Clinical trial NCT06669000: Time Required to Dissolve Urate Deposits
Official title: Time Required to Dissolve Urate Deposits in Patients with Gout
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Gout
Keywords: Gout
Flares
Tophi
Urate levels
Urate deposits
Ultrasound
Allopurinol
Febuxostat
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Institut National de la Santé Et de la Recherche Médicale, France
name: ART VIGGO Association for Research
First posted: 2024-11-01
Enrollment: 250
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: Gout patient managed according to a T2T (treat to target) strategy

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.

Eligibility criteria: 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

Primary outcomes:
measure: Time required for complete dissolution of urate deposits
timeFrame: Change between baseline (month 0) and up to 48 months after initiation of ULT
Secondary outcomes:
measure: Number of flares
timeFrame: At Month 0, Month 6, Month 12, Month 18, Month 24, Month 30, Month 36, Month 48
measure: Health status as assessed by the EQ-5D-3L questionnaire
timeFrame: At Month 0, Month 6, Month 12, Month 24, Month 36, Month 48
measure: Patient self-rated health on a vertical visual analogue scale (EQ VAS)
timeFrame: At Month 0, Month 6, Month 12, Month 24, Month 36, Month 48
measure: Health status as assessed by the HAQ-ID questionnaire
timeFrame: At Month 0, Month 6, Month 12, Month 24, Month 36, Month 48
measure: Proteins profils
timeFrame: Month 0, Month 6, Month 24, Month 36
Other outcomes:
Locations:
city: Paris
country: France
facility: APHP, Lariboisière Hospital, Rheumatology departement
Study officials:
References: