RheumatoId ArthritisPhase 4BROCAIINCT02035800
Bone Resorption, Osteoclastogenesis and Adalimumab
A Phase 4 study testing Adalimumab in people with RheumatoId Arthritis, run by Université de Sherbrooke at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- RheumatoId Arthritis
- What is being tested?
- Adalimumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteCanada
- Study dates
- May 2013to Dec 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Canada1 site, 1 recruiting
- Recruiting
CRC Étienne Le-Bel at CHUS
Sherbrooke, Quebec, J1H 5N4
Stéphanie Mcmahon, 819-346-1110 ext. 12845
Maryse Berthiaume, 819-346-1110 ext. 12891
About this study
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.
Read the 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.
- Conditions
- RheumatoId Arthritis
- Being tested
- Adalimumab
- Keywords
- Rheumatoid Arthritis, Adalimumab, Humira
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AdalimumabDrug
Also called Humira
Patient will received medication as standard of care
| Study group | Role | What they receive |
|---|---|---|
| Adalimumab (humira) | Experimental | As standard of care. Receives: Drug: Adalimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months after treatment
Secondary outcomes (3)
Verify if this reduction may be associated with a better response to the treatment.
Disease activity defined as a DAS28 score
Measured: 6 months after treatment
To verify reduction of osteoclasts may be associated with a better response to the treatment.
Functional status by the HAQ
Measured: 6 months after treatment
To verify reduction of osteoclasts may be associated with a better response to the treatment.
Radiological progression defined by Sharp scores
Measured: 6 months after traitment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2014 (estimated)
- Study startMay 2013
- Primary completionDec 2018 (estimated)
- Study completionDec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for RheumatoId ArthritisStudies of the same condition, open and under way.
- More trials run by Université de SherbrookeThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Université de Sherbrooke
- Sponsor type
- University, hospital or other
- Collaborators
- AbbVie
- Responsible party
- Sponsor
- Investigators
- Artur Ferandnes, Principal investigator, Centre de recherche Étienne Le-Bel at Centre hospitalier universitaire de Sherbrooke
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02035800
- Sponsor's protocol ID
- IMM 11-0163
- Acronym
- BROCAII
- Status last verified
- May 2018
- First submitted
- 10 Dec 2013
- Last updated
- 8 May 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bone Resorption, Osteoclastogenesis and Adalimumab
- ClinicalTrials.gov ID
- NCT02035800
- Acronym / sponsor ID
- BROCAII / IMM 11-0163
- Conditions
- RheumatoId Arthritis
- Keywords
- Rheumatoid Arthritis, Adalimumab, Humira
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Université de SherbrookeUniversity, hospital or other
- Collaborators
- AbbVie
- Study start
- May 2013
- Primary completion
- Dec 2018 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 14 Jan 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Adalimumab (humira) | Experimental | Drug: AdalimumabAs standard of care. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (2 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AdalimumabAlso: HumiraPatient will received medication as standard of care | Drug | Adalimumab (humira) |
Primary outcome
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.
3 secondary outcomes
Verify if this reduction may be associated with a better response to the treatment.
Time frame: 6 months after treatment
To verify reduction of osteoclasts may be associated with a better response to the treatment.
Time frame: 6 months after treatment
To verify reduction of osteoclasts may be associated with a better response to the treatment.
Time frame: 6 months after traitment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Artur Ferandnes principal investigator
Centre de recherche Étienne Le-Bel at Centre hospitalier universitaire de Sherbrooke
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Adalimumab in people with RheumatoId Arthritis, run by Université de Sherbrooke at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Artur Fernandes (819-346-1110 ext. 15417, Artur.Jose.De.B.Fernandes@USherbrooke.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Verify if the treatment with Adalimumab may be associated with a reduction in the number of osteoclasts. (time frame: 6 months after treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2018.