The Orienting Study (ORIENTING)

March 25, 2026 updated by: I.R.C.C.S Ospedale Galeazzi-Sant'Ambrogio

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

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.

Study Overview

Status

Recruiting

Conditions

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.

Study Type

Observational

Enrollment (Estimated)

450

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Italy
    • Milano
      • Milan, Milano, Italy, 20157

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients affected by gout, CPPD or osteoarthritis.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Gout
Patients affected by gout according to ACR/EULAR classification criteria
CPPD
Patients affected by gout according to ACR/EULAR classification criteria
Disease control
Patients with a diagnosis of osteoarthritis according to ACR classification criteria

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Extent of CPP crystal deposition assessed by ultrasound over time
Time Frame: Baseline and every 6 months up to 10 years
Calcium pyrophosphate crystal deposition (CPPD) will be assessed using the OMERACT Ultrasound Scoring System for CPPD at patient level and at joint level. Each anatomical site will be graded on a semi-quantitative scale from 0 to 3. According to the clinical scenario and the clinician decision, patients will undergo an US examination of the affected joints. Case by case the following joints will be evaluated: shoulder, elbow, wrist, hand, hip, knee, ankle, Achilles tendon, foot. The total score will be calculated as the sum of scores across all evaluated sites and normalized by the number of sites assessed per patient. The measure will be assessed longitudinally to evaluate changes in crystal deposition over time.
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
Assessment of the extent of monosodium urate (MSU) crystal deposition Calcium pyrophosphate crystal deposition (CPPD) will be assessed using the OMERACT Ultrasound Scoring System for Gout Lesions (double contour sign, tophi, aggregates). Each lesion will be graded on a semi-quantitative scale from 0 to 3. A total score will be calculated by summing scores across all evaluated joints. According to the clinical scenario and the clinician decision, patients will undergo an US examination of the affected joints. Case by case the following joints will be evaluated: shoulder, elbow, wrist, hand, hip, knee, ankle, Achilles tendon, foot. The total score will be calculated as the sum of scores across all evaluated sites and normalized by the number of sites assessed per patient. The measure will be assessed longitudinally to evaluate changes in crystal deposition over time.
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
Bone erosions will be assessed using the OMERACT Ultrasound Scoring System for Bone Erosions. Each site will be graded from 0 to 3 and summed across all evaluated joints to obtain a total erosion score. The measure will be assessed longitudinally to evaluate changes over time.
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
Osteophytes will be assessed using the OMERACT Ultrasound Scoring System for Osteophytes. Each site will be graded from 0 to 3 and summed across all evaluated joints to obtain a total osteophyte score. The measure will be assessed longitudinally to evaluate changes over time.
Baseline and every 6 months up to 10 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ESR
Time Frame: From baseline every 6 months up to 10 years
Change From Baseline in Erythrocyte Sedimentation Rate (ESR mm/h) between patients with CPPD and gout and disease-controls with OA
From baseline every 6 months up to 10 years
CRP
Time Frame: From baseline every 6 months up to ten years
Change From Baseline in C-Reactive Protein (CRP mg/L) between CPPD and Gout patients and controls with OA
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
Synovitis will be evaluated thanks to Global OMERACT-EULAR Synovitis Score (GLOESS). Ultrasound evaluation will be performed on clinically relevant joints and anatomical structures as determined by the treating physician.
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
Tenosynovitis will be assessed using the OMERACT ultrasound scoring system on a semi-quantitative scale. Ultrasound evaluation will be performed on clinically relevant joints and anatomical structures as determined by the treating physician.
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
Joint effusion will be assessed using ultrasound on a semi-quantitative scale from 0 to 3. The joints to be evaluated will be selected according to the clinician's judgement
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
The number of tender joints will be assessed using the 68-joint count method.
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
The number of swollen joints will be assessed using the 66-joint count method.
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
Disease activity will be assessed by the physician using a visual analog scale (0-100)
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
Scale (0-100)
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
Scale (0-100)
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
Scale (0-100)
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
Score (0-3) for every item of the questionnaire, then the sum is calculated
From baseline every six months up to ten years
Cardiovascular Risk Assessed by SCORE2 and SCORE2-OP
Time Frame: At baseline and if clinically indicated during follow-up up to ten years
Cardiovascular risk will be estimated using SCORE2 and SCORE2-OP algorithms, depending on patient's age. Both scores express a percentage (%) of the 10-year risk.
At baseline and if clinically indicated during follow-up up to ten years
Incidence of Cardiovascular Events
Time Frame: During the 10 years follow up
Occurrence of cardiovascular events recorded during follow-up (Number of events / % of patients)
During the 10 years follow up
Distribution of Clinical Phenotypes of CPPD and Gout
Time Frame: Baseline
Phenotypes of calcium pyrophosphate deposition (CPPD) disease and gout will be classified according to established classification criteria (ACR/EULAR recommendations and G-CAN consensus respectively).
Baseline

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum suPAR Levels Assessed by Enzyme Immunoassay
Time Frame: Once during the 10 years follow up
Serum soluble urokinase plasminogen activator receptor (suPAR) levels will be measured using an ELISA-based assay on blood and/or synovial fluid, whenever the patients undergo arthrocentesis for other reasons
Once during the 10 years follow up
Intima media thickness at ultrasound of carothid arteries
Time Frame: As clinically indicated during follow-up up to ten years from baseline
Measurment of intima-media thickness (CMIT) at ultrasound of carothid arteries performed as part of routine care will be collected to assess increased atherosclerotic risk. The European Society of Cardiology (ESC) often highlights CMIT> 0.9 as a critical threshold to determine an increased risk
As clinically indicated during follow-up up to ten years from baseline
Assessment of joint damage using X-ray, CT or MRI
Time Frame: As clinically indicated during follow-up from baseline up to ten years
On radiographs and CT, osteoarthritis severity will be evaluated based on osteophytes, joint space narrowing, and subchondral bone changes, using a semi-quantitative grading scale (e.g., Kellgren-Lawrence grade 0-4 for radiographs). On MRI, joint damage will be assessed including cartilage integrity and other structural abnormalities using appropriate semi-quantitative scoring systems (WORMS, MOAKS)
As clinically indicated during follow-up from baseline up to ten years
Histological and Molecular Characteristics of Joint Tissues in Patients Undergoing Arthroplasty
Time Frame: At time of surgery (as applicable)
Biological samples (bone, cartilage, synovial membrane, ligaments/tendons, synovial fluid) collected during clinically indicated arthroplasty procedures will be analyzed using histology, immunohistochemistry, and Raman spectroscopy to assess tissue morphology, inflammatory features, and crystal deposition.
At time of surgery (as applicable)
Coronary stenosis at Coronary Computed Tomography Angiography (CCTA)
Time Frame: As clinically indicated during follow up up to ten years
The presence of coronary stenosis at Coronary Computed Tomography Angiography (CCTA) will be recorded. An obstructive stenosis occupies more than 50% of the lumen.
As clinically indicated during follow up up to ten years
Assessment of bone mineral density at DEXA
Time Frame: As clinically indicated from baseline up to ten years follow up
Bone mineral density (BMD) will be measured using dual-energy X-ray absorptiometry at the lumbar spine and proximal femur. Results will be expressed in g/cm², T-scores, and Z-scores. Bone status will be classified as normal, osteopenia, or osteoporosis according to World Health Organization criteria.
As clinically indicated from baseline up to ten years follow up
Evaluation of CPP crystal and MSU crystal deposition at X-ray, TC or MRI
Time Frame: As clinically indicated from baseline up to ten years follow up
CPP and MSU crystal deposition in articular or periarticular structures at other imaging modalities (X-rays, CT scans, MRI) will be qualitatively assessed and documented as presence/absence.
As clinically indicated from baseline up to ten years follow up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

I.R.C.C.S Ospedale Galeazzi-Sant'Ambrogio

Investigators

  • Principal Investigator: Georgios Filippou, MD, Università degli Studi di Milano / IRCCS Ospedale Galeazzi-Sant'Ambrogio

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 30, 2024

Primary Completion (Estimated)

October 30, 2027

Study Completion (Estimated)

October 30, 2039

Study Registration Dates

First Submitted

December 18, 2024

First Submitted That Met QC Criteria

March 25, 2026

First Posted (Actual)

March 31, 2026

Study Record Updates

Last Update Posted (Actual)

March 31, 2026

Last Update Submitted That Met QC Criteria

March 25, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ORIENTING L4181

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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