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Effects of VLCKD in Metabolic Syndrome (KETO-MI)

Primary Purpose

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

Status
Recruiting
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
VLCKD diet with replacing meals
Hypocaloric mediterranean Diet
Sponsored by
Azienda Ospedaliero Universitaria Maggiore della Carita
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 2

Eligibility Criteria

25 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • : Italy Pediatric Endocrine Service of AOU Maggiore della Carità of Novara; SCDU of Pediatrics, Department of Health Sciences, University of Eastern PiedmontRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

VLCKD

Hypocaloric Mediterranean Diet

Arm Description

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 %.

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 %.

Outcomes

Primary Outcome Measures

Change in weight
Variation of body weight assessed through body mass index change (BMI)(kg/m2)
Change in body circumferences
Variation of body circumferences (waist, hips)
Change in metabolic control
Variation of blood glucose
Change in metabolic control
Change of cardio-metabolic risk factors: lipid profile

Secondary Outcome Measures

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

Full Information

First Posted
February 21, 2022
Last Updated
September 27, 2023
Sponsor
Azienda Ospedaliero Universitaria Maggiore della Carita
Collaborators
Laboratoire THERASCIENCE
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1. Study Identification

Unique Protocol Identification Number
NCT05275608
Brief Title
Effects of VLCKD in Metabolic Syndrome
Acronym
KETO-MI
Official Title
Effects of Very Low Calorie Ketogenic Diet on Microbiota, Adipose Tissue and Immunitary Regulation: Pilot Study on Patients With Metabolic Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 7, 2022 (Actual)
Primary Completion Date
September 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Azienda Ospedaliero Universitaria Maggiore della Carita
Collaborators
Laboratoire THERASCIENCE

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2, Non-alcoholic Fatty Liver Disease, Obesity, Metabolic Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
VLCKD
Arm Type
Experimental
Arm Description
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 %.
Arm Title
Hypocaloric Mediterranean Diet
Arm Type
Active Comparator
Arm Description
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 %.
Intervention Type
Dietary Supplement
Intervention Name(s)
VLCKD diet with replacing meals
Intervention Description
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.
Intervention Type
Behavioral
Intervention Name(s)
Hypocaloric mediterranean Diet
Intervention Description
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).
Primary Outcome Measure Information:
Title
Change in weight
Description
Variation of body weight assessed through body mass index change (BMI)(kg/m2)
Time Frame
Change from Baseline BMI at 15 days, 30 days, 60 days, 90 days
Title
Change in body circumferences
Description
Variation of body circumferences (waist, hips)
Time Frame
Change from Baseline circumferences at 15 days, 30 days, 60 days, 90 days
Title
Change in metabolic control
Description
Variation of blood glucose
Time Frame
Change from Baseline blood glucose at 15 days, 30 days, 60 days, 90 days
Title
Change in metabolic control
Description
Change of cardio-metabolic risk factors: lipid profile
Time Frame
Change from Baseline lipid profile at 15 days, 30 days, 60 days, 90 days
Secondary Outcome Measure Information:
Title
Change in Metabolic control
Description
Change of cardio-metabolic risk factors: insulin resistance (HOMA-IR)
Time Frame
Change from Baseline HOMA-IR at 15 days, 30 days, 60 days, 90 days
Title
Change in kidney profile
Description
Variation of serum creatinin
Time Frame
Change from Baseline Serum Creatinin at 15 days, 30 days, 60 days, 90 days
Title
Change in liver profile
Description
Variation of liver profile (AST, ALT, GGT, bilirubin)
Time Frame
Change from Baseline liver profile at 15 days, 30 days, 60 days, 90 days
Title
Change in uric acid
Description
Variation of uric acid in blood
Time Frame
Change from Baseline uric acid at 15 days, 30 days, 60 days, 90 days
Title
Change in blood pressure
Description
Variation of blood pressure (diastolic and sistolic)
Time Frame
Change from Baseline blood pressure at 15 days, 30 days, 60 days, 90 days
Title
Change in body composition
Description
Change of body composition (fat mass %) (BIVA)
Time Frame
Change from Baseline fat mass% at 15 days, 30 days, 60 days, 90 days
Title
Change in body composition
Description
Change of body composition (fat mass %) (DXA)
Time Frame
Change from Baseline fat mass% at 90 days
Title
Change in muscolar functionality
Description
Changes observed from functional tests (handgrip strenght)
Time Frame
Change from Baseline scores at 30, 90 days
Title
Change in muscolar functionality
Description
Changes observed from functional tests (short physical portable battery score)
Time Frame
Change from Baseline scores at 30, 90 days
Title
Change in muscolar functionality
Description
Changes observed from functional tests (time up and go test)
Time Frame
Change from Baseline scores at 30, 90 days
Title
Change in hormones
Description
Variation of hormones in blood (ghrelin, leptin, adiponectin)
Time Frame
Change from Baseline blood hormones at 15, 30 days, 60 days, 90 days
Title
Change in hormones
Description
Variation of hormones in blood (irisin)
Time Frame
Change from Baseline blood hormones at 15, 30 days, 60 days, 90 days
Title
Change in hormones
Description
Variation of hormones in blood (zonulin)
Time Frame
Change from Baseline blood hormones at 15, 30 days, 60 days, 90 days
Title
Change in hormones
Description
Variation of hormones in blood (asprosin)
Time Frame
Change from Baseline blood hormones at 15, 30 days, 60 days, 90 days
Title
Change in hormones
Description
Variation of hormones in blood (TSH)
Time Frame
Change from Baseline blood hormones at 15, 30 days, 60 days, 90 days
Title
Change in hormones
Description
Variation of hormones in blood (FT4)
Time Frame
Change from Baseline blood hormones at 15, 30 days, 60 days, 90 days
Title
Change in hormones
Description
Variation of hormones in blood (PTH)
Time Frame
Change from Baseline blood hormones at 15, 30 days, 60 days, 90 days
Title
Change in hormones
Description
Variation of hormones in blood (25OH vitamin D)
Time Frame
Change from Baseline blood hormones at 15, 30 days, 60 days, 90 days
Title
Change in hormones
Description
Variation of hormones in blood (PYY)
Time Frame
Change from Baseline blood hormones at 15, 30 days, 60 days, 90 days
Title
Change in hormones
Description
Variation of hormones in blood (IGF-1)
Time Frame
Change from Baseline blood hormones at 15, 30 days, 60 days, 90 days
Title
Change in blood ketones
Description
Variation of ketones in blood
Time Frame
Change from Baseline blood ketones at 15, 30 days, 60 days, 90 days
Title
Change in basal metabolic rate
Description
Variation of basal metabolic rate through indirect calorimetry
Time Frame
Change from Baseline basal metabolic rate at 90 days
Title
Change in urine ketones
Description
Variation of urine excretion in terms of ketones
Time Frame
Change from Baseline urine ketones at 15, 30 days, 60 days, 90 days
Title
Change in urine nitrogen excretion
Description
Variation of urine excretion in terms of nitrogen
Time Frame
Change from Baseline urine nitrogen at 15, 30 days, 60 days, 90 days
Title
Change in omics profile
Description
Variation of metabolomic profile of stools through liquid and gas chromatography
Time Frame
Change from Baseline omic profile of stools at 15, 30 days, 60 days, 90 days
Title
Change in omics profile
Description
Variation of lipidomic profile of stools through liquid and gas chromatography
Time Frame
Change from Baseline omic profile of stools at 15, 30 days, 60 days, 90 days
Title
Change in omics profile
Description
Variation of proteomic profile of stools through liquid and gas chromatography
Time Frame
Change from Baseline omic profile of stools at 15, 30 days, 60 days, 90 days
Title
Change in microbiota
Description
Variation of prevalence of microbiota phyla through DNA sequencing of stools
Time Frame
Change from Baseline of prevalence of microbiota phyla at 15, 30 days, 60 days, 90 days
Title
Change in inflammatory status
Description
Variation of inflammatory status in blood (C-reactive protein CRP)
Time Frame
Change from Baseline CRP and cytokines at 15, 30 days, 60 days, 90 days
Title
Change in inflammatory status
Description
Variation of inflammatory status in blood (cytokines count)
Time Frame
Change from Baseline cytokines at 15, 30 days, 60 days, 90 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Flavia Prdoam, Prof. MD
Phone
+39 0321 660 693
Email
flavia.prodam@med.uniupo.it
Facility Information:
Facility Name
: Italy Pediatric Endocrine Service of AOU Maggiore della Carità of Novara; SCDU of Pediatrics, Department of Health Sciences, University of Eastern Piedmont
City
Novara
ZIP/Postal Code
28100
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Flavia Prodam, Prof. MD
Phone
+39 0321 660 693
Email
flavia.prodam@med.uniupo.it

12. IPD Sharing Statement

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Effects of VLCKD in Metabolic Syndrome

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