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

Obesity Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04019431
• Other study ID #: U1111-1236-5158
• Status: Completed
• Phase: N/A
• Start date: July 1, 2019
• Est. completion date: November 1, 2019

Study information

• Verified date: May 2022
• Source: University of Roma La Sapienza
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: November 1, 2019
• Est. primary completion date: October 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Obesity

Intervention

Dietary Supplement:
• Whey protein, vegetable protein or animal protein
meal replacements or animal protein

Locations

Country	Name	City	State
Italy	Sapienza University of Rome	Roma	RM

Sponsors (1)

Lead Sponsor	Collaborator
University of Roma La Sapienza

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Body Mass Index change from baseline	Body Mass Index will be calculated at baseline and after 45 days	45 days
Secondary	Fat mass percentage (%) change from baseline	Fat mass percentage will be assessed by DXA at baseline and after 45 days	45 days
Secondary	Visceral adipose tissue (gr) change from baseline	Visceral adipose tissue will be assessed by DXA at baseline and after 45 days	45 days
Secondary	Microbiome taxonomic composition change from baseline	Change in abundance of gut microbiome will be measured with stool sample collections at baseline and after 45 days	45 days
Secondary	Fasting glucose level (mg/dL) change from baseline	blood glucose will be measured at baseline and after 45 days	45 days
Secondary	Fasting Insulin level (mcU/mL) change from baseline	insulin will be measured at baseline and after 45 days	45 days
Secondary	Fasting Cholesterol level (mg/dL) change from baseline	Fasting Cholesterol will be measured at baseline and after 45 days	45 days
Secondary	Muscle strength (kg) change from baseline	Muscle strength will be assessed with a handgrip test at baseline and after 45 days	45 days
Secondary	Quality of life (subjective unit) change from baseline	Quality of life will be assessed through questionnaire	45 days
Secondary	Safety (subjective unit) change from baseline	safety will be assessed through questionnaire	45 days