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

Trial Summary

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 data supports the idea that Nutritional Supplement for Hepatic Encephalopathy is an effective treatment?

The available research does not provide specific data on the effectiveness of Nutritional Supplement for Hepatic Encephalopathy. The studies focus on enteral nutrition for other conditions like intracerebral hemorrhage and head injuries, but they do not directly address hepatic encephalopathy. Therefore, there is no direct evidence from the provided information to support the effectiveness of this treatment for hepatic encephalopathy. ^{1 2 3 4 5}

What safety data exists for the nutritional supplement used in hepatic encephalopathy treatment?

The safety of L-ornithine-L-aspartate (LOLA) has been evaluated in clinical trials, including a randomized, double-blind, placebo-controlled trial and an open-label, prospective, multicentre observational study. These studies assessed its safety in controlling minimal hepatic encephalopathy and improving health-related quality of life in cirrhotic patients. Additionally, a pilot study tested the safety and tolerability of the probiotic Bacillus subtilis HU58 in patients with hepatic encephalopathy. These studies provide evidence of safety for these treatments in the context of hepatic encephalopathy. ^{6 7 8 9 10}

Is Ensure Enlive a promising treatment for hepatic encephalopathy?

The research articles provided do not specifically mention Ensure Enlive as a treatment for hepatic encephalopathy. They discuss other treatments like oral L-ornithine-L-aspartate, L-carnitine, lactulose, probiotics, and Bifidobacterium with fructo-oligosaccharides. Therefore, there is no direct evidence from these articles to suggest that Ensure Enlive is a promising treatment for hepatic encephalopathy. ^{6 11 12 13 14}

What is the purpose of this trial?

Readmission rates for patients with hepatic encephalopathy due to end stage liver disease are high. Hyperammonemia contributes significantly to encephalopathy and occurs because of impaired hepatic ureagenesis and increased skeletal muscle proteolysis. We propose a randomized, 6-month nutritional intervention in cirrhotic patients who have had at least 1 admission for hepatic encephalopathy within the last 6 months. We hypothesize that a combination of late evening and early morning protein supplement (Ensure Enlive) will decrease recurrent hepatic encephalopathy and consequent readmission rates by lowering skeletal muscle proteolysis and improved lean body mass.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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 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]

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 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]

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 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]

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]

References

1. Korea (South) pubmed.ncbi.nlm.nih.gov

Impact of early enteral nutrition on in-hospital mortality in patients with hypertensive intracerebral hemorrhage. [2021]

2. Japan 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. [2019]

3. United States 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. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Optimizing early enteral nutrition in severe stroke (OPENS): protocol for a multicentre randomized controlled trial. [2020]

5. England 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. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Oral l-ornithine-l-aspartate in minimal hepatic encephalopathy: A randomized, double-blind, placebo-controlled trial. [2022]

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

Identifying areas of improvement in nursing knowledge regarding hepatic encephalopathy management. [2021]

8. United States 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. [2022]

9. New Zealand 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. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Branched-chain amino acids for people with hepatic encephalopathy. [2022]

11. New Zealand 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. [2022]

12. Spain pubmed.ncbi.nlm.nih.gov

[Importance of nutritional support in patients with hepatic encephalopathy]. [2013]

13. England pubmed.ncbi.nlm.nih.gov

An open-label randomized controlled trial of lactulose and probiotics in the treatment of minimal hepatic encephalopathy. [2009]

14. England pubmed.ncbi.nlm.nih.gov

Bifidobacterium combined with fructo-oligosaccharide versus lactulose in the treatment of patients with hepatic encephalopathy. [2014]