Chronic Non-bacterial Osteomyelitis Treated With Pamidronate (CNOPAM)
Primary Purpose
Immune System Disease, Musculoskeletal Disease
Status
Unknown status
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
Pamidronatdinatrium
Natrium chloride 9mg/ml
Sponsored by
About this trial
This is an interventional treatment trial for Immune System Disease focused on measuring Chronic non-bacterial osteomyelitis, Chronic recurrent multifocal osteomyelitis, Non- bacterial osteomyelitis, SAPHO syndrome, Whole body MRI, Pamidronate, Inflammatory bone disease, Autoinflammatory disease
Eligibility Criteria
Inclusion Criteria:
- Age: 9-65 years (inclusive)
Fulfilling the diagnostic criteria for chronic non bacterial osteomyelitis:
- Mono-, oligo- or multifocal inflammatory bone lesions (osteomyelitis, osteitis, osteosclerosis)
- Diagnostic score according to A. Jansson criteria (2009) > 39 or malignancy and infection excluded by biopsy
- 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
Sites / Locations
- Universityhospital of Aarhus, DenmarkRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Pamidronatdinatrium 3mg/ml
Natrium chloride 9 mg/ml
Arm 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.
Natrium chloride 9 mg/ml volume equals experimental drug
Outcomes
Primary Outcome Measures
Wholebody MRI
Secondary Outcome Measures
CT scan of the anterior chestwall (adults)
Systemic inflammatory markers
TNF- α,IL-1 β, IL-8, IL-18, IL-17, INF-ƴ, IL-6, IL-10, IL-11, IL-21, MIP 1-alfa (CCL3, 22) and IL-1Ra
Systemic bone markers
s-CTX og s-NTX, P1NP, C1NP, TRACP 5b, bone alkaline phosphatase
Wholebody MRI
Changes in Health Assesment Questionnaire score
Changes in Children Assesment Questionnaire score
Changes in Visual Analog Score for pain
Full Information
NCT ID
NCT02594878
First Posted
October 20, 2015
Last Updated
November 15, 2016
Sponsor
University of Aarhus
1. Study Identification
Unique Protocol Identification Number
NCT02594878
Brief Title
Chronic Non-bacterial Osteomyelitis Treated With Pamidronate
Acronym
CNOPAM
Official Title
Chronic Non-bacterial Osteomyelitis Treated With Pamidronate in a Randomised Placebo Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
November 2016
Overall Recruitment Status
Unknown status
Study Start Date
October 2015 (undefined)
Primary Completion Date
May 2018 (Anticipated)
Study Completion Date
August 2018 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Aarhus
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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:
Reduction of the inflammatory activity in the bone lesions measured by whole body MRI after 36 weeks.
Healing of the inflammatory activity in the bone lesions measured by whole body MRI after 36 weeks.
Secondary objectives:
Changes in bone lesions in whole body MRI between baseline and week 12 and between week 12 and week 36
Changes in bone lesions of anterior chest-wall (adults) evaluated by CT scan between baseline and week 36.
Changes in patient self reported outcome measures
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
32 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Pamidronatdinatrium 3mg/ml
Arm Type
Experimental
Arm 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.
Arm Title
Natrium chloride 9 mg/ml
Arm Type
Placebo Comparator
Arm Description
Natrium chloride 9 mg/ml volume equals experimental drug
Intervention Type
Drug
Intervention Name(s)
Pamidronatdinatrium
Other Intervention Name(s)
Pamidronat, Pamifos, Aredia
Intervention Type
Other
Intervention Name(s)
Natrium chloride 9mg/ml
Primary Outcome Measure Information:
Title
Wholebody MRI
Time Frame
Changes between baseline and week 36
Secondary Outcome Measure Information:
Title
CT scan of the anterior chestwall (adults)
Time Frame
Changes between baseline and week 36
Title
Systemic inflammatory markers
Description
TNF- α,IL-1 β, IL-8, IL-18, IL-17, INF-ƴ, IL-6, IL-10, IL-11, IL-21, MIP 1-alfa (CCL3, 22) and IL-1Ra
Time Frame
Changes between baseline and week 1, 4, 12, 24 and 36
Title
Systemic bone markers
Description
s-CTX og s-NTX, P1NP, C1NP, TRACP 5b, bone alkaline phosphatase
Time Frame
Changes between baseline and week 1, 4, 12, 24 and 36
Title
Wholebody MRI
Time Frame
Changes between baseline and week 12 and changes between week 12 and 36
Title
Changes in Health Assesment Questionnaire score
Time Frame
Changes between baseline and week 1, 4, 12, 24 and 36
Title
Changes in Children Assesment Questionnaire score
Time Frame
Changes between baseline and week 1, 4, 12, 24 and 36
Title
Changes in Visual Analog Score for pain
Time Frame
Changes between baseline and week 1, 4, 12, 24 and 36
10. Eligibility
Sex
All
Minimum Age & Unit of Time
9 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age: 9-65 years (inclusive)
Fulfilling the diagnostic criteria for chronic non bacterial osteomyelitis:
Mono-, oligo- or multifocal inflammatory bone lesions (osteomyelitis, osteitis, osteosclerosis)
Diagnostic score according to A. Jansson criteria (2009) > 39 or malignancy and infection excluded by biopsy
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Caroline Marie Andreasen, MD
Phone
+45 7846 4252
Email
carand@rm.dk
First Name & Middle Initial & Last Name or Official Title & Degree
Ellen Margrethe Hauge, Professor
Phone
+45 7846 4252
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Caroline Marie Andreasen, MD
Organizational Affiliation
University hospital of Aarhus, Denmark
Official's Role
Principal Investigator
Facility Information:
Facility Name
Universityhospital of Aarhus, Denmark
City
Aarhus
ZIP/Postal Code
8000
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Caroline Marie Andreasen, MD
Phone
+4578464252
Email
carand@rm.dk
12. IPD Sharing Statement
Citations:
PubMed Identifier
32484386
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.
Results Reference
derived
Learn more about this trial
Chronic Non-bacterial Osteomyelitis Treated With Pamidronate
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