Chronic Non-bacterial Osteomyelitis Treated With Pamidronate (CNOPAM)

University of Aarhus

Status and phase: Unknown; Phase 2

Conditions: Immune System Disease; Musculoskeletal Disease

Treatments: Other: Natrium chloride 9mg/ml; Drug: Pamidronatdinatrium

Study type: Interventional

Funder types: Other

Identifiers

NCT02594878

48438

Details and patient eligibility

About

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.

Full 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.

Enrollment: 32 estimated patients

Sex: All

Ages: 9 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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32 participants in 2 patient groups, including a placebo group

Pamidronatdinatrium 3mg/ml

Experimental group

Description:

Pamidronatdinatrium 1 mg/kg max 60 mg for 3 days every 3 month in total of 3 series (0,3,6 month). First day first series 0,5mg/kg max 30 mg.

Treatment:

Drug: Pamidronatdinatrium

Natrium chloride 9 mg/ml

Placebo Comparator group

Description:

Natrium chloride 9 mg/ml volume equals experimental drug

Treatment:

Other: Natrium chloride 9mg/ml