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

Primary Purpose

NASH - Nonalcoholic Steatohepatitis

Status
Completed
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
oatmeal flakes with prebiotic food supplements
millet flakes
Sponsored by
RWTH Aachen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for NASH - Nonalcoholic Steatohepatitis focused on measuring Liver health, Diet, Microbiom

Eligibility Criteria

undefined - 75 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Medical University of Vienna
  • University Hospital RWTH Aachen
  • Sahlgrenska University Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Experimental

Experimental

Arm Label

Group 1

Group 2

Group 3

Arm Description

Patients consuming placebo (millet flakes) each day

Patients consuming oatmeal flakes with a low dosage of prebiotic food supplements

Patients consuming oatmeal flakes with a high dosage of prebiotic food supplements

Outcomes

Primary Outcome Measures

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.
CAP measurement (dB/m)
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.
Determination of ALT concentration (U/l) in blood samples

Secondary Outcome Measures

Influence of dietary supplement in oat bran on concentration of AST
Determination of AST concentration (U/l) in blood samples
Influence of dietary supplement in oat bran on the concentration of gamma-GT
Determination of gamma-GT concentration (U/l) in blood samples
Influence of dietary supplement in oat bran on liver steatosis
Sonography - Performing an abdominal ultrasound examination to detect liver steatosis
Influence of dietary supplement in oat bran on bile acid metabolism
Determination of bile acid composition in stool samples
Influence of dietary supplement in oat bran on the composition of the intestinal microbiome
Determination of microbiom in stool samples (bacterial DNA and RNA are isolated from the stool to determine the microbial composition)
Influence of dietary supplement in oat bran on intestinal permeability marker like citrullin
Determination of intestinal permeability marker like citrullin (µmol/l)
Influence of dietary supplement in oat bran on metabolic markers
Determination of concentration of diffenrent, previously not defined metabolic markers in blood samples by untargeted metabolomics analysis
Influence of dietary supplement in oat bran on inflammatory markers of NASH
Determination of concentration of previously not defined inflammatory markers of NASH in blood samples by multiplex assays
Influence of dietary supplement in oat bran on blood pressure
Measurement of blood pressure (mmHg)
Assessment of quality of life
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)
Assessment of the feeling of satiety/gastrointestinal symptoms
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"

Full Information

First Posted
March 14, 2019
Last Updated
August 15, 2023
Sponsor
RWTH Aachen University
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1. Study Identification

Unique Protocol Identification Number
NCT03897218
Brief Title
Dietary Modulation of Intestinal Microbiota as Trigger of Liver Health: Role of Bile Acids - "A Diet for Liver Health"
Acronym
ADLH
Official Title
Dietary Modulation of Intestinal Microbiota as Trigger of Liver Health: Role of Bile Acids - "A Diet for Liver Health (ADLH)"
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
May 20, 2019 (Actual)
Primary Completion Date
April 30, 2022 (Actual)
Study Completion Date
April 30, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
RWTH Aachen University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
NASH - Nonalcoholic Steatohepatitis
Keywords
Liver health, Diet, Microbiom

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
84 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1
Arm Type
Placebo Comparator
Arm Description
Patients consuming placebo (millet flakes) each day
Arm Title
Group 2
Arm Type
Experimental
Arm Description
Patients consuming oatmeal flakes with a low dosage of prebiotic food supplements
Arm Title
Group 3
Arm Type
Experimental
Arm Description
Patients consuming oatmeal flakes with a high dosage of prebiotic food supplements
Intervention Type
Dietary Supplement
Intervention Name(s)
oatmeal flakes with prebiotic food supplements
Intervention Description
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.
Intervention Type
Dietary Supplement
Intervention Name(s)
millet flakes
Intervention Description
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 Measure Information:
Title
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.
Description
CAP measurement (dB/m)
Time Frame
20 weeks
Title
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.
Description
Determination of ALT concentration (U/l) in blood samples
Time Frame
20 weeks
Secondary Outcome Measure Information:
Title
Influence of dietary supplement in oat bran on concentration of AST
Description
Determination of AST concentration (U/l) in blood samples
Time Frame
20 weeks
Title
Influence of dietary supplement in oat bran on the concentration of gamma-GT
Description
Determination of gamma-GT concentration (U/l) in blood samples
Time Frame
20 weeks
Title
Influence of dietary supplement in oat bran on liver steatosis
Description
Sonography - Performing an abdominal ultrasound examination to detect liver steatosis
Time Frame
20 weeks
Title
Influence of dietary supplement in oat bran on bile acid metabolism
Description
Determination of bile acid composition in stool samples
Time Frame
20 weeks
Title
Influence of dietary supplement in oat bran on the composition of the intestinal microbiome
Description
Determination of microbiom in stool samples (bacterial DNA and RNA are isolated from the stool to determine the microbial composition)
Time Frame
20 weeks
Title
Influence of dietary supplement in oat bran on intestinal permeability marker like citrullin
Description
Determination of intestinal permeability marker like citrullin (µmol/l)
Time Frame
20 weeks
Title
Influence of dietary supplement in oat bran on metabolic markers
Description
Determination of concentration of diffenrent, previously not defined metabolic markers in blood samples by untargeted metabolomics analysis
Time Frame
20 weeks
Title
Influence of dietary supplement in oat bran on inflammatory markers of NASH
Description
Determination of concentration of previously not defined inflammatory markers of NASH in blood samples by multiplex assays
Time Frame
20 weeks
Title
Influence of dietary supplement in oat bran on blood pressure
Description
Measurement of blood pressure (mmHg)
Time Frame
20 weeks
Title
Assessment of quality of life
Description
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)
Time Frame
20 weeks
Title
Assessment of the feeling of satiety/gastrointestinal symptoms
Description
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"
Time Frame
20 weeks

10. Eligibility

Sex
All
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christian Trautwein, Prof. Dr.
Organizational Affiliation
Uniklinik RWTH Aachen, Med. Klinik III
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medical University of Vienna
City
Vienna
Country
Austria
Facility Name
University Hospital RWTH Aachen
City
Aachen
Country
Germany
Facility Name
Sahlgrenska University Hospital
City
Gothenburg
Country
Sweden

12. IPD Sharing Statement

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

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