Impact of a Specific Micronutrient-probiotic-supplement on Fatty Liver of Patients After Mini-Gastric Bypass Surgery

Study Overview
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Brief Summary
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Aim of this prospective randomized intervention study is to evaluate the effect of a dietary intervention with a specific micronutrient-probiotic-combination for 12 weeks on fatty liver and cardiometabolic status in obese, nonalcoholic fatty liver disease (NAFLD) patients after Mini-Gastric Bypass (MGB) surgery.

Detailed Description
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Background: The increasing prevalence of obesity and diabetes mellitus seems to reach epidemic proportions worldwide. In particular visceral obesity in combination with impaired glucose tolerance is associated with risk for progression of a broad spectrum of cardiometabolic diseases such as type 2 diabetes, hypertension, dyslipidemia, cardiovascular disease and non-alcoholic fatty liver disease (NAFLD). Thus, among patients undergoing bariatric surgery more than 95% have NAFLD, with nonalcoholic steatohepatitis (NASH) being present in 32-39 %. Only bariatric surgery currently seems to attain long-term weight loss in morbidly obese patients. In addition, greater success in terms of improvement in obesity related comorbidities and reduction of overall-mortality can be achieved by surgical measures. Recent data indicate that Mini-Gastric Bypass (MGB) is an effective procedure for weight loss and reduction of comorbidities. Although weight loss is usually recommended as therapy for obesity with NAFLD and NASH, not all NAFLD patients benefit from surgical induced weight loss as indicated by increase in transaminase activity. An optimized micronutrient in combination with a probiotic supplementation could be a useful tool to prevent the transition from NAFLD to NASH. Aim: Therefore this study aims to elucidate the effect of a specific micronutrient-probiotic-combination on fatty liver and insulin resistance in obese patients after MGB surgery. Furthermore, this study aims to help optimizing the dietary food supplementation after MGB to reduce the progress of NAFLD/NASH and cardiometabolic diseases. Methods: A randomized double blind clinical trial of 12 week dietary intervention with a specific micronutrient-probiotic-combination will be conducted in obese patients with NAFLD after standardized MGB surgery. To this end, a total of 60 patients will be randomly assigned to a specific micronutrient-probiotic-combination or micronutrient-placebo-combination group. During the preoperative 4-week run-in phase, each patient receives a formula diet to improve protein and micronutrient supply. This should align the metabolic situation within the study group. At baseline and study end blood samples are taken for further analysis of metabolic, clinical and biochemical parameters. Anthropometric data (body height, body weight, and waist circumference) and bioelectrical impedance analysis are also collected at the beginning and after 8 and 12 weeks. Fecal samples will be collected prior to surgery and after 4, 8 and 12 weeks (concomitant variable). All patients will fill out validated food intake questionnaires and stool questionnaires (frequency and consistence) after 4, 8 and 12 weeks (concomitant variable).

Official Title
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Impact of a Specific Micronutrient-probiotic-combination on Fatty Liver and Cardiometabolic Status of Obese Patients After Mini-Gastric Bypass Surgery

Conditions
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Obesity, Gastric Bypass, NAFLD

Intervention / Treatment
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* Dietary Supplement: Micronutrient-probiotic-combination
* Dietary Supplement: Micronutrient-placebo-combination


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: subjects 20-65 years old BMI ≥ 35 kg/m² to ≤ 50 kg/m² Fatty Liver Index ≥ 60 Exclusion Criteria: subjects with anamnestic known alcoholic-fatty liver disease, hepatitis B, hepatitis C, HIV/ AIDS subjects with chronic conditions such as active malignant disease, inflammatory bowel disease and other systemic inflammatory conditions supplementation with dietary supplements or drugs which contain probiotics, milk thistle, fatty acids, vitamins or minerals 4 weeks before bariatric surgery treatment with psychotropic drugs diabetic patients who are treated with antidiabetic medications use of antibiotic 4 weeks before bariatric surgery weight gain during run-in phase of more than 5 % in women of childbearing age, pregnancy or breastfeeding no safe method of contraception in women of childbearing age

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: prospective, randomized, placebo-controlled, double-blind interventional study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Specific Micronutrient-probiotic-combination<br>Intake of one micronutrient capsule three times daily and probiotic powder twice daily starting on the first day after hospital discharge until 12 weeks postoperatively. The micronutrient capsules consist of vitamins, minerals, phytochemicals and bioactive substances. The probiotic supplement is a powder of 10 different species of probiotic bacteria. | Dietary Supplement: Micronutrient-probiotic-combination<br>* Specific combined micronutrient-probiotic-supplement with different vitamins, minerals, phytochemicals and bioactive substances, and a mixture of 10 different probiotic bacteria.<br>|
| Placebo Comparator: Micronutrient-placebo-combination<br>Intake of one micronutrient capsule three times daily and placebo powder twice daily starting on the first day after hospital discharge until 12 weeks postoperatively. The micronutrient-control-combination consists of a micronutrient capsule (vitamins and minerals) but without phytochemicals and bioactive substances, and a placebo powder manufactured to mimic the probiotic powder. | Dietary Supplement: Micronutrient-placebo-combination<br>* micronutrient (capsule)-placebo (powder)-supplement<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in alanine-aminotransferase (ALAT) activity in serum | ALAT in U/l | Baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Fatty Liver Index (FLI) | FLI will be calculated as: [e 0.953 x loge (triglycerides (mg/dl)) + 0.139 x BMI (kg/m²) + 0.718 x loge (GGT (U/l)) + 0.053 x waist circumference (cm) - 15.745) / (1 + e 0.953 x loge (triglycerides (mg/dl)) + 0.139 x BMI (kg/m²) + 0.718 x loge (GGT (U/l)) + 0.053 x waist circumference (cm) - 15.745)] × 100. A FLI < 30 rules out fatty liver and a FLI > 60 rules in fatty liver. | Baseline and 12 weeks | 
| Change in nonalcoholic fatty liver disease (NAFLD) Fibrosis Score (NFS) | NFS will be calculated as: - 1.675 + 0.037 x age (years) + 0.094 x BMI (kg/m²) + 1.13 x impaired fasting glucose (IFG)/diabetes (yes = 1, no = 0) + 0.99 x aspartate aminotransferase (ASAT)/ALAT ratio - 0.013 x platelet (x10^9) - 0.66 x albumin (g/dl). NFS > 0.676 is considered to be diagnostic for the presence of significant fibrosis. NFS < -1.455 is considered to be diagnostic fot the absence if fibrosis. NFS scores between -1.455 and 0.675 are referred as indeterminate scores. | Baseline and 12 weeks | 
| Change in fasting glucose concentration | Fasting glucose in mmol/l | Baseline and 12 weeks | 
| Change in fasting insulin concentration | Fasting insulin in pmol/l | Baseline and 12 weeks | 
| Change in homeostatic model assessment (HOMA) of insulin resistance (IR) (HOMA-IR) | HOMA-IR will be calculated as: fasting insulin (μU/ml) x fasting glucose (mmol/l) / 22.5. HOMA-IR > 2.77 is considered to be diagnostic for insulin resistance. | Baseline and 12 weeks | 
| Change in glycated haemoglobin (HbA1c) | Intervention change in HbA1c level | Baseline and 12 weeks | 
| Change in resting blood pressure | Intervention changes in resting blood pressure in mmHg | Baseline and 12 weeks | 
| Change in heart rate | Intervention changes in heart rate in bpm | Baseline and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bariatric surgery, Obesity, NAFLD, Micronutrient supplementation, Probiotic supplementation