- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02035800
Bone Resorption, Osteoclastogenesis and Adalimumab (BROCAII)
Study Overview
Detailed Description
Osteoclasts (OC) are clearly involved in joint destruction in Rheumatoid Arthritis (RA), as shown by clinical and experimental data. Tumor Necrosis Factor Alpha (TNF-alpha), a major pathologic mediator in RA, may induce bone resorption either directly, stimulating osteoclastogenesis or indirectly, by influencing receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG) and prostaglandin production by osteoblasts. Anti-TNF agents reduce bone destruction in RA but their effects on osteoclast biology in patients with RA are little known.
The original BROCA study, which included a cohort of 25 RA patients, aimed to study the effect of treatment with Adalimumab on times zero, 3 and 6 months on the following osteoclastic parameters: 1) the number of osteoclast precursor (CD14+) cells in the peripheral blood, 2) the number of osteoclasts generated in vitro, and 3) the amount of bone resorption in vitro before, 3 and 6 months after treatment with Adalimumab. The secondary outcomes were 1) The effect of treatment with Adalimumab on disease activity score defined as a DAS28 score (Disease Activity Score, 2) The effect of treatment with Adalimumab (also name: Humira) on change in functional status by the health assessment questionnaire (HAQ), and 3) Parallel in vitro differentiation assays (number of osteoclasts generated and amount of bone resorption) in the presence of exogenous Adalimumab in the concentration range found in the plasma of treated patients to detect a direct effect of the medication in vitro in osteoclastogenesis.
The results showed that treatment with Adalimumab induced a statistically significant reduction in the clinical scores DAS28 and HAQ, as has been shown by many clinical studies . Even though no statistically significant effect of the treatment was found on the number of osteoclast precursors, the number of osteoclasts generated in vitro or the surface of bone resorption in vitro, there was a clear trend towards a decrease in the last two parameters. We believe this lack of statistical significance is due to a type II error, a consequence of the much higher variance of the primary parameter (number of in vitro-generated osteoclasts) in the patient cohort than we could foresee from the initial data from normal donors. Moreover, there was a statistically significant correlation (p=0.416, linear regression) between the difference in the number of osteoclasts in time zero and six months and the difference in the HAQ score, which not only supports the hypothesis that the treatment with Adalimumab may be associated with a reduction in the number of osteoclasts but also suggests that this reduction may be associated with a better response to the treatment. The general objective of the proposed prolongation of the BROCA study is to verify these two working hypothesis.
Study Type
Enrollment (Anticipated)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Quebec
-
Sherbrooke, Quebec, Canada, J1H 5N4
- Recruiting
- CRC Étienne Le-Bel at CHUS
-
Contact:
- Stéphanie Mcmahon
- Phone Number: 12845 819-346-1110
-
Contact:
- Maryse Berthiaume
- Phone Number: 12891 819-346-1110
-
Principal Investigator:
- Artur Fernandes
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patients aged of 18 and over,
- Satisfying the 1987 American College of Rheumatology (ACR) criteria for RA
- Receiving a prescription of Adalimumab 40 mg subcutaneous every two weeks.
Exclusion Criteria:
- Patients not capable or willing to provide informed consent
- Patients starting Adalimumab less than five half-lives after the interruption of a previous anti-TNF therapy.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Adalimumab (humira)
As standard of care.
|
Patient will received medication as standard of care
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Verify if the treatment with Adalimumab may be associated with a reduction in the number of osteoclasts.
Time Frame: 6 months after treatment
|
By calculating the number of osteoclast and osteoblast in patient serum.
|
6 months after treatment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Verify if this reduction may be associated with a better response to the treatment.
Time Frame: 6 months after treatment
|
Disease activity defined as a DAS28 score
|
6 months after treatment
|
To verify reduction of osteoclasts may be associated with a better response to the treatment.
Time Frame: 6 months after treatment
|
Functional status by the HAQ
|
6 months after treatment
|
To verify reduction of osteoclasts may be associated with a better response to the treatment.
Time Frame: 6 months after traitment
|
Radiological progression defined by Sharp scores
|
6 months after traitment
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Artur Ferandnes, Centre de recherche Étienne Le-Bel at Centre hospitalier universitaire de Sherbrooke
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- IMM 11-0163
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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