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Bone Resorption, Osteoclastogenesis and Adalimumab (BROCAII)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02035800
Recruitment Status : Unknown
Verified May 2018 by Université de Sherbrooke.
Recruitment status was:  Recruiting
First Posted : January 14, 2014
Last Update Posted : May 8, 2018
Sponsor:
Collaborator:
AbbVie
Information provided by (Responsible Party):
Université de Sherbrooke

Tracking Information
First Submitted Date  ICMJE December 10, 2013
First Posted Date  ICMJE January 14, 2014
Last Update Posted Date May 8, 2018
Study Start Date  ICMJE May 2013
Estimated Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 13, 2014)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 13, 2014)
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Bone Resorption, Osteoclastogenesis and Adalimumab
Official Title  ICMJE Bone Resorption, Osteoclastogenesis and Adalimumab
Brief Summary Broca II is the prolongation of the original study name BROCA. In BROCA study, only 25 patients participated and it was not enough to concluded clearly our hypothesis.
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  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE RheumatoId Arthritis
Intervention  ICMJE Drug: Adalimumab
Patient will received medication as standard of care
Other Name: Humira
Study Arms  ICMJE Experimental: Adalimumab (humira)
As standard of care.
Intervention: Drug: Adalimumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: January 13, 2014)
120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2019
Estimated Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02035800
Other Study ID Numbers  ICMJE IMM 11-0163
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Université de Sherbrooke
Study Sponsor  ICMJE Université de Sherbrooke
Collaborators  ICMJE AbbVie
Investigators  ICMJE
Principal Investigator: Artur Ferandnes Centre de recherche Étienne Le-Bel at Centre hospitalier universitaire de Sherbrooke
PRS Account Université de Sherbrooke
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP