Ignite Creation Date:
2024-10-26 @ 3:36 PM
Last Modification Date:
2024-10-26 @ 3:36 PM
Study NCT ID:
NCT06537466
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-07-25
Brief Title:
Ketogenic Diet in MASLD-related cACLD
Sponsor:
None
Organization:
None
Study Overview
Official Title:
A Randomised Controlled Tria of Low-calorie Ketogenic Diet Versus Mediterranean Diet in Patients With Compensated Advanced Chronic Liver Disease cACLD Secondary to Metabolic Dysfunction-Associated Steatotic Liver Disease MASLD
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The investigators hypothesize that very low ketogenic diet could represent a new therapeutic option in the management of patients with MASLD and cACLD Therefore the investigator propose a randomized controlled study that evaluates the impact of two dietary protocols -Mediterranean diet and very low ketogenic diet- the MD and the VLCKD in individuals with cACLD secondary to MASLD
Detailed Description:
The rationale of the study stems from evidence that patients with compensated advanced chronic liver disease cACLD secondary to MASLD have higher risk of liver-related morbidity liver decompensation hepatocellular carcinoma and mortality However todate the only approved drug by FDA in patients with MASH and F2-F3 fibrosis is Resmetirom but it is still not available in clinical practice outside US As a consequence currently and in the future the first-line treatment of MASLD involved weight loss and lifestyle modification such as physical exercise and dietary regimens based on calorie restriction In this context the Mediterranean diet is considered the standard but over the last decade the Very low-carbohydrate ketogenic diets VLCKD has gained immense popularity for its short-term positive effects on weight loss even if data on MASLD cACLD are lacking
Therefore considering recent evidence the investigator hypothesize that VLCKD could represent a new therapeutic option in the management of patients with MASLD and cACLD Specifically the investigator propose a randomized controlled study that evaluates the 48 week impact of two dietary protocols the MD and the VLCKD in individuals with cACLD secondary to MASLD with specific focus on weight loss 10 and on liver-related changes in liver stiffness by TE MRE and MRI-PDFF AST ALT and metabolic parameters see section on outcomes Here the investigators report the detailed proposed nutritional protocols
MEDITERRANEAN DIET This equilibrated diet has a caloric value 10 below the total metabolic expenditure of each individual The total metabolic expenditure is calculated from the basal metabolic expenditure based on the formula FAOWHOUN multiplied by the coefficient of activity which is calculated according to the physical activity of each participant The calories provide to this group range between 1400 and 1800 kcalday The ration of macronutrients provided is 45-55 arbohydrates15-25 proteins and 25-35 fat in addition to a recommended intake of 20-40 gday of fiber in the form of vegetables and fruits
VERY LOW-CARBOHYDRATE KETOGENIC DIETS The VLCKD ketogenic protocol entails a caloric intake 800 calories a protein intake calculated based on individual needs 12 02 gkgideal body weight low carbohydrate content approximately 45-55 g of carbohydrates per day and low lipids 10-15gday Vitamins and minerals Unlimited vegetables
The Kalibra protocol consists of 3 stages
WEIGHT LOSS Ketogenic metabolism is activated by reduced carbohydrate intake As an accessory phenomenon to lipolysis and the catabolism of fat reserves in adipose tissue there is a physiological production of ketone bodies acetoacetate beta-hydroxybutyrate acetone which represent a water-soluble and readily available energy source for many tissues in the body brain heart and muscles Continuous ketogenesis in addition to providing adequate energy intake is important to ensure the absence of hunger and a feeling of overall well-being throughout the weight loss period
TRANSITION gradual reintroduction of traditional foods In this phase the patient is reeducated to adopt a healthy and correct lifestyle in order to optimize and stabilize the results obtained in the attack phase
MAINTENANCE once the patient has achieved their overall goals they embark on a long-term nutritional path following the LARN Reference Intake Levels of Nutrients and Energy for the Italian population
In the first phase known as the classic ketogenic phase 21 days the protocol involves replacing all meals with Kalibra products accompanied by low-carbohydrate vegetables It is essential to include supplementation with trace elements minerals and vitamins The number of meals is determined based on the patients height in centimeters tab1
During the period when following the Kalibra method it is recommended to engage in physical activity for muscle toning of arms legs abdominals and glutes for 20-30 minutes at least 3 times a week A workout plan will be provided
Table 1 height in centimeters 160 160-170 170-180 180 Man 3-4 meals 4 meals 4-5 meals 5 meals Woman 5 meals 5 meals 6 meals 6-7 meals Tab1 Number of meal replacements based on height The second ketogenic phase called the Mitigated Diet 21 days involves reducing one Kalibra meal and the possibility of adding a portion of meat fish or eggs during one of the main meals accompanied by low-carbohydrate vegetables This allows for the maintenance of ketogenesis with consequent weight loss while also allowing the patient a reasonable level of social interaction
The Transition Phase represents an extremely important phase as it allows for the stabilization of the achieved weight through a gradual and measured increase in daily caloric intake
Each stage each lasting 21 days involves a caloric increase of approximately 150 kcal correlated with
Gradual numerical reduction of Kalibra protein foods
Increase in carbohydrate intake using low glycemic index foods
Introduction of foods from the Mediterranean diet
Progressive reduction of micronutritional supplementation The gradual caloric increase carried out in each of the 4 stages of the transition phase allows for the stabilization of the weight achieved with the Kalibra Method and its maintenance in the long term
Once the 4 stages of the transition are completed the patient will have finished their dietary journey and can then maintain the achieved results by daily application of a new lifestyle based on healthy and balanced nutrition taking into account fundamental aspects of the Mediterranean diet
Consume at least five servings of fruits and vegetables as they are rich in fiber vitamins minerals and antioxidant substances
Maintain proper hydration levels by consuming at least 15-2 liters of water per day
Start the day with a balanced breakfast to keep key hunger-regulating mechanisms in check resulting in reduced hunger throughout the day
Distribute daily caloric intake into at least four meals preferably adhering to the following percentages breakfast 27 lunch 36 snack 13 and dinner 24
Consume foods with a low glycemic index and load
Here the investigators report the detailed clinical and laboratory assessment
Nutritional status will be assessed using the Royal Free Hospital-Nutritional Prioritizing Tool RFH-NPT recommended by the European Society for Clinical Nutrition and Metabolism ESPEN guidelines for stratifying malnutrition risk in patients with liver diseases Evaluation will include Weight Kg height cm waist and hip circumference cm arm circumference cm triceps skinfold using a caliper thigh and suprapatellar root measurements Body mass index BMI will be calculated based on weight in kilograms and height in meters
Body composition will be assessed using bioimpedance analysis and muscle strength will be evaluated using a dynamometer A walking test will be conducted and the Liver Frailty Index will be calculated
Weight and circumferences will be assessed at each visit A comprehensive evaluation will be performed at the end of each phase
A 12-hour overnight fasting blood sample will be drawn at screening and during follow-up visits determine serum levels of Hb WBC ALT AST ɣ-glutamyltransferase ɣ-GT alkaline phosphatase total and direct bilirubin INR albumin total cholesterol HDL and LDL-cholesterol triglycerides plasma glucose concentration platelet count NAK and creatinine
Here the investigators report the detailed liver instrumental assessment
At baseline all patients will undergo an ultrasound US examination to evaluate liver structure and the presence of signs of portal hypertension Transient elastography will be performed using a FibroScan apparatus Echosens Paris France to measure liver stiffness and controlled attenuation parameter The median value of 10 successful acquisitions expressed in kilopascal kPa will be kept as representative of LSM The investigator will consider 10 successful acquisitions with a success rate of at least 60 and with an interquartile range lower than 20 as representative measurements During the same session MRE and MRI-PDFF will be used as diagnostic tools for noninvasive quantitative assessment of steatosis and liver fibrosis muscle mass will be also evaluated at L3 level Transient elastography will be repeated every three months US will be repeated every six months and the MRE and MRI-PDFF will be performed at the end of the therapy
Therefore considering recent evidence the investigator hypothesize that VLCKD could represent a new therapeutic option in the management of patients with MASLD and cACLD Specifically the investigator propose a randomized controlled study that evaluates the 48 week impact of two dietary protocols the MD and the VLCKD in individuals with cACLD secondary to MASLD with specific focus on weight loss 10 and on liver-related changes in liver stiffness by TE MRE and MRI-PDFF AST ALT and metabolic parameters see section on outcomes Here the investigators report the detailed proposed nutritional protocols
MEDITERRANEAN DIET This equilibrated diet has a caloric value 10 below the total metabolic expenditure of each individual The total metabolic expenditure is calculated from the basal metabolic expenditure based on the formula FAOWHOUN multiplied by the coefficient of activity which is calculated according to the physical activity of each participant The calories provide to this group range between 1400 and 1800 kcalday The ration of macronutrients provided is 45-55 arbohydrates15-25 proteins and 25-35 fat in addition to a recommended intake of 20-40 gday of fiber in the form of vegetables and fruits
VERY LOW-CARBOHYDRATE KETOGENIC DIETS The VLCKD ketogenic protocol entails a caloric intake 800 calories a protein intake calculated based on individual needs 12 02 gkgideal body weight low carbohydrate content approximately 45-55 g of carbohydrates per day and low lipids 10-15gday Vitamins and minerals Unlimited vegetables
The Kalibra protocol consists of 3 stages
WEIGHT LOSS Ketogenic metabolism is activated by reduced carbohydrate intake As an accessory phenomenon to lipolysis and the catabolism of fat reserves in adipose tissue there is a physiological production of ketone bodies acetoacetate beta-hydroxybutyrate acetone which represent a water-soluble and readily available energy source for many tissues in the body brain heart and muscles Continuous ketogenesis in addition to providing adequate energy intake is important to ensure the absence of hunger and a feeling of overall well-being throughout the weight loss period
TRANSITION gradual reintroduction of traditional foods In this phase the patient is reeducated to adopt a healthy and correct lifestyle in order to optimize and stabilize the results obtained in the attack phase
MAINTENANCE once the patient has achieved their overall goals they embark on a long-term nutritional path following the LARN Reference Intake Levels of Nutrients and Energy for the Italian population
In the first phase known as the classic ketogenic phase 21 days the protocol involves replacing all meals with Kalibra products accompanied by low-carbohydrate vegetables It is essential to include supplementation with trace elements minerals and vitamins The number of meals is determined based on the patients height in centimeters tab1
During the period when following the Kalibra method it is recommended to engage in physical activity for muscle toning of arms legs abdominals and glutes for 20-30 minutes at least 3 times a week A workout plan will be provided
Table 1 height in centimeters 160 160-170 170-180 180 Man 3-4 meals 4 meals 4-5 meals 5 meals Woman 5 meals 5 meals 6 meals 6-7 meals Tab1 Number of meal replacements based on height The second ketogenic phase called the Mitigated Diet 21 days involves reducing one Kalibra meal and the possibility of adding a portion of meat fish or eggs during one of the main meals accompanied by low-carbohydrate vegetables This allows for the maintenance of ketogenesis with consequent weight loss while also allowing the patient a reasonable level of social interaction
The Transition Phase represents an extremely important phase as it allows for the stabilization of the achieved weight through a gradual and measured increase in daily caloric intake
Each stage each lasting 21 days involves a caloric increase of approximately 150 kcal correlated with
Gradual numerical reduction of Kalibra protein foods
Increase in carbohydrate intake using low glycemic index foods
Introduction of foods from the Mediterranean diet
Progressive reduction of micronutritional supplementation The gradual caloric increase carried out in each of the 4 stages of the transition phase allows for the stabilization of the weight achieved with the Kalibra Method and its maintenance in the long term
Once the 4 stages of the transition are completed the patient will have finished their dietary journey and can then maintain the achieved results by daily application of a new lifestyle based on healthy and balanced nutrition taking into account fundamental aspects of the Mediterranean diet
Consume at least five servings of fruits and vegetables as they are rich in fiber vitamins minerals and antioxidant substances
Maintain proper hydration levels by consuming at least 15-2 liters of water per day
Start the day with a balanced breakfast to keep key hunger-regulating mechanisms in check resulting in reduced hunger throughout the day
Distribute daily caloric intake into at least four meals preferably adhering to the following percentages breakfast 27 lunch 36 snack 13 and dinner 24
Consume foods with a low glycemic index and load
Here the investigators report the detailed clinical and laboratory assessment
Nutritional status will be assessed using the Royal Free Hospital-Nutritional Prioritizing Tool RFH-NPT recommended by the European Society for Clinical Nutrition and Metabolism ESPEN guidelines for stratifying malnutrition risk in patients with liver diseases Evaluation will include Weight Kg height cm waist and hip circumference cm arm circumference cm triceps skinfold using a caliper thigh and suprapatellar root measurements Body mass index BMI will be calculated based on weight in kilograms and height in meters
Body composition will be assessed using bioimpedance analysis and muscle strength will be evaluated using a dynamometer A walking test will be conducted and the Liver Frailty Index will be calculated
Weight and circumferences will be assessed at each visit A comprehensive evaluation will be performed at the end of each phase
A 12-hour overnight fasting blood sample will be drawn at screening and during follow-up visits determine serum levels of Hb WBC ALT AST ɣ-glutamyltransferase ɣ-GT alkaline phosphatase total and direct bilirubin INR albumin total cholesterol HDL and LDL-cholesterol triglycerides plasma glucose concentration platelet count NAK and creatinine
Here the investigators report the detailed liver instrumental assessment
At baseline all patients will undergo an ultrasound US examination to evaluate liver structure and the presence of signs of portal hypertension Transient elastography will be performed using a FibroScan apparatus Echosens Paris France to measure liver stiffness and controlled attenuation parameter The median value of 10 successful acquisitions expressed in kilopascal kPa will be kept as representative of LSM The investigator will consider 10 successful acquisitions with a success rate of at least 60 and with an interquartile range lower than 20 as representative measurements During the same session MRE and MRI-PDFF will be used as diagnostic tools for noninvasive quantitative assessment of steatosis and liver fibrosis muscle mass will be also evaluated at L3 level Transient elastography will be repeated every three months US will be repeated every six months and the MRE and MRI-PDFF will be performed at the end of the therapy
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None