 12 and between week 12 and week 36
2. Changes in bone lesions of anterior chest-wall (adults) evaluated by CT scan between baseline and week 36.
3. Changes in patient self reported outcome measures
4. Changes in inflammatory markers and bone markers.

Detailed description: Chronic non-bacterial osteomyelitis is a multifocal inflammatory bone disorder. The pathogenesis is unknown. The disease is mainly diagnosed in childhood. There is a strong association with inflammatory disorders of the skin, mainly psoriasis. The disease is characterized by recurrent episodes of pain and disability. It is unclear if SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis) might be the adult version of chronic non-bacterial osteomyelitis. The disease can persist in adulthood and course chronic bone deformations.

Wholebody MRI is the most sensitive imaging for diagnosing and monitoring the non bacterial osteitis.

The treatment of chronic non-bacterial osteomyelitis is largely empiric. First line treatment is NSAID (Non Steroidal Anti-Inflammatory Drug). When NSAID is inadequate the bisphosphonate pamidronate has been described relief pain in small cohorts in retrospective studies.

In this research protocol, investigators seek to investigate if it is beneficial to use pamidronate in the treatment of chronic non bacterial osteomyelitis and the osteitis component in SAPHO syndrome. Primary outcome is whole body MRI. Secondary outcome is CT scan, patient measure reported outcome and biomarkers. A biobank may help us to understand the pathogenesis and future treatment targets of chronic non bacterial osteomyelitis.

Eligibility criteria: Inclusion Criteria:

* Age: 9-65 years (inclusive)
* Fulfilling the diagnostic criteria for chronic non bacterial osteomyelitis:

  1. Mono-, oligo- or multifocal inflammatory bone lesions (osteomyelitis, osteitis, osteosclerosis)
  2. Diagnostic score according to A. Jansson criteria (2009) \> 39 or malignancy and infection excluded by biopsy
  3. Symptoms \> 6 weeks
* Volunteer, signed written informed content

Exclusion Criteria:

* Age older than 65 years
* Age younger than 9 years
* Pregnant women or nursing (breastfeeding) mothers
* Hypersensitivity to pamidronate, bisphosphonate og additives in pamidronate
* Known history or current lymphoproliferative disease
* History of surgery on glandula thyroidea
* Known alcohol/medical abuse
* Poor dental status
* Low Vitamin D- status
* Liver/ kidney disease
* Abnormal laboratory screening for comorbidity

Primary outcomes:
measure: Wholebody MRI
timeFrame: Changes between baseline and week 36
Secondary outcomes:
measure: CT scan of the anterior chestwall (adults)
timeFrame: Changes between baseline and week 36
measure: Systemic inflammatory markers
timeFrame: Changes between baseline and week 1, 4, 12, 24 and 36
measure: Systemic bone markers
timeFrame: Changes between baseline and week 1, 4, 12, 24 and 36
measure: Wholebody MRI
timeFrame: Changes between baseline and week 12 and changes between week 12 and 36
measure: Changes in Health Assesment Questionnaire score
timeFrame: Changes between baseline and week 1, 4, 12, 24 and 36
measure: Changes in Children Assesment Questionnaire score
timeFrame: Changes between baseline and week 1, 4, 12, 24 and 36
measure: Changes in Visual Analog Score for pain
timeFrame: Changes between baseline and week 1, 4, 12, 24 and 36
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Universityhospital of Aarhus, Denmark
Study officials:
affiliation: University hospital of Aarhus, Denmark
name: Caroline Marie Andreasen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Andreasen CM, Jurik AG, Deleuran BW, Horn HC, Folkmar TB, Herlin T, Hauge EM. Pamidronate in chronic non-bacterial osteomyelitis: a randomized, double-blinded, placebo-controlled pilot trial. Scand J Rheumatol. 2020 Jul;49(4):312-322. doi: 10.1080/03009742.2020.1724324. Epub 2020 Jun 2.