Malnutrition in Chronic Gastrointestinal Diseases, Cross-sectional Study

Study Overview
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Brief Summary
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Malnutrition and muscle wasting are common consequences of life-threatening, chronic diseases of the gastrointestinal tract. Such diseases include liver cirrhosis, chronic pancreatitis and short bowel syndrome. Malnutrition and muscle wasting increase the risk of complications, reduce the life expectancy and impair the quality of life. The development of malnutrition and muscle wasting is different, as is the diagnosis and nutritional treatment. There are also different mechanisms of origin for the underlying diseases. The aim of the study is to compare data related to nutrition and physical condition of patients with liver cirrhosis, chronic pancreatitis and short bowel syndrome. Malnutrition and muscle wasting within the specific diseases will be characterized and possible correlations will be identified. For this, malnourished and non-malnourished patients of the different diseases are compared with controls patients with non-specific complaints of the gastrointestinal tract as well as with healthy study participants. Data on food intake, physical activity, body composition and body measurements as well as muscle strength and muscle function are recorded. Blood values as well as transport and barrier properties of the intestine will also be examined.

Detailed Description
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Malnutrition and sarcopenia are consequences of life-threatening gastroenterological diseases such as liver cirrhosis, chronic pancreatitis and short bowel syndrome and are associated with a poorer clinical outcome and a reduced quality of life. The diagnostic criteria of both conditions differ, as do the consequences for adequate nutritional therapy. Nevertheless, malnutrition and sarcopenia are often discussed in confusion in the literature. In addition, the underlying mechanisms of malnutrition and sarcopenia can differ in the various diseases. The aim of the study is to compare nutrition-associated parameters from patients with liver cirrhosis, chronic pancreatitis and short bowel syndrome, to characterize the disease-specific phenotype of malnutrition and sarcopenia of the examined diseases and to obtain information on mechanistic relationships. The pathophysiological understanding of the clinical settings as well as the development of malnutrition and sarcopenia is important for choosing specific nutritional therapies. For this, malnourished and non-malnourished patients of each examined disease are compared with controls from patients with non-specific, abdominal symptoms and healthy control subjects. Data on food intake, physical activity, body composition and anthropometry as well as muscle strength and muscle function are recorded. Clinical and chemical blood parameters, the plasma metabolome as well as transport and barrier proteins of the intestine are also examined.

Official Title
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Multi-center, Controlled Cross-sectional Analysis of the Phenotype of Malnutrition in Patients With Liver Cirrhosis, Chronic Pancreatitis and Short Bowel Syndrome (as Part of the Joint Project Enteral Nutrition in Malnutrition Due to Diseases of the Gastrointestinal Tract: From Basic Understanding to an Innovative Treatment Concept (EnErGie))

Conditions
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Liver Cirrhoses, Chronic Pancreatitis, Short Bowel Syndrome

Intervention / Treatment
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* Other: No intervention - cross-sectional observational only


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Liver Cirrhosis: based on clinical and imaging criteria (sonography or computed tomography (CT) or magnetic resonance imaging (MRI)) without evidence of hepatocellular carcinoma Child-Pugh Stadium A-C Chronic Pancreatitis: based on imaging criteria (endoscopic ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance cholangiopancreatography (MRCP)) large and small duct disease with or without exocrine insufficiency with or without endocrine insufficiency patients after left pancreatic resection or pancreaticojejunostomy or duodenal pancreatic head resection Short Bowel Syndrome (SBS): - based on clinical anamnestic criteria and state after bowel resection followed by primary or secondary oral autonomy (intestinal failure) Control Patients: patients without known underlying gastroenterological disease with an indication for esophago-gastro-duodenoscopy for symptom clarification negative Nutritional Risk Screening (NRS-2002 < 3) gastroscopy without clinically relevant result (mild gastritis aspect, small axial hernia, typical glandular cysts, typical brunneromas can be included) Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Exclusion Criteria: General Exclusion Criteria: parenteral nutrition in the previous 6 months pacemaker or implanted defibrillator pregnancy or lactation lack of ability to answer the questionnaires taking certain medications during the previous 4 weeks (protein pump inhibitors and H2 antagonists, except medication on demand or ≤ 4 weeks continuously, antibiotics, narcotics, non-opioid analgesics except medication on demand (≤ 1 day/week), anticholinergics, antidepressants, motility drugs (metoclopramide, motilium, bromocriptine, prucalopride), thyroid drugs except stable thyroid hormone substitution with euthyroid metabolism, steroids, immunomodulators, anti-inflammatory biologics) Subsequent Exclusion of Control Patients: if, contrary to expectations, malnutrition is diagnosed in spite of an inconspicuous NRS-2002 within the framework of the study as well as in the case of relevant, conspicuous esophago-gastro-duodenoscopy findings Specific Exclusion Criteria: Liver Cirrhosis: steatohepatitis according to clinical or laboratory parameters acute alcoholic hepatitis according to clinical and imaging parameters (sonography, CT, MRI) existing transjugular intrahepatic portosystemic shunt (TIPS) known hepatocellular carcinoma (HCC) state after liver transplantation Chronic Pancreatitis: acute pancreatitis extrapancreatic infection coexisting liver cirrhosis based on clinical and imaging parameters state after surgery with alteration of food flow (partial or total pancreaticoduodenectomy) known pancreatic carcinoma or state after therapy of pancreatic carcinoma (surgery or chemotherapy or radiation) Short Bowel Syndrome (SBS): acute phase of intestinal insufficiency (less than 28 days after resection) intravenous substitution of macronutrients (water, electrolytes, glucose, amino acids or lipids (intestinal insufficiency) intramuscular substitution of micronutrients is allowed (e.g. vitamin B12) uncontrolled underlying disease leading to SBS (e.g. active Crohn's disease) Control Patients: major underlying and concomitant diseases food allergies Healthy controls: tumor diseases in the past 5 years medically diagnosed, serious chronic diseases or changes in the gastrointestinal tract that may affect the absorption of nutrients (e.g. celiac disease, chronic inflammatory bowel disease or irritable bowel syndrome diagnosed according to Rome IV criteria, relevant bowel resections including short bowel syndrome) rheumatic diseases requiring permanent drug therapy (rheumatoid arthritis, fibromyalgia) chronic use of anti-inflammatory or pain-relieving drugs or use of anti-inflammatory or pain-relieving drugs for more than 3 days in the last 3 weeks average daily alcohol consumption > 20 g in women and > 30 g in men diagnosed severe liver disease requiring medical attention and drug therapy (liver cirrhosis, non-alcoholic steatohepatitis (NASH) / alcoholic steatohepatitis (ASH), hepatitides) acute or chronic pancreatitis acute and chronic renal failure myocardial infarction or cerebral insult within 6 months prior to examination coronary artery disease/pAVK (peripheral artery disease (PAD)) heart failure with stages 3 and 4 according to NYHA (New York Heart Association) classification severe chronic pulmonary disease (COPD) history of significant neurological or psychiatric diseases (including epilepsy, bipolar disorders, dementia and neuromuscular diseases) presence of pareses including mono- and diparesis rare congenital metabolic diseases (cystic fibrosis, phenylketonuria) expected altered body composition (extreme sports activity < 2h/day), edema, amputation of the extremities (arm and/or leg) highly atypical or restrictive dietary choices/concepts followed voluntarily (macrobiotics, paleo-diet, Atkins diet, Mayo diet, instinctive diets) or due to food intolerances/allergies simultaneous participation in other studies associated with drug use and potentially having a significant impact on body composition or dietary behaviour

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Liver Cirrhosis<br>Patients diagnosed with liver cirrhosis. | Other: No intervention - cross-sectional observational only<br>* No intervention - cross-sectional observational only<br>|
| Chronic Pancreatitis<br>Patients diagnosed with chronic pancreatitis. | Other: No intervention - cross-sectional observational only<br>* No intervention - cross-sectional observational only<br>|
| Short Bowel Syndrome<br>Patients diagnosed with short bowel Syndrome. | Other: No intervention - cross-sectional observational only<br>* No intervention - cross-sectional observational only<br>|
| Control Patients<br>Otherwise healthy patients visiting hospital with other non-severe diseases. | Other: No intervention - cross-sectional observational only<br>* No intervention - cross-sectional observational only<br>|
| Healthy Controls<br>Healthy subjects recruited from the general population. | Other: No intervention - cross-sectional observational only<br>* No intervention - cross-sectional observational only<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sarcopenia | Descriptive and inferential determination of the prevalence of sarcopenia according to the European Working Group on Sarcopenia in Older People 2 criteria (EWGSOP2 criteria) in malnourished and non malnourished patients with liver cirrhosis, chronic pancreatitis or short bowel syndrome - as a total group and separated by type of disease | Baseline | 
| Quantitative Food Intake | Determination of quantitative food intake assessed by the German Health Interview and Examination Survey for Adults Food Frequency Questionnaire (DEGS-FFQ) in comparison with non malnourished and non-sarcopenia patients and in comparison with healthy control subjects | Baseline | 
| Qualitative Food Intake | Determination of qualitative food intake assessed by the Study of Health in Pomerania Food Frequency Questionnaire (SHIP-FFQ) in comparison with non malnourished and non-sarcopenia patients and in comparison with healthy control subjects | Baseline | 
| Physical Activity | Determination of physical activity assessed by the International Physical Activity Questionnaire (IPAQ) Short Form in comparison with non malnourished and non-sarcopenia patients and in comparison with healthy control subjects | Baseline | 
| Body Weight | Determination of body weight measured in kilograms in comparison with non malnourished and non-sarcopenia patients and in comparison with healthy control subjects | Baseline | 
| Height | Determination of height measured in meters in comparison with non malnourished and non-sarcopenia patients and in comparison with healthy control subjects | Baseline | 
| Body Mass Index | Determination of body mass index in kg/m^2 (calculated from the values obtained for body weight and height) in comparison with non malnourished and non-sarcopenia patients and in comparison with healthy control subjects | Baseline | 
| Waist Circumference | Determination of waist circumference measured in centimeters in comparison with non malnourished and non-sarcopenia patients and in comparison with healthy control subjects | Baseline | 
| Hip Circumference | Determination of hip circumference measured in centimeters in comparison with non malnourished and non-sarcopenia patients and in comparison with healthy control subjects | Baseline | 
| Waist-to-Hip Ratio | Determination of waist-to-hip ratio (calculated from the values obtained for waist and hip circumference) in comparison with non malnourished and non-sarcopenia patients and in comparison with healthy control subjects | Baseline | 
| Upper Arm Circumference | Determination of upper arm circumference measured in centimeters in comparison with non malnourished and non-sarcopenia patients and in comparison with healthy control subjects | Baseline | 
| Triceps Skinfold Thickness | Determination of triceps skinfold thickness measured in millimeters in comparison with non malnourished and non-sarcopenia patients and in comparison with healthy control subjects | Baseline | 
| Fat Free Mass | Determination of fat free mass measured by Bioelectrical Impedance Analysis (BIA) in comparison with non malnourished and non-sarcopenia patients and in comparison with healthy control subjects | Baseline | 
| Skeletal Muscle Mass | Determination of skeletal muscle mass measured by Bioelectrical Impedance Analysis (BIA) in comparison with non malnourished and non-sarcopenia patients and in comparison with healthy control subjects | Baseline | 
| Fat Mass | Determination of fat mass measured by Bioelectrical Impedance Analysis (BIA) in comparison with non malnourished and non-sarcopenia patients and in comparison with healthy control subjects | Baseline | 
| Total Body Water | Determination of total body water measured by Bioelectrical Impedance Analysis (BIA) in comparison with non malnourished and non-sarcopenia patients and in comparison with healthy control subjects | Baseline | 
| Extracellular Water | Determination of extracellular water measured by Bioelectrical Impedance Analysis (BIA) in comparison with non malnourished and non-sarcopenia patients and in comparison with healthy control subjects | Baseline | 
| Phase Angle | Determination of phase angle measured by Bioelectrical Impedance Analysis (BIA) in comparison with non malnourished and non-sarcopenia patients and in comparison with healthy control subjects | Baseline | 
| Muscle Strength | Determination of muscle strength measured by a handgrip strength dynamometer in comparison with non malnourished and non-sarcopenia patients and in comparison with healthy control subjects | Baseline | 
| Hemoglobin | Determination of hemoglobin level in comparison to control patients and in comparison to healthy control subjects | Baseline | 
| Hematocrit | Determination of hematocrit level in comparison to control patients and in comparison to healthy control subjects | Baseline | 
| Mean Corpuscular Volume | Determination of mean corpuscular volume in comparison to control patients and in comparison to healthy control subjects | Baseline | 
| Mean Corpuscular Hemoglobin Concentration | Determination of mean corpuscular hemoglobin concentration in comparison to control patients and in comparison to healthy control subjects | Baseline | 
| Reticulocyte Count | Determination of reticulocyte count in comparison to control patients and in comparison to healthy control subjects | Baseline | 
| Sodium | Determination of plasma concentration of sodium in comparison to control patients and in comparison to healthy control subjects | Baseline | 
| Potassium | Determination of plasma concentration of potassium in comparison to control patients and in comparison to healthy control subjects | Baseline | 
| Calcium | Determination of plasma concentration of calcium in comparison to control patients and in comparison to healthy control subjects | Baseline | 
| Magnesium | Determination of plasma concentration of magnesium in comparison to control patients and in comparison to healthy control subjects | Baseline | 
| Phosphate | Determination of plasma concentration of phosphate in comparison to control patients and in comparison to healthy control subjects | Baseline | 
| Aspartate Transaminase | Determination of plasma concentration of aspartate transferase in comparison to control patients and in comparison to healthy control subjects | Baseline | 
| Alanine Aminotransferase | Determination of plasma concentration of alanine aminotransferase in comparison to control patients and in comparison to healthy control subjects | Baseline | 
| Gamma-glutamyl Transferase | Determination of plasma concentration of gamma-glutamyl transferase in comparison to control patients and in comparison to healthy control subjects | Baseline | 
| Alkaline Phosphatase | Determination of plasma concentration of alkaline phosphatase in comparison to control patients and in comparison to healthy control subjects | Baseline | 
| Bilirubin | Determination of plasma concentration of bilirubin in comparison to control patients and in comparison to healthy control subjects | Baseline | 
| C-reactive Protein | Determination of plasma concentration of C-reactive protein in comparison to control patients and in comparison to healthy control subjects | Baseline | 
| Interleukin-1 Beta | Determination of serum concentration of interleukin-1 beta in comparison to control patients and in comparison to healthy control subjects | Baseline | 
| Interleukin-6 | Determination of plasma concentration of interleukin-6 in comparison to control patients and in comparison to healthy control subjects | Baseline | 
| Tumor Necrosis Factor Alpha | Determination of serum concentration of tumor necrosis factor alpha in comparison to control patients and in comparison to healthy control subjects | Baseline | 
| Albumin | Determination of plasma concentration of albumin in comparison to control patients and in comparison to healthy control subjects | Baseline | 
| Creatinine | Determination of plasma concentration of creatinine in comparison to control patients and in comparison to healthy control subjects | Baseline | 
| Urea | Determination of plasma concentration of urea in comparison to control patients and in comparison to healthy control subjects | Baseline | 
| Uric Acid | Determination of plasma concentration of uric acid in comparison to control patients and in comparison to healthy control subjects | Baseline | 
| Glucose | Determination of plasma concentration of glucose in comparison to control patients and in comparison to healthy control subjects | Baseline | 
| Glycated hemoglobin | Determination of plasma concentration of glycated hemoglobin in comparison to control patients and in comparison to healthy control subjects | Baseline | 
| Insulin | Determination of plasma concentration of insulin in comparison to control patients and in comparison to healthy control subjects | Baseline | 
| Total Cholesterol | Determination of plasma concentration of total cholesterol in comparison to control patients and in comparison to healthy control subjects | Baseline | 
| High-density Lipoprotein Cholesterol | Determination of plasma concentration of high-density lipoprotein cholesterol in comparison to control patients and in comparison to healthy control subjects | Baseline | 
| Low-density Lipoprotein Cholesterol | Determination of plasma concentration of low-density lipoprotein cholesterol in comparison to control patients and in comparison to healthy control subjects | Baseline | 
| Triglycerides | Determination of plasma concentration of triglycerides in comparison to control patients and in comparison to healthy control subjects | Baseline | 
| Non-essential Fatty Acids | Determination of plasma concentration of non-essential fatty acids in comparison to control patients and in comparison to healthy control subjects | Baseline | 
| Zinc | Determination of serum concentration of zinc in comparison to control patients and in comparison to healthy control subjects | Baseline | 
| Iron | Determination of plasma concentration of iron in comparison to control patients and in comparison to healthy control subjects | Baseline | 
| Plasma Metabolome | In a participants subgroup, investigations of the plasma metabolome in comparison with control patients and in comparison with healthy control subjects | Baseline | 
| Intestinal Barrier Function | Determination of the intestinal barrier function in a patient subgroup in comparison to control patients (using proximal small intestinal biopsies, qRT-PCR (Real Time Polymerase Chain Reaction) of different intestinal barrier markers) | Baseline | 
| Expression of Intestinal Ion Transporters | Determination of the expression of intestinal ion transporters in a patient subgroup in comparison to control patients (using proximal small intestinal biopsies, qRT-PCR (Real Time Polymerase Chain Reaction) of different intestinal transport markers) | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Malnutrition-Sarcopenia Score | Correlative, factorial or other presentation of the results including statistical-mathematical argumentation of the usefulness of a combined malnutrition-sarcopenia score (MaSa score) for practical application. | Baseline | 
| Validity of the Study of Health in Pomerania Food Frequency Questionnaire | Determination of the validity of the Study of Health in Pomerania Food Frequency Questionnaire (SHIP-FFQ) by assessment of percent agreement with the German Health Interview and Examination Survey for Adults Food Frequency Questionnaire (DEGS-FFQ) | Baseline | 
| Factor Analysis of Phenotypes of Sarcopenia and Malnutrition | Determination of parameters characterizing phenotypes of sarcopenia and malnutrition in the investigated gastroenterological disease (liver cirrhosis, chronic pancreatitis, short bowel syndrome) by factor analysis | Baseline |