Impact of a Specific Micronutrient-probiotic-supplement on Fatty Liver of Patients After Mini-Gastric Bypass Surgery (FMG-01)

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

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.

Study Overview

• Status: Completed
• Conditions: Obesity; NAFLD; Gastric Bypass
• Intervention / Treatment: Dietary supplement: Micronutrient-probiotic-combination; Dietary supplement: Micronutrient-placebo-combination

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Cologne, Germany, 50825
    • St. Franziskus-Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Specific Micronutrient-probiotic-combination; 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; Specific combined micronutrient-probiotic-supplement with different vitamins, minerals, phytochemicals and bioactive substances, and a mixture of 10 different probiotic bacteria.
Placebo Comparator: Micronutrient-placebo-combination; 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; micronutrient (capsule)-placebo (powder)-supplement

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Bonn Education Association for Dietetics r.A., Cologne, Germany
• Collaborators: St. Franziskus Hospital; University of Bonn; FormMed HealthCare AG
• Investigators: Principal Investigator: Karl Peter Rheinwalt, MD, St. Franziskus Hospital, Cologne and Bonn Education Association for Dietetics r.A., Cologne, Germany

Publications and helpful links

General Publications

• Crommen S, Rheinwalt KP, Plamper A, Simon MC, Rosler D, Fimmers R, Egert S, Metzner C. A Specifically Tailored Multistrain Probiotic and Micronutrient Mixture Affects Nonalcoholic Fatty Liver Disease-Related Markers in Patients with Obesity after Mini Gastric Bypass Surgery. J Nutr. 2022 Feb 8;152(2):408-418. doi: 10.1093/jn/nxab392.

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2018
• Primary Completion (Actual): January 17, 2020
• Study Completion (Actual): January 17, 2020

Study Registration Dates

• First Submitted: June 7, 2018
• First Submitted That Met QC Criteria: July 11, 2018
• First Posted (Actual): July 13, 2018

Study Record Updates

• Last Update Posted (Actual): September 25, 2020
• Last Update Submitted That Met QC Criteria: September 23, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Obesity; Bariatric surgery; NAFLD; Micronutrient supplementation; Probiotic supplementation
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Physiological Effects of Drugs; Micronutrients; Trace Elements
• Other Study ID Numbers: BFD-02/FMG-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No