Nutritional Supplement for Hepatic Encephalopathy

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

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

Trial Summary

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.

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}

Research Team

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 am 18 years old or older.

I was hospitalized for HE within the last year.

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.

Trial 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 (Dietary Supplement)

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Cleveland Clinic Foundation Cleveland, OH

Who Is Running the Clinical Trial?

The Cleveland Clinic

Lead Sponsor

Trials

1072

Patients Recruited

1,377,000+

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] We conducted this study to evaluate the clinical impact of early enteral nutrition (EN) on in-hospital mortality and outcome in patients with critical hypertensive intracerebral hemorrhage (ICH).

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] Currently, various formulas with different fatty acid compositions are used for enteral nutrition (EN). All formulas contain various concentrations of essential fatty acids: linoleic acid (LA) and alpha-linolenic acid (ALA); LA is biotransformed into arachidonic acid (AA) and ALA into eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in vivo. Some formulas contain preformed EPA and DHA. However, the effects of the differences in the fatty acid composition on the fatty acid status of patients receiving long-term EN is not clear. We measured serum fatty acid concentrations in 50 patients with neurological diseases receiving long-term EN. The data were then compared retrospectively with reference to the fatty acid compositions of the formulas used. All of the patients received almost their entire nutritional intake via EN for at least 1 year. Blood samples were obtained just before injecting the EN solution. Among the formulas that did not include EPA or DHA, formulas with low ALA concentrations were associated with low serum EPA and DHA. Conversely, the ALA-enriched formulas with reduced LA concentrations significantly increased EPA and DHA levels, although the levels remained lower than the control values. With the formula containing EPA and DHA, the EPA and DHA levels reached control values. Therefore, the fatty acid composition of the EN formulas affected the fatty acid status of patients receiving long-term EN. Formulas containing preformed EPA and DHA with suitable amounts of essential fatty acids may benefit these patients.

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] To determine the effect of early enhanced enteral nutrition (EN) on clinical outcome of head-injured patients.

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

Optimizing early enteral nutrition in severe stroke (OPENS): protocol for a multicentre randomized controlled trial. [2020] Malnutrition is one of the crucial factors associated with poor prognosis in critical ill patients, yet a significant evidence gap surrounds the management of initial enteral feeding in severe stroke. The Optimizing Early Enteral Nutrition in Severe Stroke (OPENS) trial will compare a strategy of modified full enteral nutrition (EN) (standard full EN in conjunction with prokinetic drug) and a strategy of permissive underfeeding (40 to 60% of estimated caloric requirements) with standard full EN (advancement to target nutrition goals) in patients with severe stroke.

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] Early enteral nutrition (EN) is associated with shorter hospital stay and lower infection and mortality rates in patients with intracerebral haemorrhage. However, high-energy support always causes clinical complications, such as diarrhoea and aspiration pneumonia, and the true benefit of high-energy support in these patients has not been investigated. The appropriate amount of energy support still needs further investigation. Therefore, we are performing a randomised controlled trial to investigate whether early low-energy EN can decrease mortality and feeding-related complications and improve neurological outcomes as compared with high-energy EN in traumatic intracerebral haemorrhage (TICH) patients.

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

Oral l-ornithine-l-aspartate in minimal hepatic encephalopathy: A randomized, double-blind, placebo-controlled trial. [2022] Evaluate efficacy/safety of oral l-ornithine-l-aspartate (LOLA) in controlling minimal hepatic encephalopathy (MHE).

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

Identifying areas of improvement in nursing knowledge regarding hepatic encephalopathy management. [2021] Hepatic encephalopathy (HE) is a reversible brain dysfunction caused by liver insufficiency and portosystemic shunting. Hepatic encephalopathy is a common complication of advanced liver disease and is on a rise with the increasing incidence of non-alcoholic steatohepatitis (NASH). Since partnership with nursing staff is a critical part of successful management of these complex patients, we conducted a survey assessing their knowledge regarding HE.169 nurses participated in the survey. We found that more than 30% of the nurses did not know that ammonia is one of the toxins responsible for causing hepatic encephalopathy. We also found that 20% of the nurses had difficulty answering questions regarding titration of lactulose to bowel movements. Dietary education is a significant area for improvement as 80% of the nurses wanted to restrict fat and carbohydrate intake in these patients. With this simple survey, we identified important knowledge gaps among experienced nurses at our institution. We believe that by improving knowledge through focused lectures, we can improve patient care and reduce the length of hospitalizations in patients with HE.

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] Label="BACKGROUND" NlmCategory="BACKGROUND">Hepatic encephalopathy often results in high blood ammonia levels because of inefficient ammonia processing by the liver. Lactulose treatment promotes the growth of urease-producing gut bacteria and a reduced colon pH, thus reducing blood ammonia absorption. It is thought that probiotics as an add-on therapy may be beneficial. Patients and Methods. Bacillus subtilis HU58 was tested for safety and tolerability in patients with hepatic encephalopathy taking lactulose in this double-bind, placebo-controlled, 4-week pilot study. Study participants received one dose of B. subtilis HU58 or placebo (orally) for the first five days and two daily doses thereafter. Participants were monitored for safety and blood ammonia levels.

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] Hepatic encephalopathy (HE) is a serious complication of cirrhosis. Clinical trials have consistently shown that L-ornithine-L-aspartate significantly improves HE symptoms. Health-related quality of life (HR-QOL) is impaired in HE patients and represents an important outcome measure for therapeutic intervention. The present study aimed to assess the impact of L-ornithine-L-aspartate on HR-QOL and safety in patients with HE in a clinical practice setting.

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

Branched-chain amino acids for people with hepatic encephalopathy. [2022] Hepatic encephalopathy is a brain dysfunction with neurological and psychiatric changes associated with liver insufficiency or portal-systemic shunting. The severity ranges from minor symptoms to coma. A Cochrane systematic review including 11 randomised clinical trials on branched-chain amino acids (BCAA) versus control interventions has evaluated if BCAA may benefit people with hepatic encephalopathy.

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] To determine the efficacy of L-carnitine in reducing hyperammonaemia and improving neuropsychological performance in patients with hepatic cirrhosis and subclinical hepatic encephalopathy (SHE).

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

[Importance of nutritional support in patients with hepatic encephalopathy]. [2013] Protein calorie malnutrition is frequently a complication in the chronic liver disease patient and is considered to be a negative prognostic factor. Anorexia and several other endocrine metabolic complications produce an hypermetabolic state that needs more caloric intake. Hepatic encephalopathy is one of the developments possible in patients with descompensated cirrhosis. The wellknown role of ammonia in the pathogenesis of hepatic encephalopathy has determined a restriction in dietary protein along many decades. Nevertheless, there is no evidence about a low protein diet being better in the outcome of hepatic encephalopathy, it worsens, moreover, the nutritional status and helps in the development of many nutritional related complications. This article reviews the use of oral branched-chain amino acids and proteins of different sources, probiotics, synbiotics, antioxidants, oral L-Ornithine L-Aspartate and acetyl-L-carnitine in patients with hepatic encephalopathy.

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] Minimal hepatic encephalopathy (MHE) is associated with poor quality of life and increased work disability. Treatment with lactulose and probiotics has shown some benefit. We compared lactulose with probiotics and a combination of lactulose plus probiotics in the treatment of MHE.

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

Bifidobacterium combined with fructo-oligosaccharide versus lactulose in the treatment of patients with hepatic encephalopathy. [2014] Hepatic encephalopathy (HE) is a reversible neuropsychiatric syndrome in patients with liver disease. It was suggested that Bifidobacterium+fructo-oligosaccharides (FOS) may decrease blood and brain ammonia levels.