Effect of Brief Dietary Intervention on Ammonia Levels

Study Overview
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Brief Summary
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Study the impact of differing meal contents on venous ammonia levels over time in patients with cirrhosis. Patients will be given specific meals and venous ammonia analyzed over time after those meals. The subjects will also provide stool for microbiome and serum, urine and plasma for metabolomics during this one-time study. Total duration=4 hours

Detailed Description
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Patient will be instructed to collect stool for baseline assessments. After a fast (>4h from last meal) a venous blood sample will be drawn for analysis of baseline laboratory tests and spot venous ammonia and blood and urine for metabolomics and blood microbiome. Spot ammonia and blood for metabolomics and microbiome will be collected from repeat samples at 1h and 2 hrs after a standardized meals from the three groups of protein meals. Urine will also be collected for metabolomics during the observation period. On the day of the study, patients will be asked to complete a standard food frequency questionnaire encompassing meals over 3 days prior to the study. Subjects will be randomly assigned into 3 groups (meal types A, B and C) with the standardized meal that contains 20gm of protein. All subjects are expected to consume it in its entirety. Subjects are not allowed to eat anything else until the end of the study. Subjects will be observed in the unit for a total of 3 hours after the standardized meal to ensure no symptoms related to potential elevated ammonia emerge. Any adverse events will be treated according to standard clinical routine.

Official Title
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Characterization of Venous Ammonia Levels in Fasted and Fed State in Patients With Cirrhosis After Vegetarian, Vegan and Non-Vegetarian Meals

Conditions
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Cirrhosis, Hepatic Encephalopathy

Intervention / Treatment
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* Other: One meal


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cirrhosis Able and willing to voluntarily complete the informed consent process Available for and agree to all study procedures Consistent non-vegetarian Western dietary patterns for at least a month prior to the study assessed by dietary interview Exclusion Criteria: MELD score > 23 Unclear diagnosis of cirrhosis History of liver transplant Body mass index < 18.5 or ≥ 40 kg/m2 Prior transjugular intrahepatic portosystemic shunt placement Treatment with systemic (e.g., oral or intravenous) antibiotic (apart from rifaximin) within 4 weeks prior to enrollment For those with HE: stable dose of medications (lactulose or rifaximin) without a recent (<1 month episode of HE) Current use of valproate, corticosteroids, or cytotoxic drugs. Apart from chronic liver disease, any acute or chronic medical, surgical, psychiatric, or social condition including history of cerebrovascular disease (stroke, transient ischemic attack) or dementia, that may increase the subject risk associated with study participation, compromise adherence to study procedures and requirements, confound interpretation of the results, and, in the judgment of the investigator, make the subject inappropriate for enrollment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized single blind
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Meal type A<br>Meal type A: equicaloric meal as meal type B and C with differing constituents | Other: One meal<br>* One meal given to assess impact on ammonia levels serially<br>|
| Active Comparator: Meal type B<br>Meal type B: equicaloric meal as meal type A and C with differing constituents | Other: One meal<br>* One meal given to assess impact on ammonia levels serially<br>|
| Experimental: Meal type C<br>Meal type C: equicaloric meal as meal type B and A with differing constituents | Other: One meal<br>* One meal given to assess impact on ammonia levels serially<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Venous ammonia level | Change in these levels hourly from baseline | 3 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Venous ammonia level | Change in these levels from baseline to hour 1 | 1 hour | 
| Venous ammonia level | Change in these levels from baseline to hour 2 | 2 hours | 
| Venous ammonia level | Change in these levels from baseline to hour 3 | 3 hours |