Bone Resorption, Osteoclastogenesis and Adalimumab
Information source: Université de Sherbrooke
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Rheumatoid Arthritis.
Intervention: Adalimumab (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: Université de Sherbrooke Official(s) and/or principal investigator(s): Artur Ferandnes, Principal Investigator, Affiliation: Centre de recherche Étienne Le-Bel at Centre hospitalier universitaire de Sherbrooke
Overall contact: Artur Fernandes, Phone: 819-346-1110, Ext: 15417, Email: Artur.Jose.De.B.Fernandes@USherbrooke.ca
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.
Clinical Details
Official title: Bone Resorption, Osteoclastogenesis and Adalimumab
Study design: Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science
Primary outcome: Verify if the treatment with Adalimumab may be associated with a reduction in the number of osteoclasts.
Secondary outcome: Verify if this reduction may be associated with a better response to the treatment.To verify reduction of osteoclasts may be associated with a better response to the treatment. To verify reduction of osteoclasts may be associated with a better response to the treatment.
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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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.
Locations and Contacts
Artur Fernandes, Phone: 819-346-1110, Ext: 15417, Email: Artur.Jose.De.B.Fernandes@USherbrooke.ca
CRC Étienne Le-Bel at CHUS, Sherbrooke, Quebec J1H 5N4, Canada; Recruiting Stéphanie Mcmahon, Phone: 819-346-1110, Ext: 12845 Maryse Berthiaume, Phone: 819-346-1110, Ext: 12891 Artur Fernandes, Principal Investigator
Additional Information
Starting date: May 2013
Last updated: December 2, 2014
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