Dietary Intervention in Obesity-related Glomerulopathy (ORG-VLCD-2022)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Obesity; Glomerulopathy
• Intervention / Treatment: Other: Optisource® Plus: Very Low Calorie Diet treatment; Other: Hypocaloric Mediterranean Diet

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.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: José Carlos Fernández García, MD, PhD.; Phone Number: +34 951034016; Email: josecarlosfdezgarcia@hotmail.com
• Study Contact Backup: Name: Isabel María Cornejo Pareja, MD, PhD.; Phone Number: +34 951034016; Email: isabelmaria_cornejo@hotmail.com

Study Locations

• Spain
  • Málaga, Spain, 29009
    • Recruiting
    • Hospital Regional Universitario de Málaga.
    • Contact: José Carlos Fernández García, MD, PhD; Phone Number: +34 951034016

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Very Low Calorie Diet (VLCD); 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; 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)
ACTIVE_COMPARATOR: Hypocaloric Mediterranean diet; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud
• Investigators: Principal Investigator: José Carlos Fernández García, MD, PhD., Hospital Regional Universitario de Málaga - FIMABIS

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 18, 2022
• Primary Completion (ANTICIPATED): September 1, 2023
• Study Completion (ANTICIPATED): September 1, 2024

Study Registration Dates

• First Submitted: February 1, 2022
• First Submitted That Met QC Criteria: March 15, 2022
• First Posted (ACTUAL): March 24, 2022

Study Record Updates

• Last Update Posted (ACTUAL): July 25, 2022
• Last Update Submitted That Met QC Criteria: July 21, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Obesity; weight loss; diet; Albuminuria; kidney function; elastography
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity
• Other Study ID Numbers: ORG-VLCD-2022

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No