Nutritional Supplement for Hepatic Encephalopathy

Overseen By Annette C Bellar

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: The Cleveland Clinic

Must not be taking: Anabolic steroids, Corticosteroids

Disqualifiers: MELD score > 35, Organ failure, Kidney injury, Active malignancy, Uncontrolled diabetes, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the nutritional supplement Ensure Enlive to determine if it can help people with hepatic encephalopathy (confusion caused by liver disease) reduce their hospital visits. The trial aims to discover whether taking this supplement at night and in the morning can improve muscle health and lower the chance of the condition recurring. People with cirrhosis (severe liver scarring) who have been hospitalized for hepatic encephalopathy in the past year might be suitable candidates for this trial. As an unphased trial, this study offers a unique opportunity to explore the potential benefits of Ensure Enlive for liver health.

Do I need to stop my current medications for this trial?

The trial does not specify if you need to stop your current medications, but you cannot participate if you are taking anabolic steroids or corticosteroids.

What prior data suggests that Ensure Enlive is safe for patients with hepatic encephalopathy?

Research shows that Ensure Enlive is generally easy for most people to tolerate. This nutritional drink provides important proteins and energy. Studies indicate that supplements like Ensure Enlive do not increase the risk of conditions such as hepatic encephalopathy, which affects brain function due to liver problems. This suggests the supplement is safe for people with liver disease.

Other studies have shown that nutritional supplements can boost energy and protein intake without causing major side effects. Although specific data on Ensure Enlive for hepatic encephalopathy is limited, the supplement is widely used and known for its safety in similar situations.

Overall, available research supports Ensure Enlive as a safe choice for those considering joining this study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Ensure Enlive is unique because it offers a nutritional approach to managing hepatic encephalopathy, a condition that typically relies on medications like lactulose and rifaximin to reduce toxins in the blood. Unlike these drugs, Ensure Enlive provides essential nutrients and proteins that may help improve liver function and brain health. Researchers are excited about this treatment because it could offer a simpler, non-pharmaceutical option that supports overall health and potentially enhances quality of life for patients without the side effects associated with traditional medications.

What evidence suggests that Ensure Enlive might be an effective treatment for hepatic encephalopathy?

Studies have shown that nutritional support can greatly benefit individuals with liver issues such as hepatic encephalopathy. Research indicates that feeding through the gut, known as enteral nutrition, provides sufficient energy and protein without complications. In some cases, it matches the effectiveness of steroids. Nutritional counseling has been found to reduce death rates and prevent severe episodes of hepatic encephalopathy, a serious brain condition caused by liver disease. In this trial, participants will receive either the protein supplement Ensure Enlive or standard care. Ensure Enlive may help by reducing muscle breakdown and improving muscle mass, potentially lowering hospital readmission rates for these patients. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults with cirrhosis who've been hospitalized for hepatic encephalopathy in the last year. They must have a diagnosis confirmed by clinical history, liver biopsy, or imaging and not be severely ill (MELD score ≤ 35), have uncontrolled diabetes (A1c ≤ 9.5), recent GI bleeding or surgery, active cancer, significant kidney injury, end-stage organ failure, or be on muscle-affecting drugs.

Inclusion Criteria

I have been diagnosed with cirrhosis through tests or my medical history.

I was hospitalized for HE within the last year.

You have had an abdominal CT scan before.

Exclusion Criteria

Your MELD score is higher than 35.

You currently have an infection with positive test results in your blood or other body fluids.

I am currently experiencing bleeding in my digestive tract.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a 6-month nutritional intervention with late evening and early morning protein supplements

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ensure Enlive

Trial Overview The study tests if taking Ensure Enlive protein supplement late at night and early morning can reduce hospital readmissions due to hepatic encephalopathy in cirrhotic patients. It's a randomized trial comparing this nutritional intervention against standard care over six months.

How Is the Trial Designed?

Group I: Ensure Enlive Active Control 2 Interventions

Group II: Standard of Care Placebo Group 1 Intervention

Ensure Enlive is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Ensure Enlive for:

• Nutritional support for patients with malnutrition, including those with liver disease

Approved in European Union as Ensure Enlive for:

• Nutritional support for patients with malnutrition, including those with liver disease

Approved in Canada as Ensure Enlive for:

• Nutritional support for patients with malnutrition, including those with liver disease

Who Is Running the Clinical Trial?

The Cleveland Clinic

Lead Sponsor

Trials

1,072

Recruited

1,377,000+

Published Research Related to This Trial

In a study of 64 cirrhotic outpatients with minimal hepatic encephalopathy (MHE), oral l-ornithine-l-aspartate (LOLA) did not show significant improvement over placebo in treating MHE symptoms, but it did lead to a notable reduction in episodes of overt hepatic encephalopathy (OHE) over a 6-month follow-up period (5% in LOLA group vs 37.9% in placebo).

LOLA treatment resulted in significant improvements in specific psychometric tests (NCT-B and CFF), indicating some cognitive benefits, while no serious adverse effects were reported, suggesting it is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral l-ornithine-l-aspartate in minimal hepatic encephalopathy: A randomized, double-blind, placebo-controlled trial. Alvares-da-Silva, MR., de Araujo, A., Vicenzi, JR., et al.[2022]

In a study of 31 patients with hepatic cirrhosis, L-carnitine significantly reduced serum ammonia levels, with 14 out of 16 patients achieving normal ammonia levels after 4 weeks of treatment.

L-carnitine also led to improvements in neuropsychological performance, as indicated by psychometric tests, with no significant adverse effects reported, suggesting it is a safe and effective option for managing subclinical hepatic encephalopathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of L-carnitine in reducing hyperammonaemia and improving neuropsychological test performance in patients with hepatic cirrhosis : results of a randomised trial. Cecere, A., Ciaramella, F., Tancredi, L., et al.[2022]

In a study of 190 cirrhotic patients, 55.2% were diagnosed with minimal hepatic encephalopathy (MHE), highlighting its prevalence in this population.

Treatment with lactulose, probiotics, or a combination of both showed similar efficacy in improving cognitive function and reducing venous ammonia levels in patients with MHE, with around 54-57% of patients normalizing their test results after one month of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open-label randomized controlled trial of lactulose and probiotics in the treatment of minimal hepatic encephalopathy. Sharma, P., Sharma, BC., Puri, V., et al.[2009]

The probiotic Bacillus subtilis HU58 was found to be safe and well tolerated in a 4-week pilot study involving 40 patients with hepatic encephalopathy, with no severe treatment-emergent adverse events reported.

Patients with higher baseline blood ammonia levels (>60 μg/dL) showed a significant reduction in blood ammonia levels when treated with B. subtilis HU58, suggesting potential benefits for this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Oral Formulation of the Probiotic, Bacillus subtilis HU58, Was Safe and Well Tolerated in a Pilot Study of Patients with Hepatic Encephalopathy. Yossef, S., Clark, F., Bubeck, SS., et al.[2022]

In a study of 123 patients with critical hypertensive intracerebral hemorrhage, early enteral nutrition (initiated within 48 hours) significantly reduced in-hospital mortality (10.1% vs. 35.3% for delayed nutrition) and the incidence of nosocomial pneumonia.

Early enteral nutrition was identified as an independent predictor of better outcomes, suggesting that starting nutrition early can improve recovery and reduce complications in critically ill patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of early enteral nutrition on in-hospital mortality in patients with hypertensive intracerebral hemorrhage. Lee, JS., Jwa, CS., Yi, HJ., et al.[2021]

Protein calorie malnutrition is common in patients with chronic liver disease and negatively impacts their prognosis, as it is linked to increased caloric needs due to a hypermetabolic state.

Restricting dietary protein to manage hepatic encephalopathy may not be beneficial and can worsen nutritional status; instead, treatments like branched-chain amino acids and probiotics may offer better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Importance of nutritional support in patients with hepatic encephalopathy]. Jurado García, J., Costán Rodero, G., Calañas-Continente, A.[2013]

In a study involving 125 patients with hepatic encephalopathy, treatment with Bifidobacterium and fructo-oligosaccharides (FOS) significantly improved cognitive function and reduced blood ammonia levels compared to lactulose after 60 days.

Bifidobacterium+FOS treatment led to better performance on psychometric tests, indicating its potential as an effective alternative to lactulose for managing hepatic encephalopathy in cirrhosis patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bifidobacterium combined with fructo-oligosaccharide versus lactulose in the treatment of patients with hepatic encephalopathy. Malaguarnera, M., Gargante, MP., Malaguarnera, G., et al.[2014]

A survey of 169 nurses revealed significant knowledge gaps regarding hepatic encephalopathy (HE), with over 30% unaware that ammonia is a key toxin involved in its development.

The survey also highlighted a need for better dietary education, as 80% of nurses incorrectly believed that fat and carbohydrate intake should be restricted for patients with HE, indicating a potential area for improvement in patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identifying areas of improvement in nursing knowledge regarding hepatic encephalopathy management. Sohal, A., Green, V., Sandhu, S., et al.[2021]

Branched-chain amino acids (BCAA) have a significant beneficial effect on hepatic encephalopathy, reducing symptoms in patients, with high-quality evidence from 16 trials involving 827 participants.

However, BCAA did not show any impact on mortality rates or quality of life, and they increased the risk of nausea and vomiting, indicating a need for further research to fully understand their effects and safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Branched-chain amino acids for people with hepatic encephalopathy. Gluud, LL., Dam, G., Les, I., et al.[2022]

In a study of 50 patients with neurological diseases receiving long-term enteral nutrition (EN) for at least one year, the fatty acid composition of the EN formulas significantly influenced serum levels of essential fatty acids like EPA and DHA.

Formulas enriched with alpha-linolenic acid (ALA) and lower in linoleic acid (LA) improved EPA and DHA levels, but only formulas containing preformed EPA and DHA achieved normal serum levels, suggesting that the right fatty acid composition is crucial for optimal fatty acid status in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The nutrient formula containing eicosapentaenoic acid and docosahexaenoic acid benefits the fatty acid status of patients receiving long-term enteral nutrition. Munakata, M., Nishikawa, M., Togashi, N., et al.[2019]

In a study of 82 head-injured patients requiring mechanical ventilation, early enhanced enteral nutrition (EN) led to a higher percentage of energy and nitrogen requirements being met in the first week, which may support better recovery outcomes.

Patients receiving enhanced EN showed a trend towards improved neurologic outcomes at 3 months and significantly fewer complications, including a lower incidence of infections and overall complications, compared to those receiving standard EN.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective, randomized, controlled trial to determine the effect of early enhanced enteral nutrition on clinical outcome in mechanically ventilated patients suffering head injury. Taylor, SJ., Fettes, SB., Jewkes, C., et al.[2022]

The OPENS trial will involve 600 adult patients with severe stroke across 12 sites in China, comparing three feeding strategies: standard full enteral nutrition, modified full enteral nutrition with a prokinetic drug, and permissive underfeeding.

The primary goal is to determine which feeding strategy leads to better outcomes at 90 days post-enrollment, addressing a significant gap in knowledge regarding nutritional management in critically ill stroke patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing early enteral nutrition in severe stroke (OPENS): protocol for a multicentre randomized controlled trial. Yuan, F., Yang, F., Zhang, W., et al.[2020]

A randomized controlled trial is being conducted with 220 patients who have traumatic intracerebral hemorrhage to compare the effects of early low-energy enteral nutrition (10 kcal/kg/day) versus high-energy enteral nutrition (25 kcal/kg/day) over 7 days.

The primary goal of the study is to determine if low-energy nutrition can reduce 90-day mortality and feeding-related complications while improving neurological outcomes, with safety monitored daily during hospitalization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early low-energy versus high-energy enteral nutrition support in patients with traumatic intracerebral haemorrhage: protocol for a randomised controlled trial. Shen, Y., Cheng, X., Ying, M., et al.[2022]

In a study of 191 cirrhotic patients with hepatic encephalopathy, treatment with L-ornithine-L-aspartate for 8 weeks significantly improved health-related quality of life (HR-QOL), particularly in areas like fatigue, sleep quality, and concentration.

The treatment was well tolerated, with 97.8% of patients reporting very good or good tolerability and no drug-related adverse events, indicating its safety for use in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral L-ornithine-L-aspartate improves health-related quality of life in cirrhotic patients with hepatic encephalopathy: an open-label, prospective, multicentre observational study. Ong, JP., Oehler, G., Krüger-Jansen, C., et al.[2021]

Citations

1. withpower.com withpower.com/trial/nutritional-supplement-for-hepatic-encephalopathy-fe8e6

Nutritional Supplement for Hepatic Encephalopathy Trial Overview The study tests if taking Ensure Enlive protein supplement late at night and early morning can reduce hospital readmissions due to hepatic ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6823271/

Nutritional support for liver disease - PMC - PubMed Central These were that 1) parenteral nutrition reduced serum bilirubin more rapidly and improved one type of nutritional outcome (nitrogen balance) in medical patients ...

3. clinicalnutritionjournal.com clinicalnutritionjournal.com/article/S0261-5614(06)00038-0/fulltext

ESPEN Guidelines on Enteral Nutrition: Liver disease EN ensures adequate energy and protein intake without the risk of complications such as hepatic encephalopathy (Ib). EN was as effective as steroids in patients ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10987054/

Future Therapies of Hepatic Encephalopathy - PMC Lactobacillus supplementation, specifically, has been repeatedly demonstrated to be effective at reducing ammonia levels and improving cognitive function, ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/hepr.14053

Nutritional counseling improves mortality and prevents ... Our findings show that nutritional counseling is effective in reducing mortality rates and in preventing overt hepatic encephalopathy and ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03285217

HMB for Denutrition in Patients With Cirrhosis (HEPATIC) This study aims to translate those beneficial effects to cirrhotic patients. The investigators hypothesize that HMB can improve cirrhosis-related metabolic ...