Clinical trial NCT03555240: Regional Registry-based Biobank Development and Pharmacogenetic Analysis in Rheumatoid Arthritis
Official title: Regional Registry-based Biobank Development and Pharmacogenetic Analysis: Synergistic Strategies Driving Towards Personalized Medicine in Rheumatoid Arthritis Management
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis
Lead sponsor: Istituto Ortopedico Rizzoli
Sponsor class: OTHER
Collaborators: name: Regione Emilia Romagna - Italy within PRU-Liberati project
First posted: 2018-06-13
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patient with residents in Emilia Romagna Region, partecipating to the regional rheumatoid arthritis registy

Brief summary: Aim of this project is the building-up of an integrated model of multidisciplinary research tools to support large-scale and high-quality disease-based studies.

Detailed description: Biologics have revolutionized rheumatoid arthritis (RA) management, with a great impact on patient that justifies treatment with these high-cost drugs. Nevertheless, timing and proper therapeutic decision making remain the main challenge in clinical practice.

Pharmacogenetics approach might open promising perspectives, increasing our understanding on genetic-related drug efficacy. Nevertheless, to ensure feasibility and reliability of translational applications of this strategy in clinical practice, large population-based research studies represent a crucial key step.

Objectives

Major aim of this project is the building-up of an integrated model of multidisciplinary research tools to support large-scale and high-quality disease-based studies. The main targets of this proposal will be:

* to develop a disease-based biobank, integrated with already established Emilia-Romagna regional RA Registry, providing a large-scale prospective collection and storing of multiple biological samples
* to perform a pharmacogenetic study analyzing a panel of gene variants potentially influencing the response to Tumor Necrosis Factor (TNF) blockers. Methods
* Biobank development. A step-wise plan will be considered for: designing biobank governance frame-work, defining Standard Operating Procedures, implementing information system resources. All these procedures will be applied for collecting, processing and storing biological samples of patients included in regional RA registry.
* Pharmacogenetic study. A panel of candidate gene variants will be studied in genomic DNA from 300 patients enrolled in the regional RA registry. The association between genotypes and response to biological drugs will be assessed by data-mining approach, and a predictive model will be defined. Expected Results This proposal will create a disease-based biobank, tightly integrated with the already established Emilia-Romagna regional RA Registry, and pave the way towards personalized therapy applications in Rheumatology.

Eligibility criteria: Inclusion Criteria:

1. Diagnosis of Arthritis Rheumatoid according American College of Rheumatology (ACR)1987 or according ACR/European League Against Rheumatism (EULAR) 2010 criteria
2. Patients with new diagnosis or patients already diagnosed with active disease \[with Disease Activity Score (DAS) 28 \> o = 4,2\] or patients switching therapy
3. Male and female patients of minimum 18 years old
4. Provision of informed consent

Exclusion Criteria:

1) Patients living outside Emilia Romagna region

Primary outcomes:
measure: Biobank creation
timeFrame: through study completion, an average of 5 years
Secondary outcomes:
measure: Identification of genes potentially predictive of response to biological drugs
timeFrame: at 12 Months
Other outcomes:
Locations:
city: Bologna
country: Italy
facility: Rheumatology Unit IRCCS Orthopedic Rizzoli Institute
state: BO
city: Bologna
country: Italy
facility: Rheumatology Unit, Internal Medicine Department of Internal Medicine and Nephrology diseases and Aging
state: BO
city: Cesena
country: Italy
facility: Rheumatology Unit, Department of Internal Medicine Buflini Hospital
state: FC
city: Ferrara
country: Italy
facility: Medical Genetics Unit, Dept. of Biomedical and Specialty Surgery
state: FE
city: Ferrara
country: Italy
facility: Rheumatology Unit S.Anna University Hospital
state: FE
city: Forlì
country: Italy
facility: Rheumatology Unit, Internal Medicine Department Morgagni Hospital
state: Fo
city: Ravenna
country: Italy
facility: Unit of Internal Medicine, Medical Internistic Department Ospedale Santa maria delle croci
state: RA
city: Reggio Emilia
country: Italy
facility: Division of Rheumatology Azienda Ospedaliera-IRCC S, Reggio Emilia
state: RE
city: Rimini
country: Italy
facility: Department of Internal Medicine Infermis' Hospital
state: RN
city: Bologna
country: Italy
facility: Laboratory of Immunorheumatology and Tissue Regeneration IRCC Rizzoli Orthopedic Institute
Study officials:
affiliation: Rizzoli Orthopedic Institute
name: Elisa Assirelli, BSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Boonen A, Severens JL. The burden of illness of rheumatoid arthritis. Clin Rheumatol. 2011 Mar;30 Suppl 1:S3-8. doi: 10.1007/s10067-010-1634-9. Epub 2011 Feb 26.
citation: Hamilton SR, Chatrian GE, Mills RP, Kalina RE, Bird TD. Cone dysfunction in a subgroup of patients with autosomal dominant cerebellar ataxia. Arch Ophthalmol. 1990 Apr;108(4):551-6. doi: 10.1001/archopht.1990.01070060099057.
citation: Scott DL. Biologics-based therapy for the treatment of rheumatoid arthritis. Clin Pharmacol Ther. 2012 Jan;91(1):30-43. doi: 10.1038/clpt.2011.278. Epub 2011 Dec 14.
citation: Ruderman EM. Overview of safety of non-biologic and biologic DMARDs. Rheumatology (Oxford). 2012 Dec;51 Suppl 6:vi37-43. doi: 10.1093/rheumatology/kes283.
citation: Prajapati R, Plant D, Barton A. Genetic and genomic predictors of anti-TNF response. Pharmacogenomics. 2011 Nov;12(11):1571-85. doi: 10.2217/pgs.11.114.