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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a ketogenic diet might aid weight loss for individuals with NASH cirrhosis, a liver condition linked to obesity. Participants will either follow a ketogenic diet, low in carbohydrates and designed to encourage fat burning for energy, or receive standard dietary advice. Those in the standard care group will receive a Weight Watchers voucher after the trial. The trial seeks individuals with both NASH cirrhosis and obesity (body mass index over 30) who are not currently in a weight loss program or taking weight loss medications. As an unphased trial, this study provides a unique opportunity to enhance understanding of dietary impacts on liver health and weight management.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the ketogenic diet is generally safe and can benefit liver health. It may aid in weight loss and improve liver function without causing harm. One study found that a low-carb diet, like the ketogenic diet, did not harm liver health over six weeks. Another study demonstrated that this diet can reduce liver fat and help the body use food for energy more efficiently.

However, some animal studies suggest that the ketogenic diet might cause liver problems, such as fibrosis, which is the thickening and scarring of liver tissue, even with weight loss. These studies involved mice, so the results might not apply to humans.

In summary, while many studies support the safety of the ketogenic diet, some research indicates possible risks. Participants should consider these findings and consult their healthcare provider before joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike standard treatments for NASH cirrhosis, which typically focus on balanced diets and portion control, the ketogenic diet is unique because it shifts the body's metabolism to burn fat instead of carbohydrates. This diet induces a state called ketosis, where the body uses ketones for energy, potentially leading to more effective weight loss. Researchers are excited about this approach because it might offer a more efficient way to manage weight and restrict carbohydrates, potentially improving liver health in a way that traditional diets do not.

What evidence suggests that the ketogenic diet might be an effective treatment for NASH cirrhosis?

Research has shown that a ketogenic diet, which participants in this trial may receive, can aid individuals with nonalcoholic fatty liver disease in losing weight and improving overall health. Studies have found that losing more than 5% of body weight can reduce liver fat, with even better results at a 10% weight loss. This diet can also enhance the body's insulin use. In a small study, individuals with obesity-related fatty liver disease lost a noticeable amount of weight on a low-carb ketogenic diet over six months. Overall, the ketogenic diet appears promising for reducing liver fat and improving liver health. ^{1 2 3 4 6}

Who Is on the Research Team?

Raj Vuppalanchi, MD

Principal Investigator

Indiana University

Are You a Good Fit for This Trial?

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7227162/

Ketogenic, Hypocaloric Diet Improves Nonalcoholic ...

In summary, our data suggest that a hypocaloric, ketogenic diet can bring about significant weight loss and improvements in metabolic syndrome ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11355934/

Beneficial Effects of the Ketogenic Diet on Nonalcoholic ...

Reduction in body weight by only >5% results in a detectable alleviation of fatty liver degeneration, while ≥10% provides the best effects including, among ...

3.

sciencedirect.com

sciencedirect.com/science/article/pii/S2212877823000091

A low-carbohydrate diet induces hepatic insulin resistance ...

Results. We demonstrate that KD can induce fibrosis and NASH regardless of body weight loss compared to high-fat diet (HFD) fed mice at thermoneutrality.

4.

mdpi.com

mdpi.com/2072-6643/17/7/1269

Ketogenic Diet in Steatotic Liver Disease: A Metabolic ...

The analysis indicates that ketogenic diets significantly reduce hepatic fat content and improve metabolic parameters, including insulin sensitivity and liver ...

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withpower.com

withpower.com/trial/phase-fibrosis-7-2020-18ad2

Ketogenic Diet for NASH Cirrhosis Weight Loss

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 ...

6.

sciencedirect.com

sciencedirect.com/science/article/pii/S0261561424001353

Ketogenic diet time-dependently prevents NAFLD through ...

KD prevents NAFLD phenotype in a time-dependent manner. Two weeks of KD feeding is the optimal time point for alleviating NAFLD.