Ketogenic Diet for NASH Cirrhosis Weight Loss

Overseen By Emily Smith, BS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Indiana University

Must not be taking: Weight loss drugs

Disqualifiers: Hepatocellular carcinoma, Pregnancy, Alcohol use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 16

Duration: 16 weeks

40 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on weight loss medications or in a supervised weight loss program before joining.

What data supports the effectiveness of the ketogenic diet as a treatment for NASH cirrhosis weight loss?

Research shows that a ketogenic diet, which is high in fat and low in carbohydrates, can help reduce liver fat and improve liver health in people with nonalcoholic fatty liver disease (NAFLD), a condition related to NASH. Studies have found that this diet can lead to significant weight loss and improvements in liver function markers. ^{1 2 3 4 5}

Is the ketogenic diet safe for humans?

Research suggests that ketogenic diets, which are low in carbohydrates and high in fats, are generally safe for weight loss and improving certain health markers, like triglyceride levels, in humans. ^{1 4 6 7 8}

How does the ketogenic diet treatment for NASH cirrhosis differ from other treatments?

The ketogenic diet is unique for NASH cirrhosis as it focuses on a high-fat, low-carbohydrate intake, which can lead to significant weight loss and reduction in liver fat, unlike other diets that may not achieve the necessary weight loss to improve NASH severity. This diet also potentially reduces liver inflammation and fibrosis, offering a novel approach compared to traditional low-fat diets. ^{1 2 3 4 9}

Research Team

Raj Vuppalanchi, MD

Principal Investigator

Indiana University

Eligibility Criteria

This trial is for obese individuals with a BMI over 30 who have NASH cirrhosis but no other major health issues like uncontrolled diabetes, significant alcohol consumption, or heart failure. It's not for those on weight loss drugs, in another fatty liver disease study, or with devices like pacemakers.

Inclusion Criteria

I am 18 years old or older.

I have NASH cirrhosis and my BMI is over 30.

Exclusion Criteria

Having a pacemaker or implantable cardioverter devices

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

MELD score >12

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants follow a ketogenic diet or standard of care dietary recommendations for 16 weeks

16 weeks

Initial visit, follow-up at week 16

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Ketogenic Diet

Trial Overview The study compares the effects of a ketogenic diet (SKD) to standard dietary care (SOC) over 16 weeks in promoting weight loss among participants. Those in the SOC group will get a Weight Watchers voucher after completing the study.

Participant Groups

Group I: Ketogenic diet Active Control 1 Intervention

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.

Group II: Standard of Care Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

Indiana University

Lead Sponsor

Trials

1,063

Recruited

1,182,000+

Findings from Research

In a pilot study of 5 patients with obesity-related fatty liver disease, a low-carbohydrate ketogenic diet for 6 months resulted in an average weight loss of 12.8 kg, indicating its potential effectiveness for weight management.

Post-treatment liver biopsies showed significant histological improvements in liver fat content, inflammation, and fibrosis, suggesting that this dietary approach may help reverse fatty liver disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of a low-carbohydrate, ketogenic diet on nonalcoholic fatty liver disease: a pilot study. Tendler, D., Lin, S., Yancy, WS., et al.[2018]

A systematic review of three trials involving 128 adults with non-alcoholic fatty liver disease (NAFLD) found that specific dietary patterns, particularly the Mediterranean diet, can significantly reduce hepatic fat content and triglyceride levels.

The Mediterranean diet showed strong evidence of reducing hepatic fat by 4.1% and triglycerides by 16.9 mg/dL compared to low-fat diets, highlighting its potential as an effective lifestyle modification for managing NAFLD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of dietary patterns on non-alcoholic fatty liver disease diagnosed by biopsy or magnetic resonance in adults: a systematic review of randomised controlled trials. Angelidi, AM., Papadaki, A., Nolen-Doerr, E., et al.[2022]

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing alongside obesity and metabolic syndrome, making it the most common chronic liver disease, which can progress to severe conditions like cirrhosis and liver cancer.

A ketogenic diet (KD), which is very low in carbohydrates, may help alleviate oxidative stress and restore mitochondrial function, suggesting it could be a potential therapeutic approach for managing NAFLD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigating the Link between Ketogenic Diet, NAFLD, Mitochondria, and Oxidative Stress: A Narrative Review. Paoli, A., Cerullo, G.[2023]

The Spanish Ketogenic Mediterranean Diet (SKMD) significantly improved various health markers in 14 obese men over 12 weeks, including body weight, liver enzymes, and cholesterol levels, indicating its efficacy in treating metabolic syndrome (MS) and nonalcoholic fatty liver disease (NAFLD).

After following the SKMD, all participants were free of metabolic syndrome according to the International Diabetes Federation criteria, demonstrating the diet's potential as a safe and effective intervention for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of the Spanish Ketogenic Mediterranean Diet on nonalcoholic fatty liver disease: a pilot study. Pérez-Guisado, J., Muñoz-Serrano, A.[2017]

Ketogenic diets, which are low in carbohydrates and high in fats, have been shown to be effective for weight loss and can improve triglyceride and HDL cholesterol levels compared to low-fat diets.

Despite concerns about their high fat content, the degree of carbohydrate restriction needed to achieve ketosis is still unclear, indicating a need for more standardized research on these diets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketogenic diets for weight loss: A review of their principles, safety and efficacy. Sumithran, P., Proietto, J.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

The effect of a low-carbohydrate, ketogenic diet on nonalcoholic fatty liver disease: a pilot study. [2018]

2. Switzerland pubmed.ncbi.nlm.nih.gov

The Effects of Eight Weeks' Very Low-Calorie Ketogenic Diet (VLCKD) on Liver Health in Subjects Affected by Overweight and Obesity. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Comparison of Ketogenic Diets with and without Ketone Salts versus a Low-Fat Diet: Liver Fat Responses in Overweight Adults. [2021]

4. Poland pubmed.ncbi.nlm.nih.gov

Ketogenic, Hypocaloric Diet Improves Nonalcoholic Steatohepatitis. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

The effect of dietary patterns on non-alcoholic fatty liver disease diagnosed by biopsy or magnetic resonance in adults: a systematic review of randomised controlled trials. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Investigating the Link between Ketogenic Diet, NAFLD, Mitochondria, and Oxidative Stress: A Narrative Review. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

The effect of the Spanish Ketogenic Mediterranean Diet on nonalcoholic fatty liver disease: a pilot study. [2017]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Ketogenic diets for weight loss: A review of their principles, safety and efficacy. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of an Eight Week Very Low-Calorie Ketogenic Diet (VLCKD) on White Blood Cell and Platelet Counts in Relation to Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in Subjects with Overweight and Obesity. [2023]