Dietary Intervention in Obesity-related Glomerulopathy

Study Overview
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Brief Summary
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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
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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.

Official Title
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Efficacy of a Very Low Calorie Diet or a Hypocaloric Mediterranean Diet on Albuminuria and Renal Function in Patients With Obesity-related Glomerulopathy: a Randomized Clinical Trial

Conditions
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Obesity, Glomerulopathy

Intervention / Treatment
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* Other: Optisource® Plus: Very Low Calorie Diet treatment
* Other: Hypocaloric Mediterranean Diet


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Very Low Calorie Diet (VLCD)<br>Patients randomized to this group will receive a VLCD, which consists of a replacement diet based on a liquid enteral formula (46% carbohydrates, 19% fat and 32% protein; 654 Kcal/day): OPTISOURCE® PLUS, taken as 3 shakes a day. In addition, participants may consume 2 pieces of fruit/day (about 250 g/day) and up to 300 g/day of non-starchy vegetables according to the list of foods that will be provided to patients; this will constitute a total daily energy intake of about 800 Kcal. In addition, protein intake (0.8 to 1.3 g/kg/day of adjusted weight) will be adjusted by adding Resource® Instant Protein individually, depending on the anthropometry and the renal function of the patients (to preserve fat free mass, whose loss has been correlated with subsequent weight recovery) | Other: Optisource® Plus: Very Low Calorie Diet treatment<br>* Patients randomized to this group will receive a VLCD, which consists of a replacement diet based on a liquid enteral formula (46% carbohydrates, 19% fat and 32% protein; 654 Kcal/day): OPTISOURCE® PLUS, taken as 3 shakes a day. In addition, participants may consume 2 pieces of fruit/day (about 250 g/day) and up to 300 g/day of non-starchy vegetables according to the list of foods that will be provided to patients; this will constitute a total daily energy intake of about 800 Kcal. In addition, protein intake (0.8 to 1.3 g/kg/day of adjusted weight) will be adjusted by adding Resource® Instant Protein individually, depending on the anthropometry and the renal function of the patients (to preserve fat free mass, whose loss has been correlated with subsequent weight recovery)<br>|
| Active Comparator: Hypocaloric Mediterranean diet<br>Randomized 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. | Other: Hypocaloric Mediterranean Diet<br>* Randomized 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in albuminuria | Albuminuria in mg/g | From baseline to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in glomerular filtration (kidney function) | Calculated with the formula CKD-EPI and measured in ml/min/1,73 m2 | From baseline to 6 months | 
| Cystatin C levels (kidney function) | Cystatin C in ng/ml | From baseline to 6 months | 
| BMI (body mass index) | kg/m2 | From baseline to 6 months | 
| Changes in total body water (TBW) | Measured in liters | From baseline to 6 months | 
| Changes in extracellular water (ECW) | Measured in liters | From baseline to 6 months | 
| Changes in intracellular water (ICW) | Measured in liters | From baseline to 6 months | 
| Changes in fat free mass (FFM) | Measured in kilograms | From baseline to 6 months | 
| Changes in fat free mass index (FFMI) | Measured in Kg/m2 | From baseline to 6 months | 
| Changes in fat mass (FM) | Measured in Kilograms | From baseline to 6 months | 
| Changes in fat mass index (FMI) | Measured in Kg/m2 | From baseline to 6 months | 
| Changes in body cell mass (BCM) | Measured in kilograms | From baseline to 6 months | 
| Changes in body cell mass index (BCMI) | Measured in Kg/m2 | From baseline to 6 months | 
| Changes in appendicular skeletal muscle mass (ASMM) | Measured in kilograms | From baseline to 6 months | 
| Changes in blood pressure | 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. | From baseline to 6 months | 
| Changes in inflammatory biomarkers (assess kidney failure) | Measured as Fetuin A, FGF-21 and TGF-β1 by ELISA (ng/ml) | From baseline to 6 months | 
| Changes in tubular and podocyte damage markers (assess kidney failure) | Measured as KIM-1 y NGAL by ELISA (ng/ml) | From baseline to 6 months | 
| Changes in adipokines | Measured as leptin, adiponectin and resistin by ELISA (ng/ml) | From baseline to 6 months | 
| Modifications in gut microbiota richness and diversity | 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 | From baseline to 6 months | 
| Modifications in gut microbiota abundance and composition | Differences between the study groups at different taxa levels (phyla, family, genus and species) will be evaluated with the QIIME2 software | From baseline to 6 months | 
| Modifications in gut microbiota functionality | 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 | From baseline to 6 months | 
| Modifications in shear-wave renal elastography | Changes in kilopascals (kPA) in renal sinus | From baseline to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Albuminuria, kidney function, diet, elastography, weight loss