Bone Resorption, Osteoclastogenesis and Adalimumab (BROCAII)
Primary Purpose
RheumatoId Arthritis
Status
Unknown status
Phase
Phase 4
Locations
Canada
Study Type
Interventional
Intervention
Adalimumab
Sponsored by
About this trial
This is an interventional basic science trial for RheumatoId Arthritis focused on measuring Rheumatoid Arthritis, Adalimumab, Humira
Eligibility 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.
Sites / Locations
- CRC Étienne Le-Bel at CHUSRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Adalimumab (humira)
Arm Description
As standard of care.
Outcomes
Primary Outcome Measures
Verify if the treatment with Adalimumab may be associated with a reduction in the number of osteoclasts.
By calculating the number of osteoclast and osteoblast in patient serum.
Secondary Outcome Measures
Verify if this reduction may be associated with a better response to the treatment.
Disease activity defined as a DAS28 score
To verify reduction of osteoclasts may be associated with a better response to the treatment.
Functional status by the HAQ
To verify reduction of osteoclasts may be associated with a better response to the treatment.
Radiological progression defined by Sharp scores
Full Information
NCT ID
NCT02035800
First Posted
December 10, 2013
Last Updated
May 7, 2018
Sponsor
Université de Sherbrooke
Collaborators
AbbVie
1. Study Identification
Unique Protocol Identification Number
NCT02035800
Brief Title
Bone Resorption, Osteoclastogenesis and Adalimumab
Acronym
BROCAII
Official Title
Bone Resorption, Osteoclastogenesis and Adalimumab
Study Type
Interventional
2. Study Status
Record Verification Date
May 2018
Overall Recruitment Status
Unknown status
Study Start Date
May 2013 (undefined)
Primary Completion Date
December 2018 (Anticipated)
Study Completion Date
December 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Université de Sherbrooke
Collaborators
AbbVie
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
RheumatoId Arthritis
Keywords
Rheumatoid Arthritis, Adalimumab, Humira
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
120 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Adalimumab (humira)
Arm Type
Experimental
Arm Description
As standard of care.
Intervention Type
Drug
Intervention Name(s)
Adalimumab
Other Intervention Name(s)
Humira
Intervention Description
Patient will received medication as standard of care
Primary Outcome Measure Information:
Title
Verify if the treatment with Adalimumab may be associated with a reduction in the number of osteoclasts.
Description
By calculating the number of osteoclast and osteoblast in patient serum.
Time Frame
6 months after treatment
Secondary Outcome Measure Information:
Title
Verify if this reduction may be associated with a better response to the treatment.
Description
Disease activity defined as a DAS28 score
Time Frame
6 months after treatment
Title
To verify reduction of osteoclasts may be associated with a better response to the treatment.
Description
Functional status by the HAQ
Time Frame
6 months after treatment
Title
To verify reduction of osteoclasts may be associated with a better response to the treatment.
Description
Radiological progression defined by Sharp scores
Time Frame
6 months after traitment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Artur Fernandes
Phone
819-346-1110
Ext
15417
Email
Artur.Jose.De.B.Fernandes@USherbrooke.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Gilles Boire
Phone
819-346-1110
Ext
15063
Email
Gilles.Boire@usherbrooke.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Artur Ferandnes
Organizational Affiliation
Centre de recherche Étienne Le-Bel at Centre hospitalier universitaire de Sherbrooke
Official's Role
Principal Investigator
Facility Information:
Facility Name
CRC Étienne Le-Bel at CHUS
City
Sherbrooke
State/Province
Quebec
ZIP/Postal Code
J1H 5N4
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stéphanie Mcmahon
Phone
819-346-1110
Ext
12845
First Name & Middle Initial & Last Name & Degree
Maryse Berthiaume
Phone
819-346-1110
Ext
12891
First Name & Middle Initial & Last Name & Degree
Artur Fernandes
12. IPD Sharing Statement
Learn more about this trial
Bone Resorption, Osteoclastogenesis and Adalimumab
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