Genetic of Chronic Kidney Disease and Gout in New Caledonia

Gout Clinical Trial

— CALEDGOUTCKD  

Official title:

Genetic of Chronic Kidney Disease and Gout : Analysis of Melanesian Families From New Caledonia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05607797
• Other study ID #: RC-P00116
• Status: Recruiting
• Phase: N/A
• Start date: March 14, 2023
• Est. completion date: August 31, 2024

Study information

• Verified date: March 2024
• Source: Lille Catholic University
• Contact: Marie DE SOLERE
• Phone: 03 20 22 59 31
• Email: desolere.marie[@]ghicl.net
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this research is to study the associations of genetic variants of gout and kidney failure, which are very common in the Melanesian population in New Caledonia

Description:

Gout is a chronic pathology linked to the deposition in the tissues of monosodium urate (MSU) crystals, secondary to hyperuricemia (high blood levels of urate). Gout causes very painful joint attacks that are first acute and then lead to chronic pain, and disabling deforming manifestations called tophus. The disease is strongly associated with cardiovascular comorbidities and chronic renal failure.

In New Caledonia, the prevalence of chronic kidney disease (CKD) (according to the glomerular filtration rate (GFR) < 60 ml/min) was of 7.4% in 2015 (according to the epidemiological study "Barometer Health 2015"). In the Loyalty Islands, which has overall significantly more Melanesian population, a local database showed that in 2018 the prevalence of patients having at least one blood test reporting kidney disease (GFR CKD< 60 ml/min) and seen at least once in the previous two years was as follows:

• 7.7% in Lifou (9,200 inhabitants)

• 8.4% in Maré (5,700 inhabitants)

• 9.1% in Ouvéa (3,400 inhabitants) In summary, inflammatory diseases such as CKD and gout have high prevalence in New Caledonia and the Loyalty Islands, and constitute a major health issue. Although the high prevalence of these diseases is probably due in part to non-genetic factors (environment, diet, etc.), it is likely, given the demographic history of this region, that undetected genetic risk alleles among the Melanesian population contribute to the appearance and progression of diseases. Performing genetic and epidemiological studies in an as yet understudied region is essential to identify these variants, which could lead to improved diagnoses and health outcomes.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2000
• Est. completion date: August 31, 2024
• Est. primary completion date: August 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

Criteria common to the 3 cohorts :

• Consenting to participate in the study and having signed the informed consent

• Claiming to be of Melanesian ethnicity

1. Patients with gout :

• Age: 18 - 70 years old

• To be included in the study, a patient with a diagnosis of gout in his medical file or declaring to have gout will have to satisfy to the ACR/EULAR (ref) classification criteria :

1. have had at least one episode of swelling, pain spontaneous, or triggered by pressure, of a joint peripheral or a bursa AND evidence of sodium urate crystals in a joint or bursitis symptomatic or by puncture of a tophus reported in his medical file.

2. Or Score > or =8 according to ACR/EULAR clinical criteria

2. Patients with CKD

• Age: 18 - 70 years old

• Patients on dialysis or CKD clinically diagnosed on the basis of:

1. Markers of kidney damage (one or more) : Albuminuria (ACR = 30 mg/g), Urinary sediment abnormalities (e.g., casts urinary), Electrolyte abnormalities and other, abnormalities due to tubular disorders (eg, hyperkalemia), abnormalities detected by histology, structural abnormalities detected by imaging (e.g.,USG), history of kidney transplantation

2. Decreased kidney function: GFR < 60 ml/min/1.73 m² (calculated according to the Chronic Kidney Disease - EPIdemiology formula: CKD-EPI)

3. Controls cohort

• Absence of gout or CKD

• Age: 30 - 80 years old

Exclusion Criteria:

• Pregnant women

• Individuals under guardianship / curatorship / judicially incapacitated

Related Conditions & MeSH terms

• Gout
• Kidney Diseases
• Renal Insufficiency
• Renal Insufficiency, Chronic

Intervention

Other:
• Epidemiological study
Sociodemographic data collection, treatments collection, physical assessment, clinical examination and physical and biological measurements, biological evaluation (blood and urine samples), CKD-specific clinical features collection, gout-specific clinical features collection, clinical characteristics specific to chronic diseases, questionnaires (Health Assessment Questionnaire (HAQ-II), EuroQol (EQ)-5D-5L, joint pain, state of health, diet and physical activity, access to care, addictions, pain scale (EVA), personal and family history)

Locations

Country	Name	City	State
New Caledonia	Medical Center of Wé (Lifou Island)	Nouméa

Sponsors (2)

Lead Sponsor	Collaborator
Lille Catholic University	Variant Bio, Inc.

Country where clinical trial is conducted

New Caledonia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Genome-wide association study (GWAS) in gout	GWAS is a research approach used to identify genomic variants that are statistically associated with a risk for a disease or a particular trait. The method involves surveying the genomes of many people, looking for genomic variants that occur more frequently in those with a specific disease or trait compared to those without the disease or trait. Once such genomic variants are identified, they are typically used to search for nearby variants that contribute directly to the disease or trait.	8 months
Primary	Phenome-wide association studies (PheWAS) in gout	PheWAS will be used to analyze many phenotypes compared to a single genetic variant (or other attribute).	8 months
Primary	GWAS in CKD	Genome-wide association study (GWAS) and Phenome-wide association studies (PheWAS) will be used. GWAS is a research approach used to identify genomic variants that are statistically associated with a risk for a disease or a particular trait. The method involves surveying the genomes of many people, looking for genomic variants that occur more frequently in those with a specific disease or trait compared to those without the disease or trait. Once such genomic variants are identified, they are typically used to search for nearby variants that contribute directly to the disease or trait. PheWAS will be used to analyze many phenotypes compared to a single genetic variant (or other attribute).	8 months
Primary	PheWAS in CKD	PheWAS will be used to analyze many phenotypes compared to a single genetic variant (or other attribute).	8 months
Secondary	Metabolomic profile in gout	Metabolomics profiling will be conducted using ultrahigh-performance liquid chromatography-tandem mass-spectrometry by the metabolomics provider Metabolon Inc. (USA) on fasting serum samples from participants. The metabolomic dataset measured by Metabolon includes known metabolites containing the following broad categories - amino-acids, peptides, carbohydrates, energy intermediates, lipids, nucleotides, cofactors and vitamins, and xenobiotics.	8 months
Secondary	Metabolomic profile in CKD	Metabolomics profiling will be conducted using ultrahigh-performance liquid chromatography-tandem mass-spectrometry by the metabolomics provider Metabolon Inc. ( USA) on fasting serum samples from participants. The metabolomic dataset measured by Metabolon includes known metabolites containing the following broad categories - amino-acids, peptides, carbohydrates, energy intermediates, lipids, nucleotides, cofactors and vitamins, and xenobiotics.	8 months
Secondary	GWAS and severity of CKD according to glomerular filtration rate (GFR)	GWAS will be used to identify genomic variants that are statistically associated with severity. Stage of severity according to GFR (mL/min/1.73m2): Mild renal impairment with normal or increased filtration : Over 90; Mild decrease in renal function : 60-89; Moderate decrease in renal function : 30-59; Severe decrease in renal function : 15-29; Renal failure: Less than 15 (or dialysis)	8 months
Secondary	GWAS and severity of gout	GWAS will be used to identify genomic variants that are statistically associated with severity.; Severity will be defined using four binary variables: number of attacks (cutoff six attacks per year), presence of clinical tophus (yes or no), uric acid level (>80 mg/L or 480 micromol/L) and age of onset (<30 years) .	8 months
Secondary	Relation between CKD and sex	Relation between CKD and sex (Male/ Female)	8 months
Secondary	Relation between gout and sex	Relation between gout and sex (Male/ Female)	8 months
Secondary	Relation between CKD and age	Relation between CKD and age	8 months
Secondary	Relation between gout and age	Relation between gout and age	8 months
Secondary	Relation between CKD and Body Mass Index (BMI)	Relation between CKD and Body Mass Index (BMI) in kg/m^2	8 months
Secondary	Link between gout and Body Mass Index (BMI)	Link between gout and Body Mass Index (BMI) in kg/m^2	8 months
Secondary	Relation between CKD and the Body Fat Percentage	Relation between CKD and the Body Fat Percentage in Percentage (%)	8 months
Secondary	Relation between gout and the Body Fat Percentage	Relation between gout and the Body Fat Percentage in Percentage (%)	8 months
Secondary	Relation between CKD and Muscle Mass Percentage	Relation between CKD and Muscle Mass Percentage in Percentage (%)	8 months
Secondary	Relation between gout and Muscle Mass Percentage	Relation between gout and Muscle Mass Percentage in Percentage (%)	8 months
Secondary	Relation between CKD and Basal Metabolism	Relation between CKD and Basal Metabolism in Joules	8 months
Secondary	Relation between gout and Basal Metabolism	Relation between gout and Basal Metabolism in Joules	8 months
Secondary	Relation between CKD and Visceral Fat Percentage	Relation between CKD and Visceral Fat Percentage in Percentage	8 months
Secondary	Relation between gout and Visceral Fat Percentage	Relation between gout and Visceral Fat Percentage in Percentage	8 months
Secondary	Relation between CKD and height	Relation between CKD and height in meters	8 months
Secondary	Relation between gout and height	Relation between gout and height in centimeters	8 months
Secondary	Relation between CKD and waist size	Relation between CKD and waist size in centimeters	8 months
Secondary	Relation between gout and waist size	Relationbetween gout and waist size in centimeters	8 months
Secondary	Relation between CKD and hip circumference	Relation between CKD and hip circumference in centimeters	8 months
Secondary	Relation between gout and hip circumference	Relation between gout and hip circumference in centimeters	8 months
Secondary	Relation between CKD and waist/hip ratio	Relation between CKD and waist/hip ratio	8 months
Secondary	Relation between gout and waist/hip ratio	Relation between gout and waist/hip ratio	8 months
Secondary	Mendelian randomization	Mendelian randomization uses measured variation in genes to interrogate the causal effect of an exposure on comorbidities development	8 months