Time Required to Dissolve Urate Deposits

Официальное название

Time Required to Dissolve Urate Deposits in Patients With Gout

Обзор

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.

Подробное описание

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.

Вмешательства

• Диагностический тест Standard X-Rays
  \- Standard X-Rays: feet (Month 0)
• Диагностический тест Ultrasound
  \- 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.
• Диагностический тест DECT of feet
  DECT of feet: in tophaceous patients only (Month 0, Month 24)
• Биопрепарат DNA sample
  DNA will be collected at Month 0
• Биопрепарат Serum 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.

Первичные конечные точки

• Time required for complete dissolution of urate deposits [Срок оценки: Change between baseline (month 0) and up to 48 months after initiation of ULT]

Вторичные конечные точки (5)

• Number of flares [Срок оценки: At Month 0, Month 6, Month 12, Month 18, Month 24, Month 30, Month 36, Month 48]
• Health status as assessed by the EQ-5D-3L questionnaire [Срок оценки: At Month 0, Month 6, Month 12, Month 24, Month 36, Month 48]
• Patient self-rated health on a vertical visual analogue scale (EQ VAS) [Срок оценки: At Month 0, Month 6, Month 12, Month 24, Month 36, Month 48]
• Health status as assessed by the HAQ-ID questionnaire [Срок оценки: At Month 0, Month 6, Month 12, Month 24, Month 36, Month 48]
• Proteins profils [Срок оценки: Month 0, Month 6, Month 24, Month 36]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Франция · 1 центр

• APHP, Lariboisière Hospital, Rheumatology departement — Paris

Идентификаторы

NCT: NCT06669000 · APHP240644 · 2024-A00937-40

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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