Role of the Very Low Calorie Ketogenic Diet (VLCKD) in Patients With Non-Alcoholic Steatohepatitis (NASH) With Fibrosis

NCT06308757 | Recruiting

• 1 other identifier: 495/2021/Sper/AOUBo
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the KETONASH study is to evaluate, in patients with metabolic-associated fatty liver disease (MAFLD) with non-alcoholic steatohepatitis (NASH) and significant liver fibrosis, the effect of a very low-calorie ketogenic diet (VLCKD) compared to that of a standard low-calorie diet (standard Mediterranean LCD - in accordance with the European Association for the Study of the Liver/European Society for Clinical Nutrition and Metabolism guidelines on MAFLD/NAFLD).

Conditions

NASH; NAFLD; Obesity; Liver Fibrosis

Keywords

vlckd; diet; ketogenic diet

Outcome Measures

Primary Outcomes (2)

• Change of at least one grade of liver fibrosis

  Histological change of liver fibrosis without worsening of NASH

  12 months

• Change of histological features of NASH

  NASH parameters variation. Improvement in disease activity is defined as decrease in NAFLD Activity Score (NAS) ≥1 points. The worsening of fibrosis is defined as any numerical increase in the stage.

  12 months

Secondary Outcomes (29)

• Histological NIH NASH CRN Score

  12 months

• Histological FLIP/SAF changes

  12 months

• Biochemical test changes 1

  12 months

• Biochemical test changes 2

  12 months

• Biochemical test changes 3

  12 months

Study Arms (2)

VLCKD arm

EXPERIMENTAL

The VLCKD dietary intervention consists of five phases: Ketogenic Low-Calorie Period (2 months): * Phase 1 (30 days - Visits 1-3): Ketogenic diet with low-fat content, 600 kcal/day. * Phase 2 (15 days - Visit 5): 660 kcal/day. * Phase 3 (15 days - Visit 5): 730 kcal/day Low-Calorie Period (2 months): Phase 4 (30 days - Visits 6-7): Hypocaloric diet with the reintroduction of different foods, 1,050 kcal/day. \- Phase 5 (30 days - Visits 7-8): 1,400 kcal/day. During these phases, the patient will receive nutritional supplementation with vitamins, trace elements, and omega-3 fatty acids. Throughout the very low-calorie ketogenic period, the patient will have three interim dietetic consultations (Visits 2-4) and a medical visit (Visit 5). During the low-calorie period, the patient will receive alternating two dietetic consultations (Visits 6 and 7) and one medical visit every 30 days (Visit 8).

Dietary Supplement: Very-low-calorie ketogenic diet (VLCKD) with meal replacements

Control LCD arm

ACTIVE COMPARATOR

The control LCD arm consists of a diet with natural low-calorie foods (1200-1500 kcal/day or a reduction of 500-1000 kcal/day compared to baseline) and a low glycemic index based on the "Mediterranean Diet" model, following the most recent guidelines on MAFLD/NAFLD. Similar to the VLCKD arm, for the entire duration of the dietetic treatment, the patient will alternately receive dietetic consultations and medical visits. At the end of the dietary intervention, patients from both study arms will continue with a controlled, low glycemic index diet tailored to the patient's basal metabolic rate (BMR) (estimated with bioimpedance assessment) for an additional six months. Both study arms will follow a physical activity schedule and will have psychological-motivational support.

Dietary Supplement: Mediterranean low-calorie diet (LCD)

Interventions

Very-low-calorie ketogenic diet (VLCKD) with meal replacements DIETARY_SUPPLEMENT

The VLCKD study arm will receive an experimental diet therapy with very-low-calorie ketogenic meal replacements (VLCKD) consisting of 5 successive phases (600 - 1500 kcal/day).

VLCKD arm

Mediterranean low-calorie diet (LCD) DIETARY_SUPPLEMENT

The Control arm LCD will receive standard Mediterranean type low-calorie diet (LCD) therapy by the most recent guidelines on MAFLD/NAFLD (1200-1500 kcal/day).

Control LCD arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged ≥18 years with histological diagnosis of NASH with evidence of fibrosis (defined according to NASH CRN) obtained no more than 6 months before enrollment;
• Stable weight for more than 6 months with BMI between 30-40 kg/m2;
• Patients in whom it is safe and feasible to proceed with liver biopsy and who consent to undergo liver biopsy after 12 months of enrollment to assess the effect of dietary treatment;
• Obtained informed consent.

You may not qualify if:

• BMI \<30 or BMI \>40
• Presence of evolved chronic liver disease into cirrhosis (histological F4 or elastometric LSM \>14 kPa)
• Type 1 diabetes mellitus
• Model for End-stage Liver Disease (MELD) score \>12, AST or ALT ≥5× ULN, HbA1c \>9.5%, INR ≥1.4, creatinine \>1.5 mg/dl, platelets \<100,000/mm3, and total bilirubin \>1.5 mg/dl.
• Concurrent presence of any other known chronic liver disease beyond MAFLD/NAFLD, such as alcoholic liver disease, viral (HCV/HBV), cholestatic-autoimmune (PBC/PSC/AIH), Wilson's disease, hemochromatosis, drug-induced liver injury (DILI), or the presence or suspicion of hepatocellular carcinoma (HCC);
• Average alcohol consumption exceeding 4/2 units/day (males/females) in the preceding 6 months and a history of excessive alcohol consumption in the last 5 years;
• Previous or planned liver transplant, bariatric surgery, ileal resection, or biliary diversion;
• History of acute cholecystitis and biliary obstructions (cholangitis);
• Recent (in the last 12 months) or concurrent use of agents known to cause hepatic steatosis (long-term systemic corticosteroids \[\>10 days\], amiodarone, methotrexate, tamoxifen, tetracyclines, high-dose estrogens, valproic acid);
• Recent (in the last 3 months) change in the dose/regimen or introduction of Vitamin E (at doses ≥400 IU/day), ursodeoxycholic acid (UDCA), betaine, S-adenosyl methionine, silymarin, or pentoxifylline;
• Presence of psychiatric disorders and/or diagnosis of any eating disorder;
• Life expectancy \<6 months.

Sponsors & Collaborators

• University of Bologna: lead

Study Sites (1)

IRCCS Azienda Ospedaliero-Universitaria di Bologna

Bologna, 40138, Italy

RECRUITING

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Obesity; Liver Cirrhosis

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Fibrosis; Pathologic Processes

Study Officials

• Fabio Piscaglia

  University of Bologna

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fabio Piscaglia, MD, PhD, Professor

CONTACT

0512142214; fabio.piscaglia@unibo.it

Federico Ravaioli, MD, PhD

CONTACT

+393333176759; f.ravaioli@unibo.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Two-arms, 2: 1 randomization stratified by type 2 diabetes mellitus and gender
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Multicentric, Prospective, Open, Randomized, Controlled, and Interventional, with no medicinal use

Study Record Dates

• First Submitted: February 19, 2024
• First Posted: March 13, 2024
• Study Start: September 29, 2021
• Primary Completion: November 24, 2024
• Study Completion (Estimated): December 12, 2026
• Last Updated: March 15, 2024

Record last verified: 2024-03

Locations

IT (1)