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

NCT ID: NCT04019431

Last Updated: 2022-05-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-01
• Study Completion Date: 2019-11-01

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.

Conditions

Obesity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Whey protein, vegetable protein or animal protein

Intervention Type: DIETARY_SUPPLEMENT

meal replacements or animal protein

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.

Group Type: ACTIVE_COMPARATOR

Whey protein, vegetable protein or animal protein

Intervention Type: DIETARY_SUPPLEMENT

meal replacements or animal protein

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).

Group Type: ACTIVE_COMPARATOR

Whey protein, vegetable protein or animal protein

Intervention Type: DIETARY_SUPPLEMENT

meal replacements or animal protein

Interventions

Whey protein, vegetable protein or animal protein

meal replacements or animal protein

Intervention Type: DIETARY_SUPPLEMENT

Eligibility 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

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Roma La Sapienza

OTHER

Sponsor Role: lead

Responsible Party

Lucio Gnessi

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lucio Gnessi, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University of Roma La Sapienza

Locations

Sapienza University of Rome

Roma, RM, Italy

Countries

Italy

References

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):dgaa336. doi: 10.1210/clinem/dgaa336.

Reference Type: DERIVED

PMID: 32484877 (View on PubMed)

Other Identifiers

U1111-1236-5158

Identifier Type: -

Identifier Source: org_study_id