Safety and Efficacy of Ketogenic Diet for Promoting Weight Loss in Obese Individuals With Compensated NASH Cirrhosis

Not Applicable

Active, not recruiting

Interventions: Other: Dietary consult for participants in the ketogenic diet arm
Other: Dietary consult for participants in the standard of care arm

Brief Summary: This is an open-label, randomized study comparing a monitored ketogenic diet intervention using standard ketogenic diet (SKD) and standard of care (SOC) dietary recommendations for 16 weeks. Subjects enrolled in the standard of care group will receive a voucher to Weight Watchers after study completion.

Detailed Description: The primary aim is to assess the safety of ketogenic diet as compared to standard of care approach for weight loss in patients with compensated cirrhosis due to NASH. The safety endpoints captured in the study include liver decompensation events, measured through several questionnaires, fasting blood glucose, serum creatinine, fasting lipid profile and other adverse events. The tolerability of the ketogenic diet will be assessed by study compliance and by administering a questionnaire.

Secondary aims include weight loss, changes in body composition via serial use of bioelectrical impedance via an Inbody Machine, changes in liver fat and liver stiffness using MRI and proton density fat fraction (MRI-PDFF), liver biochemistries, changes in Child-Turcotte-Pugh and MELD scores measured via labs and changes in liver steatosis and stiffness via serial measures of VCTE by FibroScan®.

Recruitment & Eligibility

Inclusion Criteria

Exclusion Criteria

Actively participation in investigational drug treatment for non-alcoholic fatty liver disease
Currently taking medications for weight loss or have joined a supervised weight loss program prior to enrollment
Have hepatocellular carcinoma and are undergoing therapy
Women who become pregnant or plan to become pregnant prior to the study date; female subjects who become pregnant during the study will be withdrawn from the study
Pacemaker or implantable cardioverter devices
History of hepatic surgery
Current significant alcohol consumption, defined as more than 20 grams per day in females or 30 grams per day in males
Presence of ascites or hepatic encephalopathy
Symptomatic gastroparesis
Uncontrolled diabetes, as defined by a HgbA1C >11%
Uncontrolled congestive heart failure
Active infections
Child Turcotte Pugh score > 6
MELD score >12
Unwilling to undergo an MRI or have contraindications to an MRI

Arm && Interventions

Group	Intervention	Description
Ketogenic diet	Dietary consult for participants in the ketogenic diet arm	For participants randomized to the ketogenic diet arm, a consultation with the providers of medically supervised weight loss clinic of Indiana University Health will be arranged. Subjects will be educated on the concepts of ketosis, symptoms associated with it, and dietary manipulation to achieve ketosis. Participants in this arm will use the suggested recipes in combination with strict carbohydrate monitoring though checking for urine ketone bodies. These recipes were gathered and vetted by the dietitian at the medically supervised weight loss clinic. We anticipate that this approach will allow for more calorie intake and easier carbohydrate restriction. The follow up visits will be determined by the providers of the medically supervised weight loss clinic based on the symptoms reported and subject's compliance with carbohydrate restriction.
Standard of Care	Dietary consult for participants in the standard of care arm	For participants randomized to this arm, a consultation with the providers of medically supervised weight loss clinic will be arranged. The discussion will focus on portion control using a balanced diet. A follow up visit will be at 16 weeks. This is the extent of interventions received for participants in this arm.

Primary Outcome Measures

Name	Time	Method
Blood chemistry to assess for liver de-compensation events	Blood chemistry tests will be assessed at the Week 16 visit.	Blood will be drawn serially to assess fasting blood glucose, serum creatinine and fasting lipid profile.
Adverse events	All participants will be monitored at the week 16 visit and all participants will be instructed to alert the study team for additional information if such an event occurs.	All participants will be monitored for adverse events and/or serious adverse events throughout the duration of the trial.
Tolerability of the ketogenic diet	The POMS 40 questionnaire is administered at the Week 16 visit.	How well the ketogenic diets is tolerated will be assessed by administering a POMS40 questionnaire.

Secondary Outcome Measures

Name	Time	Method
MRI with proton density fat fraction (PDFF)	Performed at initial visit and at week 16 visit	MRI-PDFF is a convenient method for liver fat quantification and currently used in most clinical trials, as it only requires a single 20-second breath hold and an estimated time of about 5 minutes in an MRI scanner suite. MRI in the study will be used to quantify liver steatosis, stiffness, and body composition.
Changes in liver stiffness and steatosis	Performed at initial visit and at week 16 visit	Changes in liver stiffness and steatosis will be measured with serial use of vibration controlled transient elastography (VCTE) via a FibroScan.
Weight loss and change in body composition	Performed at initial visit and at week 16 visit	Changes in weight and body composition will be measured via serial use of a scale and use of bioelectrical impedance via an Inbody machine

Locations (1): Indiana University School of Medicine
🇺🇸
Indianapolis, Indiana, United States