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

NCT ID: NCT03897218

Last Updated: 2023-08-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-20
• Study Completion Date: 2022-04-30

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.

Conditions

NASH - Nonalcoholic Steatohepatitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Group 1

Patients consuming placebo (millet flakes) each day

Group Type: PLACEBO_COMPARATOR

millet flakes

Intervention Type: DIETARY_SUPPLEMENT

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.

Group 2

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

Group Type: EXPERIMENTAL

oatmeal flakes with prebiotic food supplements

Intervention Type: DIETARY_SUPPLEMENT

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.

Group 3

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

Group Type: EXPERIMENTAL

oatmeal flakes with prebiotic food supplements

Intervention Type: DIETARY_SUPPLEMENT

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DIETARY_SUPPLEMENT

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

• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

RWTH Aachen University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christian Trautwein, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Uniklinik RWTH Aachen, Med. Klinik III

Locations

Medical University of Vienna

Vienna, , Austria

University Hospital RWTH Aachen

Aachen, , Germany

Sahlgrenska University Hospital

Gothenburg, , Sweden

Countries

Austria; Germany; Sweden

Other Identifiers

17-105

Identifier Type: -

Identifier Source: org_study_id