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Dietary Intervention in Obesity-related Glomerulopathy

Not Applicable
Recruiting
Conditions
Obesity
Glomerulopathy
Interventions
Other: Hypocaloric Mediterranean Diet
Registration Number
NCT05294770
Lead Sponsor
Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud
Brief Summary

Obesity-related glomerulopathy (ORG) is a silent comorbidity associated with obesity whose incidence is increasing in parallel to the obesity epidemic. ORG is associated with serious health consequences including chronic kidney disease, end-stage renal disease, and increased mortality. Unfortunately, ORG has an absence of targeted therapy (except for the use of drugs blocking the renin-angiotensin system), and therefore the prognosis of this disease may be seriously compromised. Some previous studies have shown that weight loss could be effective to decrease albuminuria and reduce the declining in kidney function in subject with obesity. In line with this, in this study the investigators will evaluate the efficacy of two different dietary strategies for ORG, given the current lack of therapies for this condition. Thus, the investigators will conduct an open-label randomized controlled trial comparing a hypocaloric Mediterranean diet with a very-low calorie diet (VLCD), evaluating the efficacy on albuminuria reduction and changes in renal function. Also, the investigators will assess changes on body composition, blood pressure, markers of renal damage and inflammation, gut microbiota, and on renal ultrasound elastography.

Detailed Description

Our hypothesis is that a dietary strategy based on a very low calorie diet (VLCD) will produce a greater reduction in albuminuria than a hypocaloric Mediterranean diet in subjects with ORG. This improvement will be achieved through weight loss and changes in body composition, the reduction of blood pressure, the decrease in inflammatory, tubular and podocyte damage markers, modifications in adipokine concentrations, changes in the intestinal microbiota and in renal elastography.

The main objective of this clinical trial is to evaluate which dietary strategy (VLCD diet or Mediterranean hypocaloric diet) is more effective in reducing albuminuria and preserving renal function in patients with ORG.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
60
Inclusion Criteria
  • BMI ≥ 30 kg/m2
  • Albuminuria ≥ 150 mg/g
  • eGFR ≥ 30 ml/min/1,73 m²
  • Informed consent signed
  • All patients should receive a stable dose of ACE inhibitors or ARBs for at least 4 weeks prior to randomization. Before randomization; A stable dose will be considered to be the maximum dose indicated in the drug's SmPC or a dose that is not associated with unacceptable side effects in the patient.
Exclusion Criteria
  • Previous diagnosis of diabetes mellitus (defined by HbA1c ≥ 6.5% or baseline blood glucose ≥126 mg / dl or blood glucose 2 hours after oral glucose overload ≥200 mg / dl).
  • Treatment with oral hypoglycemic agents, insulin or GLP-1 receptor agonists.
  • Active cancer
  • History of liver tumor or acute or chronic liver diseases with impaired liver function: total bilirubin levels> 2.0 mg / dL or AST levels three times higher than the upper limit of normal.
  • Established cardiovascular disease (stroke, acute myocardial infarction, cardiac revascularization).
  • Uncontrolled hypertension (systolic blood pressure> 180 mmHg or diastolic blood pressure> 110 mmHg) despite adequate antihypertensive treatment.
  • Infection with HIV, HBV, HCV or other infection that can lead to secondary glomerular disease
  • Suspicion of primary glomerulopathy (except GAO).
  • Evidence of drug or alcohol abuse.
  • Serious underlying conditions that, in the opinion of the investigators, could affect the patient's ability to participate in the study.
  • Limited life expectancy (<12 months).
  • Pregnancy or breastfeeding.
  • Impossibility of following the indicated diet.
  • Inability to follow scheduled visits.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Hypocaloric Mediterranean dietHypocaloric Mediterranean DietRandomized participants in this group will be recommended to follow a Mediterranean Diet, based on the use of olive oil as the main source of visible fat and regular consumption of vegetables (≥2 servings/day), fruits (≥3 servings/day), legumes (≥3 servings/week) and fish (≥3 times a week), reducing the consumption of red meat or sausages (\<2 times a week) and eliminating the consumption of sugary drinks, pastries or industrial pastries. In this Mediterranean Diet, an energy restriction of 30% of the estimated energy needs (Harris-Benedict equation) will be established.
Primary Outcome Measures
NameTimeMethod
Changes in albuminuriaFrom baseline to 6 months

Albuminuria in mg/g

Secondary Outcome Measures
NameTimeMethod
Cystatin C levels (kidney function)From baseline to 6 months

Cystatin C in ng/ml

Changes in intracellular water (ICW)From baseline to 6 months

Measured in liters

Changes in fat free mass index (FFMI)From baseline to 6 months

Measured in Kg/m2

Changes in body cell mass index (BCMI)From baseline to 6 months

Measured in Kg/m2

Changes in total body water (TBW)From baseline to 6 months

Measured in liters

Changes in extracellular water (ECW)From baseline to 6 months

Measured in liters

Changes in fat mass (FM)From baseline to 6 months

Measured in Kilograms

Changes in fat mass index (FMI)From baseline to 6 months

Measured in Kg/m2

Modifications in shear-wave renal elastographyFrom baseline to 6 months

Changes in kilopascals (kPA) in renal sinus

Modifications in gut microbiota functionalityFrom baseline to 6 months

We will evaluate the differences between sudy groups in microbial functions, analyzed with the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt2) software, within the QIIME2 environment

Changes in glomerular filtration (kidney function)From baseline to 6 months

Calculated with the formula CKD-EPI and measured in ml/min/1,73 m2

BMI (body mass index)From baseline to 6 months

kg/m2

Changes in fat free mass (FFM)From baseline to 6 months

Measured in kilograms

Changes in appendicular skeletal muscle mass (ASMM)From baseline to 6 months

Measured in kilograms

Changes in adipokinesFrom baseline to 6 months

Measured as leptin, adiponectin and resistin by ELISA (ng/ml)

Changes in inflammatory biomarkers (assess kidney failure)From baseline to 6 months

Measured as Fetuin A, FGF-21 and TGF-β1 by ELISA (ng/ml)

Changes in body cell mass (BCM)From baseline to 6 months

Measured in kilograms

Changes in blood pressureFrom baseline to 6 months

We will perform a 24-hour Ambulatory Blood Pressure Measurement (ABPM) with the SpaceLab © OnTrak meter (Spacelabs Healthcare, Washington, USA), the newest ABPM meter from this recognized manufacturer. This ABPM meter is a clinically validated device with high precision and reliability.

Modifications in gut microbiota abundance and compositionFrom baseline to 6 months

Differences between the study groups at different taxa levels (phyla, family, genus and species) will be evaluated with the QIIME2 software

Changes in tubular and podocyte damage markers (assess kidney failure)From baseline to 6 months

Measured as KIM-1 y NGAL by ELISA (ng/ml)

Modifications in gut microbiota richness and diversityFrom baseline to 6 months

Differences in α- and β-diversities between study groups will be analyzed with the open-source Quantitative Insights into Microbial Ecology (QIIME2) software, through the diversity plugin

Trial Locations

Locations (1)

Hospital Regional Universitario de Málaga.

🇪🇸

Málaga, Spain

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