The Orienting Study

Official title

The Natural History Of Calcium Pyrophosphate Deposition And Gout: An Observational Clinical And Imaging Study - The Orienting Study

Overview

This study at IRCCS Galeazzi - Sant'Ambrogio Hospital involves patients with gout, CPPD, and osteoarthritis as a control group. Patients will receive routine care with regular clinical, laboratory, and imaging assessments every six months, alongside urgent visits as needed. The study aims to understand crystal deposits in joints and blood vessels and monitor their progression over time, assessing how these deposits respond to standard treatments and if they are associated with cardiovascular complications. Data will be collected from medical records over a follow-up period of up to 10 years, offering long-term insights into disease impact and treatment effectiveness.

Detailed description

This is a monocentric observational longitudinal study in which patients diagnosed with gout or CPPD and disease-controls with OA will be consecutively recruited from the outpatient clinics of the Rheumatology and Orthopaedic Hip Departments of the IRCCS Galeazzi - Sant'Ambrogio Hospital.

The investigators will enroll consecutive patients with CPPD and gout and disease-controls with OA fulfilling the inclusion and exclusion criteria, from the outpatient clinics of the Rheumatology Department and Orthopaedic Hip Department of the IRCCS Galeazzi - Sant'Ambrogio Hospital, who will be seen for routine or urgent gout/CPPD/OA care following local scheduling processes, without applying any further selection criteria. All patients, in line with clinical routine practice, will undergo a standard clinical, laboratory and imaging assessment, both at baseline and during scheduled follow-up visits (every 6 months) and urgent follow-up visits, tailored to each patient's needs. The study comprises two phases. The first, aims to evaluate the extent of crystal deposition in joints and in blood vessels in patients with CPPD and gout. The second, focuses on monitoring the extension of crystals deposits, their associations with conventional therapies, and evaluating the development of cardiovascular complications in patients with CPPD and gout in comparison to disease-controls with OA. The data for the study will be retrieved from the medical records of the patients and recorded into an appositely created electronic case report form (CRF). The enrollment period will last 3 years (starting from the time of approval of the study), and the follow up period will last 10 years.

Primary outcome measures

• Extent of CPP crystal deposition assessed by ultrasound over time [Time frame: Baseline and every 6 months up to 10 years]
• Extent of MSU crystal deposition assessed by ultrasound over time [Time frame: Baseline and every 6 months up to 10 years]
• Progression of bone erosions assessed by ultrasound [Time frame: Baseline and every 6 months up to 10 years]
• Progression of osteophites assessed by ultrasound [Time frame: Baseline and every 6 months up to 10 years]

Secondary outcome measures (12)

• ESR [Time frame: From baseline every 6 months up to 10 years]
• CRP [Time frame: From baseline every 6 months up to ten years]
• Synovitis Score Assessed by Global OMERACT-EULAR Synovitis Score (GLOESS) [Time frame: Baseline and every 6 months up to 10 years]
• Tenosynovitis Score Assessed by OMERACT Ultrasound Scoring System [Time frame: Baseline and every 6 months up to 10 years]
• Joint Effusion Score Assessed by Ultrasound [Time frame: Baseline and every 6 months up to 10 years]
• Number of Tender Joints Assessed Using 68-Joint Count [Time frame: Baseline and every 6 months up to 10 years]
• Number of Swollen Joints Assessed Using 66-Joint Count [Time frame: Baseline and every 6 months up to 10 years]
• Physician Global Assessment of Disease Activity [Time frame: Baseline and every 6 months up to 10 years]
• Patient Global Assessment of Disease Activity [Time frame: Baseline and every 6 months up to 10 years]
• Patient-Reported Pain Assessed by Visual Analog Scale (VAS) [Time frame: Baseline and every 6 months up to 10 years]
• Patient-Reported Global Health Status [Time frame: Baseline and every 6 months up to 10 years]
• Functional Disability Assessed by Health Assessment Questionnaire (HAQ) [Time frame: From baseline every six months up to ten years]

Eligibility criteria

The inclusion criteria for CPPD patients are:

• Patients diagnosed with CPPD disease according to the ACR/EULAR 2023 classification criteria.
• Patients with evidence of asymptomatic CPPD on US or X-rays (not meeting the classification criteria) according to validated imaging definitions.
• Aged older than 18 years.
• Able to provide informed consent, according to requirements of local IRB/ethics committee.

The inclusion criteria for gout patients are:

• Patients diagnosed with gout according to the ACR/EULAR 2015 classification criteria.
• Aged older than 18 years.
• Able to provide informed consent, according to requirements of local IRB/ethics committee.

The inclusion criteria for disease controls are:

• A diagnosis of OA according to ACR classification criteria
• No evidence of uric acid or calcium pyrophosphate deposits on US
• Uric acid < 6 mg/dL
• Aged older than 18 years.
• Able to provide informed consent, according to requirements of local IRB/ethics committee

The exclusion criteria for gout/CPPD patients are:

• Known history of other inflammatory arthropathies
• Unable to provide informed consent, according to requirements of local IRB/ethics committee.

The exclusion criteria for disease controls are:

• Known history of other inflammatory arthropathies
• Unable to provide informed consent, according to requirements of local IRB/ethics committee.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Italy · 1 center

• IRCCS Ospedale Galeazzi-Sant'Ambrogio — Milan

Publications

• Moller I, Janta I, Backhaus M, Ohrndorf S, Bong DA, Martinoli C, Filippucci E, Sconfienza LM, Terslev L, Damjanov N, Hammer HB, Sudol-Szopinska I, Grassi W, Balint P, Bruyn GAW, D'Agostino MA, Hollander D, Siddle HJ, Supp G, Schmidt WA, Iagnocco A, Koski J, Kane D, Fodor D, Bruns A, Mandl P, Kaeley GS, Micu M, Ho C, Vlad V, Chavez-Lopez M, Filippou G, Ceron CE, Nestorova R, Quintero M, Wakefield R PMID 28814430
• Hammer HB, Iagnocco A, Mathiessen A, Filippucci E, Gandjbakhch F, Kortekaas MC, Moller I, Naredo E, Wakefield RJ, Aegerter P, D'Agostino MA. Global ultrasound assessment of structural lesions in osteoarthritis: a reliability study by the OMERACT ultrasonography group on scoring cartilage and osteophytes in finger joints. Ann Rheum Dis. 2016 Feb;75(2):402-7. doi: 10.1136/annrheumdis-2014-206289. Ep PMID 25520476
• Naredo E, D'Agostino MA, Wakefield RJ, Moller I, Balint PV, Filippucci E, Iagnocco A, Karim Z, Terslev L, Bong DA, Garrido J, Martinez-Hernandez D, Bruyn GA; OMERACT Ultrasound Task Force*. Reliability of a consensus-based ultrasound score for tenosynovitis in rheumatoid arthritis. Ann Rheum Dis. 2013 Aug;72(8):1328-34. doi: 10.1136/annrheumdis-2012-202092. Epub 2012 Sep 14. PMID 22984169
• Horta-Baas G. Patient-Reported Outcomes in Rheumatoid Arthritis: A Key Consideration for Evaluating Biosimilar Uptake? Patient Relat Outcome Meas. 2022 Mar 30;13:79-95. doi: 10.2147/PROM.S256715. eCollection 2022. PMID 35388274
• Duarte-Garcia A, Leung YY, Coates LC, Beaton D, Christensen R, Craig ET, de Wit M, Eder L, Fallon L, FitzGerald O, Gladman DD, Goel N, Holland R, Lindsay C, Maxwell L, Mease P, Orbai AM, Shea B, Strand V, Veale DJ, Tillett W, Ogdie A. Endorsement of the 66/68 Joint Count for the Measurement of Musculoskeletal Disease Activity: OMERACT 2018 Psoriatic Arthritis Workshop Report. J Rheumatol. 2019 Aug PMID 30770518
• Altman R, Alarcon G, Appelrouth D, Bloch D, Borenstein D, Brandt K, Brown C, Cooke TD, Daniel W, Gray R, et al. The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hand. Arthritis Rheum. 1990 Nov;33(11):1601-10. doi: 10.1002/art.1780331101. PMID 2242058
• Altman R, Alarcon G, Appelrouth D, Bloch D, Borenstein D, Brandt K, Brown C, Cooke TD, Daniel W, Feldman D, et al. The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hip. Arthritis Rheum. 1991 May;34(5):505-14. doi: 10.1002/art.1780340502. PMID 2025304
• Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, Christy W, Cooke TD, Greenwald R, Hochberg M, et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum. 1986 Aug;29(8):1039-49. doi: 10.1002/art.1780290816. PMID 3741515

Identifiers

NCT: NCT07504146 · ORIENTING L4181

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗