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出境医 / 临床实验 / Effect of a Very Low-Calorie Ketogenic Diet on Gut Microbiota and Fat Distribution

Effect of a Very Low-Calorie Ketogenic Diet on Gut Microbiota and Fat Distribution

Study Description
Brief Summary:
Short-term interventions that use very low-calorie ketogenic diets and meal replacements may be prescribed for selected overweight or obese patients with type 2 diabetes or prediabetes. Few, inconsistent data are available on protein intake from various sources on body weight, the composition of gut microbiota and metabolic outcomes in these patients. The aim of the present study is to compare efficacy, safety and effect on microbiota composition of short-term isocaloric VLCKDs using whey proteins, vegetable proteins or animal proteins in obese patients with diabetes or prediabetes. 50 obese diabetic/prediabetic patients will be randomly assigned to three isocaloric VLCKD regimens (≤800 kcal/day) containing either whey, plant or animal proteins for 45 days. Outcome measures will be anthropometric parameters, vital signs, metabolic profile, body composition and microbiota assessment.

Condition or disease Intervention/treatment Phase
Obesity Dietary Supplement: Whey protein, vegetable protein or animal protein Not Applicable

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Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Very Low-calorie Ketogenic Diet (VLCKD) Influences Taxonomic Composition of the Gut Microbiota and Visceral Adipose Tissue Distribution in Obese Patients With Type 2 Diabetes or Prediabetes Depending on Protein Source
Estimated Study Start Date : July 2019
Estimated Primary Completion Date : October 2019
Estimated Study Completion Date : November 2019
Arms and Interventions
Arm Intervention/treatment
Experimental: Whey protein
VLCKD (780 kcal/day) low in carbohydrates (<50 g per day) and lipids (only 10 g of olive oil per day) for 45 days. High-biological-value protein preparations will be given four times per day, based on whey protein.
Dietary Supplement: Whey protein, vegetable protein or animal protein
meal replacements or animal protein

Active Comparator: Vegetable proteins
VLCKD (780 kcal/day) low in carbohydrates (<50 g per day) and lipids (only 10 g of olive oil per day) for 45 days. High-biological-value protein preparations will be given four times per day, based on vegetal protein derived from soya or green peas or cereals.
Dietary Supplement: Whey protein, vegetable protein or animal protein
meal replacements or animal protein

Active Comparator: Animal proteins
VLCKD (780 kcal/day) low in carbohydrates (<50 g per day) and lipids (only 10 g of olive oil per day) for 45 days.Patients will be given four meals per day containing natural animal protein (meat, fish, eggs, dairy products without whey protein).
Dietary Supplement: Whey protein, vegetable protein or animal protein
meal replacements or animal protein

Outcome Measures
Primary Outcome Measures :
  1. Body Mass Index change from baseline [ Time Frame: 45 days ]
    Body Mass Index will be calculated at baseline and after 45 days


Secondary Outcome Measures :
  1. Fat mass percentage (%) change from baseline [ Time Frame: 45 days ]
    Fat mass percentage will be assessed by DXA at baseline and after 45 days

  2. Visceral adipose tissue (gr) change from baseline [ Time Frame: 45 days ]
    Visceral adipose tissue will be assessed by DXA at baseline and after 45 days

  3. Microbiome taxonomic composition change from baseline [ Time Frame: 45 days ]
    Change in abundance of gut microbiome will be measured with stool sample collections at baseline and after 45 days

  4. Fasting glucose level (mg/dL) change from baseline [ Time Frame: 45 days ]
    blood glucose will be measured at baseline and after 45 days

  5. Fasting Insulin level (mcU/mL) change from baseline [ Time Frame: 45 days ]
    insulin will be measured at baseline and after 45 days

  6. Fasting Cholesterol level (mg/dL) change from baseline [ Time Frame: 45 days ]
    Fasting Cholesterol will be measured at baseline and after 45 days

  7. Muscle strength (kg) change from baseline [ Time Frame: 45 days ]
    Muscle strength will be assessed with a handgrip test at baseline and after 45 days

  8. Quality of life (subjective unit) change from baseline [ Time Frame: 45 days ]
    Quality of life will be assessed through questionnaire

  9. Safety (subjective unit) change from baseline [ Time Frame: 45 days ]
    safety will be assessed through questionnaire


Eligibility Criteria
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Ages Eligible for Study:   50 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • obesity (BMI 30-40)
  • newly-diagnosed and untreated type 2 diabetes (fasting plasma glucose ≥ 126 mg/dL or HbA1c ≥ 6.5 mmol/L) or impaired fasting glycemia (fasting plasma glucose from 110mg/dl to 125mg/dl).
  • stable body weight in the previous 3 months

Exclusion Criteria:

known hypersensitivity to one or more components used in the protocol products; history of renal, cardiac, cerebrovascular or gastrointestinal diseases; psychiatric disturbances; hydroelectrolytic alterations, diagnosis of type 1 diabetes lack of informed consent; history of or planned weight loss surgery

Contacts and Locations

Contacts
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Contact: Lucio Gnessi, MD PhD +390649970721 lucio.gnessi@uniroma1.it
Contact: Mikiko Watanabe, MD +393483244207 mikiko.watanabe@uniroma1.it

Locations
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Italy
Sapienza University of Rome Recruiting
Roma, RM, Italy, 00161
Contact: Lucio Gnessi, MD PhD    0649970721    lucio.gnessi@uniroma1.it   
Contact: Mikiko Watanabe, MD       mikiko.watanabe@uniroma1.it   
Sponsors and Collaborators
University of Roma La Sapienza
Investigators
Layout table for investigator information
Principal Investigator: Lucio Gnessi, MD PhD Sapienza University of Rome
Tracking Information
First Submitted Date  ICMJE July 5, 2019
First Posted Date  ICMJE July 15, 2019
Last Update Posted Date July 15, 2019
Estimated Study Start Date  ICMJE July 2019
Estimated Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 12, 2019)
Body Mass Index change from baseline [ Time Frame: 45 days ]
Body Mass Index will be calculated at baseline and after 45 days
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: July 12, 2019)
  • Fat mass percentage (%) change from baseline [ Time Frame: 45 days ]
    Fat mass percentage will be assessed by DXA at baseline and after 45 days
  • Visceral adipose tissue (gr) change from baseline [ Time Frame: 45 days ]
    Visceral adipose tissue will be assessed by DXA at baseline and after 45 days
  • Microbiome taxonomic composition change from baseline [ Time Frame: 45 days ]
    Change in abundance of gut microbiome will be measured with stool sample collections at baseline and after 45 days
  • Fasting glucose level (mg/dL) change from baseline [ Time Frame: 45 days ]
    blood glucose will be measured at baseline and after 45 days
  • Fasting Insulin level (mcU/mL) change from baseline [ Time Frame: 45 days ]
    insulin will be measured at baseline and after 45 days
  • Fasting Cholesterol level (mg/dL) change from baseline [ Time Frame: 45 days ]
    Fasting Cholesterol will be measured at baseline and after 45 days
  • Muscle strength (kg) change from baseline [ Time Frame: 45 days ]
    Muscle strength will be assessed with a handgrip test at baseline and after 45 days
  • Quality of life (subjective unit) change from baseline [ Time Frame: 45 days ]
    Quality of life will be assessed through questionnaire
  • Safety (subjective unit) change from baseline [ Time Frame: 45 days ]
    safety will be assessed through questionnaire
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of a Very Low-Calorie Ketogenic Diet on Gut Microbiota and Fat Distribution
Official Title  ICMJE Very Low-calorie Ketogenic Diet (VLCKD) Influences Taxonomic Composition of the Gut Microbiota and Visceral Adipose Tissue Distribution in Obese Patients With Type 2 Diabetes or Prediabetes Depending on Protein Source
Brief Summary Short-term interventions that use very low-calorie ketogenic diets and meal replacements may be prescribed for selected overweight or obese patients with type 2 diabetes or prediabetes. Few, inconsistent data are available on protein intake from various sources on body weight, the composition of gut microbiota and metabolic outcomes in these patients. The aim of the present study is to compare efficacy, safety and effect on microbiota composition of short-term isocaloric VLCKDs using whey proteins, vegetable proteins or animal proteins in obese patients with diabetes or prediabetes. 50 obese diabetic/prediabetic patients will be randomly assigned to three isocaloric VLCKD regimens (≤800 kcal/day) containing either whey, plant or animal proteins for 45 days. Outcome measures will be anthropometric parameters, vital signs, metabolic profile, body composition and microbiota assessment.
Detailed Description

Short-term interventions that use very low-calorie ketogenic diets and meal replacements may be prescribed for selected overweight or obese patients with type 2 diabetes or prediabetes. Few, inconsistent data are available on protein intake from various sources on body weight, the composition of gut microbiota and metabolic outcomes in these patients. The aim of the present study is to compare efficacy, safety and effect on microbiota composition of short-term isocaloric VLCKDs using whey proteins, vegetable proteins or animal proteins in obese patients with diabetes or prediabetes. 50 obese diabetic/prediabetic patients will be randomly assigned to three isocaloric VLCKD regimens (≤800 kcal/day) containing either whey, plant or animal proteins. Outcome measures will be anthropometric parameters, vital signs, metabolic profile, body composition and microbiota assessment. The patients will be assessed at baseline (T0) and every two weeks (T15, T30) up to day 45 (T45) when they will be finally evaluated. Patients will be given support and counselling to enhance their compliance. The patients will also be instructed to have moderate-intensity physical activity (e.g., 30 minutes walking every day) during the study.

Anthropometric parameters Body weight, blood pressure (systolic and diastolic), heart rate, waist and hip circumference will be measured at baseline (T0), every two weeks up to the end of the trial (T45).

Blood and urine chemistry Complete Blood Count (CBC), electrolytes (chloride, calcium, potassium, sodium, magnesium), fasting glucose, insulin, lipids (total and fractionated cholesterol and triglycerides) and proteins, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), plasma creatinine, blood urea nitrogen (BUN), alanine transferase (AST), aspartate transaminase (ALT), uric acid and estimated Glomerular Filtration Rate (using the Modification of Diet in Renal Disease study equation MDRD-eGFR) will be determined at baseline and after 45 days.

The overnight fasting plasma levels of Insulin Like Growth Factor-1 (IGF-1) will be measured using commercially available ELISA kits. Urine tests will be performed at baseline and every other week until the end of the study.

Dual-Energy-X-ray Absorptiometry measurement (DEXA) Body composition, total and regional body fat mass (FM) and fat-free mass (FFM), will be measured using DEXA (Hologic 4500 RDR) at baseline and at the end of the trial.

Visceral adipose tissue (VAT) will be calculated using a fully automated software. DEXA-VAT will be measured in a 5 cm wide area placed in the abdominal region just above the iliac crest, at a level that approximately coincides with the 5th lumbar vertebrae on the whole body DEXA scan. The VAT will be estimated by subtracting subcutaneous fat from the total abdominal fat by means of an algorithm.

Muscular strength Muscle strength will be measured through a digital dynamometer handgrip at T0 and T45. Before starting, patients will be asked to squeeze as hard as possible the dynamometer for at least 3 seconds. Three measurements will be repeated with both the dominant and non-dominant arms. The highest value measured will be recorded as the maximum grip force.

Taxonomic composition of the gut microbiome Fecal sampling will be done using sterile swab and tubes DNA purity will be evaluated based on A260/A280 ratio using a spectrophotometer. DNA integrity and size will be assessed by 1.5% agarose gel electrophoresis. The V3-V4 region of the 16S ribosomal RNA gene will be amplified. Polymerase Chain Reaction (PCR) amplicons will be purified and amplified following the Nextera XT Index protocol. The processed reads will be clustered and the operational taxonomic units will be assigned to taxa.

Data obtained will be expressed as mean values ±Standard Deviation (SD) and finally processed to ascertain whether statistical differences among them can be demonstrated, using appropriate methods. In particular, the analysis of variance (ANOVA) at different times will be used for efficacy and safety data, such as weight reduction, changes in anthropometric measures, FM and FFM and variation of the metabolic parameters. P values <0.05 will be considered statistically significant.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Obesity
Intervention  ICMJE Dietary Supplement: Whey protein, vegetable protein or animal protein
meal replacements or animal protein
Study Arms  ICMJE
  • Experimental: Whey protein
    VLCKD (780 kcal/day) low in carbohydrates (<50 g per day) and lipids (only 10 g of olive oil per day) for 45 days. High-biological-value protein preparations will be given four times per day, based on whey protein.
    Intervention: Dietary Supplement: Whey protein, vegetable protein or animal protein
  • Active Comparator: Vegetable proteins
    VLCKD (780 kcal/day) low in carbohydrates (<50 g per day) and lipids (only 10 g of olive oil per day) for 45 days. High-biological-value protein preparations will be given four times per day, based on vegetal protein derived from soya or green peas or cereals.
    Intervention: Dietary Supplement: Whey protein, vegetable protein or animal protein
  • Active Comparator: Animal proteins
    VLCKD (780 kcal/day) low in carbohydrates (<50 g per day) and lipids (only 10 g of olive oil per day) for 45 days.Patients will be given four meals per day containing natural animal protein (meat, fish, eggs, dairy products without whey protein).
    Intervention: Dietary Supplement: Whey protein, vegetable protein or animal protein
Publications * Basciani S, Camajani E, Contini S, Persichetti A, Risi R, Bertoldi L, Strigari L, Prossomariti G, Watanabe M, Mariani S, Lubrano C, Genco A, Spera G, Gnessi L. Very-Low-Calorie Ketogenic Diets With Whey, Vegetable, or Animal Protein in Patients With Obesity: A Randomized Pilot Study. J Clin Endocrinol Metab. 2020 Sep 1;105(9). pii: dgaa336. doi: 10.1210/clinem/dgaa336.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 12, 2019)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2019
Estimated Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • obesity (BMI 30-40)
  • newly-diagnosed and untreated type 2 diabetes (fasting plasma glucose ≥ 126 mg/dL or HbA1c ≥ 6.5 mmol/L) or impaired fasting glycemia (fasting plasma glucose from 110mg/dl to 125mg/dl).
  • stable body weight in the previous 3 months

Exclusion Criteria:

known hypersensitivity to one or more components used in the protocol products; history of renal, cardiac, cerebrovascular or gastrointestinal diseases; psychiatric disturbances; hydroelectrolytic alterations, diagnosis of type 1 diabetes lack of informed consent; history of or planned weight loss surgery

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Lucio Gnessi, MD PhD +390649970721 lucio.gnessi@uniroma1.it
Contact: Mikiko Watanabe, MD +393483244207 mikiko.watanabe@uniroma1.it
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04019431
Other Study ID Numbers  ICMJE U1111-1236-5158
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Lucio Gnessi, University of Roma La Sapienza
Study Sponsor  ICMJE University of Roma La Sapienza
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Lucio Gnessi, MD PhD Sapienza University of Rome
PRS Account University of Roma La Sapienza
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP