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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
Sponsor:
Collaborator:
AbbVie
Information provided by (Responsible Party):
Université de Sherbrooke

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.

Condition or disease Intervention/treatment Phase
RheumatoId Arthritis Drug: Adalimumab Phase 4

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 : 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

Resource links provided by the National Library of Medicine

Drug Information available for: Adalimumab

Arm Intervention/treatment
Experimental: Adalimumab (humira)
As standard of care.
Drug: Adalimumab
Patient will received medication as standard of care
Other Name: Humira




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

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


Contacts
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

Locations
Canada, Quebec
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         
Sponsors and Collaborators
Université de Sherbrooke
AbbVie
Investigators
Principal Investigator: Artur Ferandnes Centre de recherche Étienne Le-Bel at Centre hospitalier universitaire de Sherbrooke

Responsible Party: Université de Sherbrooke
ClinicalTrials.gov Identifier: NCT02035800     History of Changes
Other Study ID Numbers: IMM 11-0163
First Posted: January 14, 2014    Key Record Dates
Last Update Posted: May 8, 2018
Last Verified: May 2018

Keywords provided by Université de Sherbrooke:
Rheumatoid Arthritis
Adalimumab
Humira

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Bone Resorption
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Bone Diseases
Adalimumab
Anti-Inflammatory Agents
Antirheumatic Agents