Clinical trial NCT02035800: Bone Resorption, Osteoclastogenesis and Adalimumab
Official title: Bone Resorption, Osteoclastogenesis and Adalimumab
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: RheumatoId Arthritis
Keywords: Rheumatoid Arthritis
Adalimumab
Humira
Lead sponsor: Université de Sherbrooke
Sponsor class: OTHER
Collaborators: name: AbbVie
First posted: 2014-01-14
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

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.

Primary outcomes:
measure: Verify if the treatment with Adalimumab may be associated with a reduction in the number of osteoclasts.
timeFrame: 6 months after treatment
Secondary outcomes:
measure: Verify if this reduction may be associated with a better response to the treatment.
timeFrame: 6 months after treatment
measure: To verify reduction of osteoclasts may be associated with a better response to the treatment.
timeFrame: 6 months after treatment
measure: To verify reduction of osteoclasts may be associated with a better response to the treatment.
timeFrame: 6 months after traitment
Other outcomes:
Locations:
city: Sherbrooke
country: Canada
facility: CRC Étienne Le-Bel at CHUS
state: Quebec
Study officials:
affiliation: Centre de recherche Étienne Le-Bel at Centre hospitalier universitaire de Sherbrooke
name: Artur Ferandnes
role: PRINCIPAL_INVESTIGATOR
References: