The BRAINFOOD Trial to Prevent Recurrent Hepatic Encephalopathy.

Study Overview
=================
Brief Summary
-----------------
This study is being completed for patients with cirrhosis, including patients with a prior history of hepatic encephalopathy (HE) to evaluate the feasibility and benefits of medically-tailored meals as an intervention. Patients will be enrolled from the University of Michigan and will complete the baseline assessments in-person or remotely. In addition participants will complete study related materials before, during and after treatment with medically-tailored meals (MTM). After completing the study meals, participants will return for follow-up or have this visit completed remotely as well as have an observational period for 12 more weeks.

Official Title
-----------------
Medically-Tailored Meals to Prevent Recurrent Hepatic Encephalopathy: The BRAINFOOD Pilot Trial

Conditions
-----------------
Cirrhosis, Ascites, Liver Diseases, Frailty, Sarcopenia, Hepatic Encephalopathy

Intervention / Treatment
-----------------
* Other: Medically-tailored meals (MTM)
* Dietary Supplement: Protein supplements
* Behavioral: Nutrition education handout


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of cirrhosis will be based upon: liver biopsy, OR history of cirrhosis complication: ascites, variceal bleeding, hepatic encephalopathy, OR 2 of the following 4 criteria: Ultrasound, Computed tomography (CT), or Magnetic resonance imaging (MRI) findings of cirrhosis (cirrhotic appearing liver, splenomegaly, varices, ascites) Fibroscan liver stiffness score >13 kilopascals (kPa) Laboratory testing: aspartate aminotransferase/platelet ratio index (APRI) >2.0 CT, MRI or esophagogastroduodenoscopy (EGD) showing presence of esophageal varices Patients with history of > grade 2 HE within 180 days of enrollment based on review of clinical documentation verifying the event. If a description of HE symptoms is provided in clinical documentation, but it is unclear if it meets Grade 2 criteria, the principal investigator will assess the clinical documentation and provide an HE grade. Exclusion Criteria: Non-English speaking Model for End-Stage Liver Disease (MELD) Score > 20 Pregnancy (self-reported) Unable or unwilling to provide consent History of liver transplant Current or planned admission to a nursing facility Serum creatinine > 2.0 milligrams per deciliter (mg/dL) (with the exception that we will include patients with a serum creatinine > 2.0 mg/dL if they are receiving hemodialysis) Disorientation at the time of enrollment Barcelona-Clinic Liver Cancer (BCLC) Stage D Hepatocellular Carcinoma with Child-Turcotte-Pugh (CTP) Class C History of eating disorder

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Medically-tailored meals<br>Participants will receive meals that adhere to their specified nutritional targets dependent upon their cirrhosis complication of hepatic encephalopathy (HE) and/or ascites. Participants with HE will receive high-protein (approximately 1 gram of medication per kilogram of the body weight (1g/kg/day) and high-calorie (approximately 30c/kg/day) meals. Participants with HE and ascites will receive high-protein and high-calorie meals that are also low-sodium (less than 2000 grams a day). | Other: Medically-tailored meals (MTM)<br>* After the run-in baseline period participants will be expected to consume the meals and protein supplements meals between approximately Weeks 4 - 11 of the study. Additionally, participants will complete surveys before, during and after the meals.<br>Dietary Supplement: Protein supplements<br>* A daytime and nighttime protein supplement will be provided after the baseline visit and should be consumed daily at home during the same study days as MTM. The daytime protein supplement is a protein bar (ZonePerfect or Perfect Bar). The nighttime supplement is a protein powder or liquid that can be dissolved in either water or milk. This is provided to participants with ProCel Vanilla Whey Protein powder which provides 15 grams of protein per serving or the ProCel LiquaCel liquid protein supplement mango, grape, watermelon and/or lemon flavors which provides 16g of protein per serving.<br>Behavioral: Nutrition education handout<br>* A standardized nutrition education handout containing instructions on following a high-protein and sodium restricted diet (depending on the presence of ascites) will be given as part of Standard of Care.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall subject retention rate based on proportion of subjects who complete all study visits | Overall subject retention rate based on proportion of subjects who complete all study visits | up to 27 weeks post enrollment | 
| Subject adherence rate to Medically-Tailored Meals (MTM) based on proportion of subjects who consume ≥75% of delivered meals and evening snack | The subject adherence rate to Medically-Tailored Meals (MTM) based on proportion of subjects who consume ≥75% of delivered meals and evening snack | up to 11 weeks post enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects who complete all study assessments and procedures | The number of subjects who complete all study assessments and procedures compared to the number of subjects who do not complete all study assessments and procedures | up to 27 weeks post enrollment | 
| Number of eligible candidates screened and percentage of those enrolled | The number of eligible candidates screened and the percentage of eligible candidates who enrolled in the study | approximately 1 year (enrollment period) | 
| The proportion of subjects who complete all 24-hour Diet Recall interviews | The number of subjects who complete all 24-hour Diet Recall interviews compared to the number of subjects who do not complete all 24-Hour Diet Recall interviews | up to 11 weeks post enrollment | 
| Change in one minute Animal Naming Test (ANT) | The participants list as many unique animals as possible in 60 seconds. | baseline, up to 27 weeks | 
| Change is EncephalApp - Stroop score | This is a computerized, timed test of attention conducted on an Interactive Personal Application Device (iPad) or smart device by a phone application that asks patients to identify the color of words. The score is the sum of the time it takes to complete color-word concordance and color-word discordance. A score of less than 190 is considered 'normal' cognitive function. Subjects who are color-blind will be excluded from performing this test. | baseline, up to 13 weeks | 
| The percentage of enrolled subjects that drop out of study | The percentage of enrolled subjects who drop-out of either study stage before the final study visit due to withdrawal by subject or lost to follow-up, and not due to death, withdrawal by study staff or principal investigator discretion. | up to 27 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Nutrition