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Dietary Modulation of Intestinal Microbiota as Trigger of Liver Health: Role of Bile Acids - "A Diet for Liver Health" (ADLH)

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ClinicalTrials.gov Identifier: NCT03897218
Recruitment Status : Recruiting
First Posted : April 1, 2019
Last Update Posted : May 22, 2019
Sponsor:
Information provided by (Responsible Party):
RWTH Aachen University

Brief Summary:
Studies in recent years have demonstrated that the commensal intestinal flora (microbiome) plays a key role in the development of nonalcoholic steatohepatitis (NASH). An unfavourable microbiom can trigger disease development and progression. On the other hand, recent data show that modulation of the microbiom by a diet can prevent the developement of a NASH. Mechanisms of interaction between nutrition, microbiome, intestine and liver are largely unknown. In this research project, the effect of a fibre-rich oat bran on NASH will therefore be investigated. A better understanding of the interaction between diet, microbiome, intestine and liver could form the basis for new preventive therapies of NASH.

Condition or disease Intervention/treatment Phase
NASH - Nonalcoholic Steatohepatitis Dietary Supplement: oatmeal flakes with prebiotic food supplements Dietary Supplement: millet flakes Not Applicable

Detailed Description:

In recent years, the results of animal experiments and some human intervention studies indicate that the commensal intestinal flora (microbiome) plays a key role in the development of nonalcoholic steatohepatitis (NASH). An unfavourable composition of the microbiome can trigger disease development and progression. On the other hand, recent data show that modulation of the microbiome through diet, such as a high-fibre diet, can prevent the developement of a NASH. It has been shown that the uptake of fibre-rich oats reduces LDL and total cholesterol without altering the HDL cholesterol level. Indeed, the results of several human intervention studies suggest that a regular intake of oat flakes with prebiotic food supplements is sufficient to lower LDL and total cholesterol levels. In a small clinical trial it was also shown that an intake of oat bran with prebiotic food supplements in two servings per day was associated with a significant reduction in ALT and AST activity in the serum of overweight individuals with signs of altered liver function. In addition, the use of oat bran to influence postprandial glucose and insulin response and satiety was discussed.

However, the mechanisms underlying the positive effects of treatments with pro-, pre- or synbiotics are not yet fully understood and generally accepted therapeutic strategies are still lacking. The exact influence of a fibre-rich diet on intestinal microbiom and bile acid composition is not yet known. In the research project described, the effect of oat bran with prebiotic food supplements on NASH will be investigated and mechanisms of interaction between diet, microbiome, bile acids and liver will be uncovered. A better understanding of this interaction could form the basis for new preventive therapies of NASH.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 84 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: Dietary Modulation of Intestinal Microbiota as Trigger of Liver Health: Role of Bile Acids - "A Diet for Liver Health (ADLH)"
Actual Study Start Date : May 20, 2019
Estimated Primary Completion Date : October 1, 2020
Estimated Study Completion Date : April 1, 2021


Arm Intervention/treatment
Placebo Comparator: Group 1
Patients consuming placebo (millet flakes) each day
Dietary Supplement: millet flakes
The study participants should consume the prescribed amount of the study product every day. The intake should be divided into 1-2 meals. It is not necessary to limit or change normal eating habits.

Experimental: Group 2
Patients consuming oatmeal flakes with a low dosage of prebiotic food supplements
Dietary Supplement: oatmeal flakes with prebiotic food supplements
The study participants should consume the prescribed amount of the study product every day. The intake should be divided into 1-2 meals. It is not necessary to limit or change normal eating habits.

Experimental: Group 3
Patients consuming oatmeal flakes with a high dosage of prebiotic food supplements
Dietary Supplement: oatmeal flakes with prebiotic food supplements
The study participants should consume the prescribed amount of the study product every day. The intake should be divided into 1-2 meals. It is not necessary to limit or change normal eating habits.




Primary Outcome Measures :
  1. Evaluation of the influence of a dietary supplement in oat bran on the course of disease in the early stages of NASH by CAP (Controlled Attenuation Parameter) measurement to determine liver steatosis. [ Time Frame: 20 weeks ]
    CAP measurement (dB/m)

  2. Evaluation of the influence of a dietary supplement in oat bran on the course of disease in the early stages of NASH by determination ALT-concentration in blood samples. [ Time Frame: 20 weeks ]
    Determination of ALT concentration (U/l) in blood samples


Secondary Outcome Measures :
  1. Influence of dietary supplement in oat bran on concentration of AST [ Time Frame: 20 weeks ]
    Determination of AST concentration (U/l) in blood samples

  2. Influence of dietary supplement in oat bran on the concentration of gamma-GT [ Time Frame: 20 weeks ]
    Determination of gamma-GT concentration (U/l) in blood samples

  3. Influence of dietary supplement in oat bran on liver steatosis [ Time Frame: 20 weeks ]
    Sonography - Performing an abdominal ultrasound examination to detect liver steatosis

  4. Influence of dietary supplement in oat bran on bile acid metabolism [ Time Frame: 20 weeks ]
    Determination of bile acid composition in stool samples

  5. Influence of dietary supplement in oat bran on the composition of the intestinal microbiome [ Time Frame: 20 weeks ]
    Determination of microbiom in stool samples (bacterial DNA and RNA are isolated from the stool to determine the microbial composition)

  6. Influence of dietary supplement in oat bran on intestinal permeability marker like citrullin [ Time Frame: 20 weeks ]
    Determination of intestinal permeability marker like citrullin (µmol/l)

  7. Influence of dietary supplement in oat bran on metabolic markers [ Time Frame: 20 weeks ]
    Determination of concentration of diffenrent, previously not defined metabolic markers in blood samples by untargeted metabolomics analysis

  8. Influence of dietary supplement in oat bran on inflammatory markers of NASH [ Time Frame: 20 weeks ]
    Determination of concentration of previously not defined inflammatory markers of NASH in blood samples by multiplex assays

  9. Influence of dietary supplement in oat bran on blood pressure [ Time Frame: 20 weeks ]
    Measurement of blood pressure (mmHg)

  10. Assessment of quality of life [ Time Frame: 20 weeks ]
    Questionnaires to evaluate quality of life: EQ-5D-5L EQ-5D questionnaires with 5-point Likert scale: "having no problems", "having slight problems", "having moderate problems", "having severe problems" & "being unable to do/having extreme problems" (the answers euquals 1-5 points, with 5 points beeing the worst outcome)

  11. Assessment of the feeling of satiety/gastrointestinal symptoms [ Time Frame: 20 weeks ]

    Questionnaire "Structured Assessment of Gastrointestinal Symptoms" (SAGIS):

    5-point Likert scale from no problem, mild, moderate, severe and very severe problem (0-4 points; 4 points equals "very severe problem"




Information from the National Library of Medicine

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Ages Eligible for Study:   up to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Fatty liver disease diagnosed by sonography (steatosis hepatis grade II and III) and CAP measurement (> 280dB)
  • compliance

Exclusion Criteria:

  • Allergy to oats
  • Alcohol intake of more than 30 g/d (men) or 20 g/d (women)
  • Treatment with ursodeoxycholic acid (UDCA), vitamin E or other NASH drugs 3 months prior to randomization
  • Hepatocellular carcinoma or non-hepatic malignancy within the last 5 years
  • Evidence of cirrhosis of the liver (Child A, B, C) or a history of decompensation
  • Liver diseases not related to NASH, including chronic viral hepatitis B/D or C, autoimmune hepatitis, Wilson's disease or clinically manifest iron overload (heterozygous HFE is permitted), cholestatic liver disease (PBC/PSC)
  • Adiposity surgery in the last 5 years
  • BMI <18.5 kg / m2
  • Liver transplantation
  • Fibroscan> 12 kPa (patients with liver cirrhosis)
  • Lack of CAP and ultrasound evaluation
  • Age > 75 years
  • HIV infection
  • Heart Failure (New York Heart Association Class III - IV)
  • Myocardial infarction, unstable coronary artery disease, coronary artery intervention or stroke in the last 6 months
  • Unstable COPD, chronic inflammatory bowel disease or rheumatoid arthritis
  • Unstable renal failure (changes in serum creatinine > 50% in the last 3 months) or terminal renal failure requiring dialysis
  • Uncontrolled hypertension (SBP / DBP> 180/90 despite therapy)
  • Uncontrolled metabolic conditions (poorly controlled or decompensated diabetes mellitus, HbA1c >7.5%)
  • Food allergies or intolerances that require strict adherence to a diet, such as lactose intolerance or celiac disease.
  • Pregnancy or breastfeeding women (anamnesis)
  • Treatment with drugs or substances that can induce secondary NASH (e.g., tamoxifen, corticosteroids, amiodarone, methotrexate) or alleviate NASH (TNF antagonists) (e.g. metformin)
  • Use of herbal food supplements
  • Any participant who has taken antibiotics 6 weeks prior to the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03897218


Contacts
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Contact: Kai Markus Schneider, Dr. +49 241 80 37727 kmschneider@ukaachen.de

Locations
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Austria
Medical University of Vienna Not yet recruiting
Vienna, Austria
Contact: Michael Trauner, Prof. Dr.         
Germany
University Hospital RWTH Aachen Recruiting
Aachen, Germany
Contact: Christian Trautwein, Prof. Dr.         
Sweden
Sahlgrenska University Hospital Not yet recruiting
Gothenburg, Sweden
Contact: Hanns-Ulrich Marschal, Prof. Dr.         
Sponsors and Collaborators
RWTH Aachen University
Investigators
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Principal Investigator: Christian Trautwein, Prof. Dr. Uniklinik RWTH Aachen, Med. Klinik III

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Responsible Party: RWTH Aachen University
ClinicalTrials.gov Identifier: NCT03897218     History of Changes
Other Study ID Numbers: 17-105
First Posted: April 1, 2019    Key Record Dates
Last Update Posted: May 22, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by RWTH Aachen University:
Liver health
Diet
Microbiom
Additional relevant MeSH terms:
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Fatty Liver
Non-alcoholic Fatty Liver Disease
Liver Diseases
Digestive System Diseases
Bile Acids and Salts
Gastrointestinal Agents