Clinical trial NCT04474743: Malnutrition in Chronic Gastrointestinal Diseases, Cross-sectional Study
Official title: 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))
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Liver Cirrhoses
Chronic Pancreatitis
Short Bowel Syndrome
Lead sponsor: University Medicine Greifswald
Sponsor class: OTHER
Collaborators: name: University Medical Center Rostock
name: University of Applied Sciences Neubrandenburg
name: Leibniz Institute for Farm Animal Biology (FBN)
First posted: 2020-07-17
Enrollment: 345
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients eligible for study participation will be recruited at the University hospitals in the cities of Rostock and Greifswald (Northeast Germany). Hospitalized as well outcare-patients will be considered for recruitment. Healthy controls will be recruited from the general public in the city of Neubrandenburg (Northeast Germany).

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Sarcopenia
timeFrame: Baseline
measure: Quantitative Food Intake
timeFrame: Baseline
measure: Qualitative Food Intake
timeFrame: Baseline
measure: Physical Activity
timeFrame: Baseline
measure: Body Weight
timeFrame: Baseline
measure: Height
timeFrame: Baseline
measure: Body Mass Index
timeFrame: Baseline
measure: Waist Circumference
timeFrame: Baseline
measure: Hip Circumference
timeFrame: Baseline
measure: Waist-to-Hip Ratio
timeFrame: Baseline
measure: Upper Arm Circumference
timeFrame: Baseline
measure: Triceps Skinfold Thickness
timeFrame: Baseline
measure: Fat Free Mass
timeFrame: Baseline
measure: Skeletal Muscle Mass
timeFrame: Baseline
measure: Fat Mass
timeFrame: Baseline
measure: Total Body Water
timeFrame: Baseline
measure: Extracellular Water
timeFrame: Baseline
measure: Phase Angle
timeFrame: Baseline
measure: Muscle Strength
timeFrame: Baseline
measure: Hemoglobin
timeFrame: Baseline
measure: Hematocrit
timeFrame: Baseline
measure: Mean Corpuscular Volume
timeFrame: Baseline
measure: Mean Corpuscular Hemoglobin Concentration
timeFrame: Baseline
measure: Reticulocyte Count
timeFrame: Baseline
measure: Sodium
timeFrame: Baseline
measure: Potassium
timeFrame: Baseline
measure: Calcium
timeFrame: Baseline
measure: Magnesium
timeFrame: Baseline
measure: Phosphate
timeFrame: Baseline
measure: Aspartate Transaminase
timeFrame: Baseline
measure: Alanine Aminotransferase
timeFrame: Baseline
measure: Gamma-glutamyl Transferase
timeFrame: Baseline
measure: Alkaline Phosphatase
timeFrame: Baseline
measure: Bilirubin
timeFrame: Baseline
measure: C-reactive Protein
timeFrame: Baseline
measure: Interleukin-1 Beta
timeFrame: Baseline
measure: Interleukin-6
timeFrame: Baseline
measure: Tumor Necrosis Factor Alpha
timeFrame: Baseline
measure: Albumin
timeFrame: Baseline
measure: Creatinine
timeFrame: Baseline
measure: Urea
timeFrame: Baseline
measure: Uric Acid
timeFrame: Baseline
measure: Glucose
timeFrame: Baseline
measure: Glycated hemoglobin
timeFrame: Baseline
measure: Insulin
timeFrame: Baseline
measure: Total Cholesterol
timeFrame: Baseline
measure: High-density Lipoprotein Cholesterol
timeFrame: Baseline
measure: Low-density Lipoprotein Cholesterol
timeFrame: Baseline
measure: Triglycerides
timeFrame: Baseline
measure: Non-essential Fatty Acids
timeFrame: Baseline
measure: Zinc
timeFrame: Baseline
measure: Iron
timeFrame: Baseline
measure: Plasma Metabolome
timeFrame: Baseline
measure: Intestinal Barrier Function
timeFrame: Baseline
measure: Expression of Intestinal Ion Transporters
timeFrame: Baseline
Secondary outcomes:
measure: Malnutrition-Sarcopenia Score
timeFrame: Baseline
measure: Validity of the Study of Health in Pomerania Food Frequency Questionnaire
timeFrame: Baseline
measure: Factor Analysis of Phenotypes of Sarcopenia and Malnutrition
timeFrame: Baseline
Other outcomes:
Locations:
city: Greifswald
country: Germany
facility: University Medicine Greifswald
city: Neubrandenburg
country: Germany
facility: University of Applied Sciences Neubrandenburg
city: Rostock
country: Germany
facility: Univeristy Medicine Rostock
Study officials:
affiliation: University Medicine Rostock
name: Prof. Dr. med. Lamprecht
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wiese ML, Gartner S, von Essen N, Doller J, Frost F, Tran QT, Weiss FU, Meyer F, Valentini L, Garbe LA, Metges CC, Bannert K, Sautter LF, Ehlers L, Jaster R, Lamprecht G, Steveling A, Lerch MM, Aghdassi AA. Malnutrition Is Highly Prevalent in Patients With Chronic Pancreatitis and Characterized by Loss of Skeletal Muscle Mass but Absence of Impaired Physical Function. Front Nutr. 2022 Jun 1;9:889489. doi: 10.3389/fnut.2022.889489. eCollection 2022.