MR Fat Quantification and Elastography During a Very Low-calorie-ketogenic Diet (Pronokal Method®) vs a Low Calorie Diet

Pilot Study Fatty Liver and Obesity: MR Fat Quantification and MR Elastography During a Very Low-calorie-ketogenic Diet (Pronokal Method®) Versus a Low Calorie Diet

Prospective, multicenter, open-label, randomized and controlled study of the effects of weight loss and reduced visceral fat on non-alcoholic fat infiltration into liver after a very low calorie ketogenic diet (VLCK diet) (Pronokal® Method) versus a hypocaloric diet, with a 6-month follow-up.

Study Overview

• Status: Completed
• Conditions: Liver Fat
• Intervention / Treatment: Other: PronoKal Method; Other: Low calorie diet

Detailed Description

The investigators will include obese patients with BMI higher than 30 kg / m2 to follow a standardized multidisciplinary weight-loss program (PronoKal® Method), which consists of a very-low-calorie diet, into which natural foods are gradually reintroduced, accompanied by physical exercise and emotional support, versus hypocaloric diet.

The aim of this study are see the reduction of fatty liver, visceral fat and improvement of hepatic stiffness during the weight loss treatment.

Patients will be visited monthly and data will recorded on 4 occasions: pre-inclusion, initial visit, 2-months visit (end of ketosis) and 6-months visit.

Hepatic fatty infiltration and visceral fat will be scanned by MRI and hepatic stiffness will be assessed by MR Elastography at: baseline, 2 months and 6 months. Also will be recorded anthropometric data (weight, BMI, waist circumference) and complete blood tests.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients of either sex, older than 18 years
• Obese patients with BMI equal or over 30kg/m2
• Patients who agree to participate and sign the Informed Consent

Exclusion Criteria:

• Pregnant or lactating women.
• Patients weighing over 140 kg (by limitation of the MRI device)
• Patients on anti-obesity drugs (eg, sibutramine, orlistat and liraglutide) or weight-interfering medications (eg, topiramate). In such cases a wash out period of 3 months is required.
• Patients with alcohol intake > 20 g/day in women and > 30 g/day in men.
• Patients with liver failure or with pathologies that may affect the liver
• Patients with other causes of liver steatosis: chronic viral hepatitis and/or drug intake (corticosteroids, estrogens, NSAIDs, calcium antagonists, amiodarone, tamoxifen, tetracyclines, chloroquine, antiretrovirals, perhexiline).
• Patients with eating disorders.
• Patients with any psychiatric disorder (eg schizophrenia, bipolar disorder, substance abuse, severe depression).
• Patients receiving dicumarinic anticoagulants (Sintrom®).
• Patients taking corticosteroids.
• Patients with severe kidney failure (gfr <30).
• Patients with type 1 and type 2 diabetes mellitus.
• Patients with hemopathies, including coagulation disorders
• Patients with cardiovascular or cerebrovascular disease (of heart rate disorders, recent infarction [<6m], unstable angina, decompensated heart failure, recent stroke [<6m]).
• Patients in acute attack of gout.
• Patients with renal lithiasis verified by ultrasound.
• Patients with cholelithiasis verified by ultrasound.
• Patients with electrolyte imbalance, according to medical criteria.
• Patients with orthostatic hypotension.
• Patients with cancer or history of cancer who have not been discharged from oncology
• Patients who are not expected to attend follow-up visits

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VLCK diet group; Subjects undergoing treatment with weight loss program PronoKal Method	Other: PronoKal Method; Multidisciplinary program of weight loss based on diet (initially ketogenic diet), physical activity and emotional support
Active Comparator: Control group; Subjects undergoing treatment with low calorie diet	Other: Low calorie diet; Balanced hypocaloric diet (caloric intake 10% below basal metabolic rate) accompanied by physical exercise.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver fatty infiltration at 6 months	Liver fatty infiltration percentage, measured by a MRI technique of fat liver quantification, fat at the end of treatment	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver fatty infiltration at 2 months	Liver fatty infiltration percentage, measured by a MRI technique of fat liver quantification, at the end of ketosis	2 months
Visceral fat at 2 months	Viceral fat measured by the area in squared centimeters at the level of the 3rd vertebrae, using MRI technique, at the end of ketosis.	2 months
Visceral fat at 6 months	Viceral fat measured by the area in squared centimeters at the level of the 3rd vertebrae, using MRI technique, at the end of treatment.	6 months
Liver stiffness at 2 months	Liver stiffness detected by MR Elastography at the end of ketosis	2 months
Liver stiffness at 6 months	Liver stiffness detected by MR Elastography at the end of treatment	6 months
Size of adrenal gland at 2 months	Linear size in centimetres of adrenal gland at the end of ketosis, measured by MRI.	2 months
Size of adrenal gland at 6 months	Linear size in centimetres of adrenal gland at the end of treatment, measured by MRI.	6 months
Body Weight loss at 2 months	Change in body weight from baseline to end of ketosis.	2 months
Body Weight loss at 6 months	Change in body weight from baseline to end of treatment.	6 months
Salivary cortisol levels at 2 months	Salivary cortisol levels at the end of ketosis	2 months
Salivary cortisol levels at 6 months	Salivary cortisol levels at the end of treatment	6 months

Collaborators and Investigators

• Sponsor: Protein Supplies SL
• Investigators: Principal Investigator: Walmir Coutinho, Ph, IEDE - Instituto Estadual de Diabetes e Endocrinologia; Principal Investigator: Guilherme Moura da Cunha, Ph, CDPI - Clínica de Diagnóstico por Imagen

Publications and helpful links

General Publications

• Cunha GM, Guzman G, Correa De Mello LL, Trein B, Spina L, Bussade I, Marques Prata J, Sajoux I, Countinho W. Efficacy of a 2-Month Very Low-Calorie Ketogenic Diet (VLCKD) Compared to a Standard Low-Calorie Diet in Reducing Visceral and Liver Fat Accumulation in Patients With Obesity. Front Endocrinol (Lausanne). 2020 Sep 14;11:607. doi: 10.3389/fendo.2020.00607. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (Actual): September 12, 2016
• Primary Completion (Actual): July 4, 2017
• Study Completion (Actual): October 25, 2017

Study Registration Dates

• First Submitted: March 13, 2020
• First Submitted That Met QC Criteria: March 23, 2020
• First Posted (Actual): March 26, 2020

Study Record Updates

• Last Update Posted (Actual): March 26, 2020
• Last Update Submitted That Met QC Criteria: March 23, 2020
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Low Calorie Diet; Fat reduction; Low-Calorie-Ketogenic diet; Pronokal Method®
• Other Study ID Numbers: PNK-FATLIV-2016-04

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No