Bone Resorption, Osteoclastogenesis and Adalimumab (BROCAII)
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|ClinicalTrials.gov Identifier: NCT02035800|
Recruitment Status : Recruiting
First Posted : January 14, 2014
Last Update Posted : May 8, 2018
|Condition or disease||Intervention/treatment||Phase|
|RheumatoId Arthritis||Drug: Adalimumab||Phase 4|
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 :||Interventional (Clinical Trial)|
|Estimated Enrollment :||120 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Bone Resorption, Osteoclastogenesis and Adalimumab|
|Study Start Date :||May 2013|
|Estimated Primary Completion Date :||December 2018|
|Estimated Study Completion Date :||December 2019|
Experimental: Adalimumab (humira)
As standard of care.
Patient will received medication as standard of care
Other Name: Humira
- 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.
- 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
- 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
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02035800
|Contact: Artur Fernandes||819-346-1110 ext 15417||Artur.Jose.De.B.Fernandes@USherbrooke.ca|
|Contact: Gilles Boire||819-346-1110 ext 15063||Gilles.Boire@usherbrooke.ca|
|CRC Étienne Le-Bel at CHUS||Recruiting|
|Sherbrooke, Quebec, Canada, J1H 5N4|
|Contact: Stéphanie Mcmahon 819-346-1110 ext 12845|
|Contact: Maryse Berthiaume 819-346-1110 ext 12891|
|Principal Investigator: Artur Fernandes|
|Principal Investigator:||Artur Ferandnes||Centre de recherche Étienne Le-Bel at Centre hospitalier universitaire de Sherbrooke|