Gout
Conditions
Keywords
Gout, Flares, Tophi, Urate levels, Urate deposits, Ultrasound, Allopurinol, Febuxostat
Brief summary
Gout is characterized by episodes of acute arthritis of the lower limbs due to intermittent activation of innate immunity in the joints where urate crystals have formed. These crystals occur when serum urate (SUA) levels have been above 70 mg/L for many years. They can be dissolved by lowering SUA levels to at least 60 mg/L (treat-to-target - T2T - strategy). Once the crystals are dissolved, patients are no longer symptomatic and are considered to be in remission (treat-to-dissolve - T2D - strategy). The presence of crystals and their dissolution during treatment can be monitored by repeated ultrasound (US) scans of the feet and knees. The time required for complete dissolution varies from patient to patient. ReViGore40 is a cohort designed to i) determine the time to complete dissolution of urate deposits in joints when SUA levels are maintained below 40 mg/L, ii) determine the factors (clinical, biological, genetic) associated with the time required for complete dissolution of urate deposits within joints.
Detailed description
Patients with newly diagnosed gout according to the 2015 ACR/Eular criteria, not treated with urate-lowering therapy and with US evidence of urate deposition (feet, knees; ultrasound score ≥ 2/24) will be enrolled in the ReViGore40 cohort. In all patients, SUA levels will be lowered with allopurinol or febuxostat (XOI) depending on renal function (eGFR greater or less than 30 ml/mn/m2) or uricosurics, by starting medications at a low dose and subsequent titration. The target SUA levels is less than 40 mg/L in all patients. Patients will then be monitored by US every 6 months until complete urate crystals dissolution. An ultrasound score (min 0- max 24; 0 meaning no urate deposits and 24 the highest value for quantifying the extent of deposits) will be calculated for each US scan. Dissolution is considered to have been achieved when a score of 0/24 is reached on two successive US scans performed 6 months apart. The Predictive Factors (clinical, biological, genetic) associated with the complete dissolution of urate deposits will be determined. DECT (feet) will be performed only in tophaceous patients at M0 and M24. Each patient will receive a capillary urate point of care device for self-urate measurement. Patients will be contacted monthly by nurses for the first 6 months to ensure treatment compliance and SUA target attainment. Blood samples will be collected at M0, M6, M24 and M36 for omic and epigenetic studies. Clinical data will be collected at M0, M6, M12, M24, M36 and M48. Change in Protein, Epigenetic and omic profils will be determined. DNA for genetic studies will be collected at M0. Co-morbidities, particularly cardiovascular and hepatic, will be assessed at M6: coronary artery calcium (CAC) scoring and liver fibroscan.
Interventions
DIAGNOSTIC_TESTStandard X-Rays
\- Standard X-Rays: feet (Month 0)
DIAGNOSTIC_TESTUltrasound
\- Ultrasound (score 0-24): assessment for DC (Double Contour) sign (0-3), aggregates (0-3), tophi (0-3) at MTP1s (first metatarsophalangeal joints) and DC sign (0-3) at both knees, according to the OMERACT, every 6 months until complete dissolution of urate deposits.
DIAGNOSTIC_TESTDECT of feet
DECT of feet: in tophaceous patients only (Month 0, Month 24)
BIOLOGICALDNA sample
DNA will be collected at Month 0
BIOLOGICALSerum collection
\- Serum will be collected at Month 0, Month 6, Month 12, Month 18, Month 24 , Month 36 and Month 48. For OMICs and epigenetic studies: Month 0, Month 6, Month 24 and Month 36.
Sponsors
Assistance Publique - Hôpitaux de Paris
Institut National de la Santé Et de la Recherche Médicale, France
ART VIGGO Association for Research
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age over 18 years * Gout according to the ACR/Eular 2015 criteria * SUA levels greater than 60 mg/L * US score (MTP1s, knees) ≥2/24 * Informed consent Dated and signed voluntarily
Exclusion criteria
* Ongoing urate lowering therapy * Severe and uncontrolled diseases such as cancer, cardiovascular or neurovegetative diseases * Pregnant or breast-feeding women * No affiliation to the French National Social Security System
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time required for complete dissolution of urate deposits | Change between baseline (month 0) and up to 48 months after initiation of ULT | For each patient, urate deposit dissolution will be monitored by repeated US scans. The US features which will be recorded according to the Outcome Measures in Rheumatology (OMERACT) scoring system: * at MTP1s: the DC sign, tophi and aggregates * at the knees (femoral condyles): the DC sign. The aggregates will only be scored if the DC sign and/or tophus are present and if the aggregates are not located inside a tophus. For each site, the US features will be graded as follows: absent (0) possible (1) moderate (2) important (3). Thus, a score (0-24) will be calculated for each patient. A score of 0 means that there are no longer urate deposits, while a score of 24 means that there are a lot of urate deposits. Dissolution is considered to have been achieved when a score of 0/24 is reached on two successive US scans performed 6 months apart |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of flares | At Month 0, Month 6, Month 12, Month 18, Month 24, Month 30, Month 36, Month 48 | Flares is defined when 3 of the following 4 criteria are present: * Patient-defined flare * Pain at rest greater than 3 on a 0-10 point numerical rating scale. * Presence of at least one swollen joint. * Presence of at least one hot joint. |
| Health status as assessed by the EQ-5D-3L questionnaire | At Month 0, Month 6, Month 12, Month 24, Month 36, Month 48 | Health status as assessed by the EQ-5D-3L descriptive system comprising the following five dimensions: * Mobility, * Self-care, * Usual activities, * Pain/discomfort * Anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. The patient is asked to indicate his/her health state by ticking the most appropriate box. This decision results into a 1-digit number. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. |
| Patient self-rated health on a vertical visual analogue scale (EQ VAS) | At Month 0, Month 6, Month 12, Month 24, Month 36, Month 48 | The EQ VAS records the patient's self-rated health on a vertical visual analogue scale from 0 to 100, with 100 being the best health and 0 corresponding to the worst health. |
| Health status as assessed by the HAQ-ID questionnaire | At Month 0, Month 6, Month 12, Month 24, Month 36, Month 48 | The questionnaire includes 8 sections: dressing, arising, eating, walking, hygiene, reach, grip, and activities, with 4 questions for each section. Scoring within each section is from 0 (without any difficulty) to 3 (unable to do). For each section the score given to that section is the worst score within the section. The 8 scores of the 8 sections are summed and divided by 8. The score obtained ranges from 0 to 3. The higher the score, the worse the state of health. |
| Proteins profils | Month 0, Month 6, Month 24, Month 36 | Change in plasma Proteins concentrations |
Countries
France
Contacts
CONTACTPascal RICHETTE, PR
Outcome results
None listed