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

ConditionsNASHNAFLDObesityLiver Fibrosis
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Bologna

About this trial

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).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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).

  • 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).

Treatment groups

42 Participants
are divided into 2 treatment groups
Group A: VLCKD armExperimental treatment 1 intervention
Group B: Control LCD armActive comparator 1 intervention

Trial outcomes

Primary outcomes

1

Change of at least one grade of liver fibrosis

Histological change of liver fibrosis without worsening of NASH

Time frame
12 months
2

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.

Time frame
12 months

Secondary outcomes

1

Histological NIH NASH CRN Score

Assessment of individual histological components that make up the NIH NASH CRN (NASH Clinical Research Network) Score. NAS (NAFLD Activity Score) is the unweighted sum of steatosis, lobular inflammation, and hepatocellular ballooning scores. NAS of ≥5 correlated with a diagnosis of NASH, and biopsies with scores of less than 3 were diagnosed as not NASH.

Time frame
12 months
2

Histological FLIP/SAF changes

Assessment of individual histological components that make up the FLIP (fatty liver inhibition of progression) SAF (steatosis activity fibrosis) score (based on steatosis, ballooning, lobular inflammation, fibrosis, etc.). The score ranges from 0 (not NAFLD) to 3 (NASH).

Time frame
12 months
3

Biochemical test changes 1

Evaluation of variation of the biochemical tests panel based on normal ranges provided by the local laboratory. Multiple parameters are included in biochemical panel: aspartate transaminase (AST). Normal range: \<50 U/L

Time frame
12 months
4

Biochemical test changes 2

Evaluation of variation of the biochemical tests panel based on normal ranges provided by the local laboratory. Multiple parameters are included in biochemical panel: alanine aminotransferase (ALT). Normal range: \<45 U/L

Time frame
12 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Bologna

Lead sponsor

Source ClinicalTrials.gov
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