Clinical trial NCT03585413: Impact of a Specific Micronutrient-probiotic-supplement on Fatty Liver of Patients After Mini-Gastric Bypass Surgery
Official title: Impact of a Specific Micronutrient-probiotic-combination on Fatty Liver and Cardiometabolic Status of Obese Patients After Mini-Gastric Bypass Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Obesity
Gastric Bypass
NAFLD
Keywords: Bariatric surgery
Obesity
NAFLD
Micronutrient supplementation
Probiotic supplementation
Lead sponsor: Bonn Education Association for Dietetics r.A., Cologne, Germany
Sponsor class: INDUSTRY
Collaborators: name: St. Franziskus Hospital
name: University of Bonn
name: FormMed HealthCare AG
First posted: 2018-07-13
Enrollment: 60
Sex: ALL
Minimum age (years): 20
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: prospective, randomized, placebo-controlled, double-blind interventional study
Primary purpose: TREATMENT

Brief summary: 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: 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).

Eligibility criteria: 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

Primary outcomes:
measure: Change in alanine-aminotransferase (ALAT) activity in serum
timeFrame: Baseline and 12 weeks
Secondary outcomes:
measure: Change in Fatty Liver Index (FLI)
timeFrame: Baseline and 12 weeks
measure: Change in nonalcoholic fatty liver disease (NAFLD) Fibrosis Score (NFS)
timeFrame: Baseline and 12 weeks
measure: Change in fasting glucose concentration
timeFrame: Baseline and 12 weeks
measure: Change in fasting insulin concentration
timeFrame: Baseline and 12 weeks
measure: Change in homeostatic model assessment (HOMA) of insulin resistance (IR) (HOMA-IR)
timeFrame: Baseline and 12 weeks
measure: Change in glycated haemoglobin (HbA1c)
timeFrame: Baseline and 12 weeks
measure: Change in resting blood pressure
timeFrame: Baseline and 12 weeks
measure: Change in heart rate
timeFrame: Baseline and 12 weeks
Other outcomes:
Locations:
city: Cologne
country: Germany
facility: St. Franziskus-Hospital
Study officials:
affiliation: St. Franziskus Hospital, Cologne and Bonn Education Association for Dietetics r.A., Cologne, Germany
name: Karl Peter Rheinwalt, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.