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

May 16, 2022 updated by: Lucio Gnessi, University of Roma La Sapienza

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

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.

Study Overview

Status

Completed

Conditions

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

Interventional

Enrollment (Actual)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • RM
      • Roma, RM, Italy, 00161
        • Sapienza University of Rome

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / 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.
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.
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).
meal replacements or animal protein

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Body Mass Index change from baseline
Time Frame: 45 days
Body Mass Index will be calculated at baseline and after 45 days
45 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Fat mass percentage (%) change from baseline
Time Frame: 45 days
Fat mass percentage will be assessed by DXA at baseline and after 45 days
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
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
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
45 days
Fasting Insulin level (mcU/mL) change from baseline
Time Frame: 45 days
insulin will be measured at baseline and after 45 days
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
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
45 days
Quality of life (subjective unit) change from baseline
Time Frame: 45 days
Quality of life will be assessed through questionnaire
45 days
Safety (subjective unit) change from baseline
Time Frame: 45 days
safety will be assessed through questionnaire
45 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Lucio Gnessi, MD PhD, University of Roma La Sapienza

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2019

Primary Completion (Actual)

October 1, 2019

Study Completion (Actual)

November 1, 2019

Study Registration Dates

First Submitted

July 5, 2019

First Submitted That Met QC Criteria

July 12, 2019

First Posted (Actual)

July 15, 2019

Study Record Updates

Last Update Posted (Actual)

May 17, 2022

Last Update Submitted That Met QC Criteria

May 16, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Other Study ID Numbers

  • U1111-1236-5158

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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