Effects of VLCKD in Metabolic Syndrome

Study Overview
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Brief Summary
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VLCKD has showed to be an impactful diet on several metabolism aspects and has proven to be useful for preventing and treating diabetes mellitus type 2, overweight, chronic inflammation and fatty liver. For this reason, the aim of this pilot study is to examinate the potential effect of a VLCKD on a group of patients that contemporarily have DM2, obesity and Non alcholic fatty liver disease (NAFLD), comparing the results with an ipocaloric diet based on Mediterranean Principles and Italian LARN (SINU 2014). This study will consider several interrelated outcomes such as anthropometric data, hematochemical and hormonal parameters, questionnaires, stool microbiota and omics, blood microvescicles, urine tests, instrumental tests (DXA, BIVA, ecographies), biopses and functional tests. 40 subjects will be evaluated and divided in two groups of 20 (VLCKD) and 20 (MedDiet).

Official Title
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Effects of Very Low Calorie Ketogenic Diet on Microbiota, Adipose Tissue and Immunitary Regulation: Pilot Study on Patients With Metabolic Syndrome

Conditions
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Diabetes Mellitus, Type 2, Non-alcoholic Fatty Liver Disease, Obesity, Metabolic Syndrome

Intervention / Treatment
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* Dietary Supplement: VLCKD diet with replacing meals
* Behavioral: Hypocaloric mediterranean Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 25-65 BMI 30-40 mg/m2 NAFLD DM2 drug-treated (metformin, SGLT2 inhibitors, GLP-1 analogues, DPPIV inhibitors, basal insulin) and HbA1c > 7 and < 10 %. Exclusion Criteria: Secondary obesity due to genetic or endocrinologic causes. renal disease with eGFR < 45 mL/min/1.73m2 or macroalbuminuria or calculosis insulin basal + bolus or HbA1c% >10.0% Other types of DM ipopituitarism or adrenal insufficiency antibiotics use less than 3 months before the first visit

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 65 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: VLCKD<br>20 Patients recruited from our endocrinology department that will keep the same medical visits frequency and drugs and accept to be randomized to one of the two groups. Inclusion criteria: Age 25-65 BMI 30-40 mg/m2 NAFLD DM2 drug-treated (metformin, SGLT2 inhibitors, GLP-1 analogues, DPPIV inhibitors, insulin) and HbA1c > 7 and < 10 %. | Dietary Supplement: VLCKD diet with replacing meals<br>* Patients will receive an accurate teaching + brochure on VLCKD diet from an expert dietician and freely receive the correct amount of supplements provided from Labotaoire Therascience (4 or 5 meals). The supplements contain (in total) between 600 and 800 kcal, mainly fats, 1,2/1,5 g/body weight of proteins, very low amount of charbohydrates (<30/40g/die), 10-20g fibers, + minerals and vitamins covering the needings of patients. After 6-8 weeks, 1 meal will be replaced with a natural dish rich in proteins.<br>|
| Active Comparator: Hypocaloric Mediterranean Diet<br>20 Patients recruited from our endocrinology department that will keep the same medical visits frequency and drugs and accept to be randomized to one of the two groups. Inclusion criteria: Age 25-65 BMI 30-40 mg/m2 NAFLD DM2 drug-treated (metformin, SGLT2 inhibitors, GLP-1 analogues, DPPIV inhibitors, insulin) and HbA1c > 7 and < 10 %. | Behavioral: Hypocaloric mediterranean Diet<br>* Patients will receive an accurate teaching + brochure on an hypocaloric Mediterranean style diet (LARN 2014) from an expert dietician. Patients will follow the istructions on grams and foods to eat. The calories will be around minus 400-500 kcal from energy requirement (measured by indirect calorimetry * physical activity score).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in weight | Variation of body weight assessed through body mass index change (BMI)(kg/m2) | Change from Baseline BMI at 15 days, 30 days, 60 days, 90 days | 
| Change in body circumferences | Variation of body circumferences (waist, hips) | Change from Baseline circumferences at 15 days, 30 days, 60 days, 90 days | 
| Change in metabolic control | Variation of blood glucose | Change from Baseline blood glucose at 15 days, 30 days, 60 days, 90 days | 
| Change in metabolic control | Change of cardio-metabolic risk factors: lipid profile | Change from Baseline lipid profile at 15 days, 30 days, 60 days, 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Metabolic control | Change of cardio-metabolic risk factors: insulin resistance (HOMA-IR) | Change from Baseline HOMA-IR at 15 days, 30 days, 60 days, 90 days | 
| Change in kidney profile | Variation of serum creatinin | Change from Baseline Serum Creatinin at 15 days, 30 days, 60 days, 90 days | 
| Change in liver profile | Variation of liver profile (AST, ALT, GGT, bilirubin) | Change from Baseline liver profile at 15 days, 30 days, 60 days, 90 days | 
| Change in uric acid | Variation of uric acid in blood | Change from Baseline uric acid at 15 days, 30 days, 60 days, 90 days | 
| Change in blood pressure | Variation of blood pressure (diastolic and sistolic) | Change from Baseline blood pressure at 15 days, 30 days, 60 days, 90 days | 
| Change in body composition | Change of body composition (fat mass %) (BIVA) | Change from Baseline fat mass% at 15 days, 30 days, 60 days, 90 days | 
| Change in body composition | Change of body composition (fat mass %) (DXA) | Change from Baseline fat mass% at 90 days | 
| Change in muscolar functionality | Changes observed from functional tests (handgrip strenght) | Change from Baseline scores at 30, 90 days | 
| Change in muscolar functionality | Changes observed from functional tests (short physical portable battery score) | Change from Baseline scores at 30, 90 days | 
| Change in muscolar functionality | Changes observed from functional tests (time up and go test) | Change from Baseline scores at 30, 90 days | 
| Change in hormones | Variation of hormones in blood (ghrelin, leptin, adiponectin) | Change from Baseline blood hormones at 15, 30 days, 60 days, 90 days | 
| Change in hormones | Variation of hormones in blood (irisin) | Change from Baseline blood hormones at 15, 30 days, 60 days, 90 days | 
| Change in hormones | Variation of hormones in blood (zonulin) | Change from Baseline blood hormones at 15, 30 days, 60 days, 90 days | 
| Change in hormones | Variation of hormones in blood (asprosin) | Change from Baseline blood hormones at 15, 30 days, 60 days, 90 days | 
| Change in hormones | Variation of hormones in blood (TSH) | Change from Baseline blood hormones at 15, 30 days, 60 days, 90 days | 
| Change in hormones | Variation of hormones in blood (FT4) | Change from Baseline blood hormones at 15, 30 days, 60 days, 90 days | 
| Change in hormones | Variation of hormones in blood (PTH) | Change from Baseline blood hormones at 15, 30 days, 60 days, 90 days | 
| Change in hormones | Variation of hormones in blood (25OH vitamin D) | Change from Baseline blood hormones at 15, 30 days, 60 days, 90 days | 
| Change in hormones | Variation of hormones in blood (PYY) | Change from Baseline blood hormones at 15, 30 days, 60 days, 90 days | 
| Change in hormones | Variation of hormones in blood (IGF-1) | Change from Baseline blood hormones at 15, 30 days, 60 days, 90 days | 
| Change in blood ketones | Variation of ketones in blood | Change from Baseline blood ketones at 15, 30 days, 60 days, 90 days | 
| Change in basal metabolic rate | Variation of basal metabolic rate through indirect calorimetry | Change from Baseline basal metabolic rate at 90 days | 
| Change in urine ketones | Variation of urine excretion in terms of ketones | Change from Baseline urine ketones at 15, 30 days, 60 days, 90 days | 
| Change in urine nitrogen excretion | Variation of urine excretion in terms of nitrogen | Change from Baseline urine nitrogen at 15, 30 days, 60 days, 90 days | 
| Change in omics profile | Variation of metabolomic profile of stools through liquid and gas chromatography | Change from Baseline omic profile of stools at 15, 30 days, 60 days, 90 days | 
| Change in omics profile | Variation of lipidomic profile of stools through liquid and gas chromatography | Change from Baseline omic profile of stools at 15, 30 days, 60 days, 90 days | 
| Change in omics profile | Variation of proteomic profile of stools through liquid and gas chromatography | Change from Baseline omic profile of stools at 15, 30 days, 60 days, 90 days | 
| Change in microbiota | Variation of prevalence of microbiota phyla through DNA sequencing of stools | Change from Baseline of prevalence of microbiota phyla at 15, 30 days, 60 days, 90 days | 
| Change in inflammatory status | Variation of inflammatory status in blood (C-reactive protein CRP) | Change from Baseline CRP and cytokines at 15, 30 days, 60 days, 90 days | 
| Change in inflammatory status | Variation of inflammatory status in blood (cytokines count) | Change from Baseline cytokines at 15, 30 days, 60 days, 90 days |