Chronic Non-bacterial Osteomyelitis Treated With Pamidronate

Musculoskeletal Disease Clinical Trial

— CNOPAM  

Official title:

Chronic Non-bacterial Osteomyelitis Treated With Pamidronate in a Randomised Placebo Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02594878
• Other study ID #: 48438
• Status: Recruiting
• Phase: Phase 2
• First received: October 20, 2015
• Last updated: November 15, 2016
• Start date: October 2015
• Est. completion date: August 2018

Study information

• Verified date: November 2016
• Source: University of Aarhus
• Contact: Caroline Marie Andreasen, MD
• Phone: +45 7846 4252
• Email: carand[@]rm.dk
• Is FDA regulated: No
• Health authority: Denmark: Danish Dataprotection AgencyDenmark: Ministry of HealthDenmark: The Regional Committee on Biomedical Research Ethics
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: August 2018
• Est. primary completion date: May 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 9 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Immune System Disease
• Immune System Diseases
• Musculoskeletal Disease
• Musculoskeletal Diseases
• Osteomyelitis

Intervention

Drug:
• Pamidronatdinatrium

Other:
• Natrium chloride 9mg/ml

Locations

Country	Name	City	State
Denmark	Universityhospital of Aarhus, Denmark	Aarhus

Sponsors (1)

Lead Sponsor	Collaborator
University of Aarhus

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Wholebody MRI		Changes between baseline and week 36	No
Secondary	CT scan of the anterior chestwall (adults)		Changes between baseline and week 36	No
Secondary	Systemic inflammatory markers	TNF- a,IL-1 ß, IL-8, IL-18, IL-17, INF-?, IL-6, IL-10, IL-11, IL-21, MIP 1-alfa (CCL3, 22) and IL-1Ra	Changes between baseline and week 1, 4, 12, 24 and 36	No
Secondary	Systemic bone markers	s-CTX og s-NTX, P1NP, C1NP, TRACP 5b, bone alkaline phosphatase	Changes between baseline and week 1, 4, 12, 24 and 36	No
Secondary	Wholebody MRI		Changes between baseline and week 12 and changes between week 12 and 36	No
Secondary	Changes in Health Assesment Questionnaire score		Changes between baseline and week 1, 4, 12, 24 and 36	No
Secondary	Changes in Children Assesment Questionnaire score		Changes between baseline and week 1, 4, 12, 24 and 36	No
Secondary	Changes in Visual Analog Score for pain		Changes between baseline and week 1, 4, 12, 24 and 36	No