Effect of a Multi-ingredient on Visceral Adiposity and Non-alcoholic Fatty Liver Disease in Individuals With Abdominal Obesity

Non-Alcoholic Fatty Liver Disease Clinical Trial

— FATHIS  

Official title:

Effect of a Multi-ingredient of L-Histidine, L-Serine, L-Carnosine and N-Acetylcysteine on Visceral Adiposity and Non-alcoholic Fatty Liver Disease in Individuals With Abdominal Obesity. Randomized, Parallel, Placebo Controlled, Triple Blind Study.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05807204
• Other study ID #: FATHIS
• Status: Completed
• Phase: N/A
• Start date: May 1, 2023
• Est. completion date: January 11, 2024

Study information

• Verified date: February 2024
• Source: Fundació Eurecat
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to validate the efficacy of specific combination of different natural histidine-related amino acids in the reduction of visceral fat and liver steatosis, as well their associated comorbidities, in individuals with abdominal obesity.

Description:

World Health Organization (WHO) defines obesity as an excess of fat accumulation in adipose tissues and in other metabolic organs, leading to serious health implications. Obesity is a rising issue whose prevalence has defined as a global pandemic or globesity (>30% world population) being responsible of millions of deaths annually. Also, obesity is related with several comorbidities such as non-alcoholic fatty liver disease (NAFLD), with a global prevalence of >25%. Thus, strategies to ameliorate obesity and NAFLD are critical to improve life expectancy and quality of life and to reduce the economic burden of both diseases.

Current therapies against obesity are mainly focused on weight loss, including lifestyle intervention, to modify eating behaviours and to promote physical activity. However, the compliance of patients with these therapies is small. In addition, there are some drugs to fight against these diseases. In obesity, these medical therapies are focused to decrease fat gastrointestinal absorption using lipase inhibitors with several side effects: faecal incontinence, abdominal cramping and raise in blood pressure. In NAFLD, medical therapies are designed to reduce insulin resistance, using pioglitazone and metformin. However, the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) recommend avoiding pioglitazone use by its relationship with heart failure and cancer, and metformin provides just a modest improvement in NAFLD.

Thus, the finding of new and efficient therapeutic agents is highly desirable to combat these global diseases.

The main objective of this study is to evaluate the effect of daily intake of a specific combination of L-histidine, L-serine, L-carnosine and N-Acetylcysteine, in combination with dietary recommendations, on the amount of visceral fat in individuals with abdominal obesity.

The secondary objectives of this study are to evaluate the effect of daily intake of the multi-ingredient aforementioned in liver fat content and obesity related comorbidities.

Participants who fulfilled the inclusion and exclusion criteria will be randomly assigned to the intervention and control group.

During the study there will be 4 visits: a preselection visit (V0; day -7) and 3 study visits during the consumption of the treatments, which will take place on the first day of the study (V1; day 1 +/- 3 days; week 1), at 6 weeks of treatment (V2; day 44 +/- 3 day; week 6) and at 12 weeks of treatment (V3; day 90 +/- 3 days; week 12).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: January 11, 2024
• Est. primary completion date: December 20, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Men older than 40 years.

• BMI =30.0 kg/m^2 and =35.0 kg/m^2

• Waist circumference =102 cm.

• Read, write and speak Catalan or Spanish.

• Sign the informed consent.

Exclusion Criteria:

• Present values of body mass index > 35 kg/m^2

• Present values of waist circumference > 150 cm.

• Present diabetes.

• Present dyslipidemia (LDL cholesterol = 189 mg/dL and/or triglycerides = 350 mg/dL).

• Present anemia.

• Taking supplements, multivitamin supplements or phytotherapeutic products that interfere with the treatment under study.

• Consume 4 or more Standard Beverage Units (SBU) daily or 28 SBU weekly.

• Be a smoker.

• Present any diagnosed liver disease other than NAFLD.

• Have lost more than 3 kg of weight in the last 3 months.

• Present food intolerances and/or allergies related to the study products, such as hypersensitivity to maltodextrin or N-Acetylcysteine.

• Presenting any chronic or autoimmune disease in clinical manifestation such as hepatitis, hyper or hypothyroidism or metabolic diseases.

• Follow a pharmacological treatment with immunosuppressants, cytotoxic agents, corticosteroids or other drugs that could cause hepatic steatosis or alter the measurements in the liver.

• Being participating or having participated in a clinical trial or nutritional intervention study in the last 30 days before inclusion in the study.

• Follow a hypocaloric diet and/or pharmacological treatment for weight loss.

• Suffering from eating behavior disorders or psychiatric disorders.

• Being unable to follow study guidelines.

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Non-Alcoholic Fatty Liver Disease
• Obesity
• Obesity, Abdominal
• Visceral Obesity

Intervention

Dietary Supplement:
• Multi-ingredient of L-histidine, L-serine, L-carnosine and N-Acetylcysteine
The product will be presented in powder format in a single container and with a measuring spoon of the daily dose.
• Placebo
The product will be presented in powder format in a single container and with a measuring spoon of the daily dose.

Locations

Country	Name	City	State
Spain	Eurecat	Reus

Sponsors (4)

Lead Sponsor	Collaborator
Fundació Eurecat	Centre de Diagnosi per la Imatge, Centro OWLiver, Laboratorio de Referencia Sud

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Visceral Adiposity	Visceral fat content measured using a dual energy x-ray absorptiometry (DXA) scanner	Change from Baseline Visceral Adiposity at 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in Hepatic Steatosis	Liver steatosis will be qualitative determined by ultrasound	Change from Baseline Hepatic Steatosis at 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Height (cm)	Height measured with standardized method	At Baseline
Secondary	Change in Weight (kg)	Weight measured with standardized method	Change from Baseline Weight at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in Body Mass Index (BMI) (Kg/m^2)	Weight and height will be combined to report BMI in kg/m^2	Change from Baseline Body Mass Index at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in Neck circumference (cm)	Neck circumference using a measuring tape	Change from Baseline Neck circumference at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in Arm circumference (cm)	Arm circumference using a measuring tape	Change from Baseline Arm circumference at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in Waist circumference (cm)	Waist circumference using a measuring tape	Change from Baseline Waist circumference at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in Conicity Index	Weight, height and waist circumference will be combined to report Conicity index.	Change from Baseline Conicity Index at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in Systolic Blood Pressure (mm Hg)	Systolic blood pressure will be measured using an automatic sphygmomanometer	Change from Baseline Systolic Blood Pressure at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in Diastolic Blood Pressure (mm Hg)	Diastolic blood pressure will be measured using an automatic sphygmomanometer	Change from Baseline Systolic Blood Pressure at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in intestinal microbiota composition	Metagenomic analysis in fecal samples. The bacteria DNA will be extracted and massive sequenced by the Ion Torrent platform.	Change from Baseline intestinal microbiota composition at 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change of biomarkers of oxidative stress (8-OHdG, F2-isoprostanes)	Biomarkers of oxidative stress will be evaluated in urine by standardized chemiluminescence methods	Change from Baseline biomarkers of oxidative stress at 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in serum glucose levels (mg/dL)	Serum glucose levels will be determined by standardized spectrophotometry methods	Change from Baseline serum glucose levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in serum total cholesterol (mg/dL)	Total cholesterol will be determined by standardized spectrophotometry methods	Change from Baseline serum total cholesterol at 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in serum high-density lipoprotein cholesterol (HDL-C,mg/dL)	High-density lipoprotein cholesterol will be determined by standardized spectrophotometry methods	Change from Baseline serum high-density lipoprotein cholesterol at 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in serum low-density lipoprotein cholesterol (LDL-C, mg/dL)	Low-density lipoprotein cholesterol will be calculated using the Friedewald formula	Change from Baseline serum low-density lipoprotein cholesterol at 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in serum triglycerides (TG, mg/dL)	Triglycerides will be determined by standardized spectrophotometry methods	Change from Baseline serum triglycerides at 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in serum alanine aminotransferase (ALT, U/L)	Alanine aminotransferase will be determined by standardized spectrophotometry methods	Change from Baseline serum alanine aminotransferase at 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in serum aspartate aminotransferase (AST, U/L)	Aspartate aminotransferase will be determined by standardized spectrophotometry methods	Change from Baseline serum aspartate aminotransferase at 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in serum gamma glutamyl transferase (GGT, U/L)	Gamma glutamyl transferase will be determined by standardized spectrophotometry methods	Change from Baseline serum gamma glutamyl transferase at 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in serum insulin levels (mU/L)	Insulin levels will be measured by standardized chemiluminescence methods.	Change from Baseline serum insulin levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in serum leptin levels (pg/mL)	Leptin levels will be measured by standardized chemiluminescence methods	Change from Baseline serum leptin levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in serum adiponectin levels (ng/mL)	Adiponectin levels will be measured by standardized chemiluminescence methods	Change from Baseline serum adiponectin levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in Adiponectin/Leptin ratio (numerical ratio)	Adiponectin and leptin will be combined to report adiponectin/leptin ratio	Change from Baseline Adiponectin/Leptin ratio at 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in serum Monocyte chemoattractant protein-1 (MCP-1) levels (pg/mL)	MCP-1 levels will be measured by standardized chemiluminescence methods	Change from Baseline serum MCP-1 levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in plasma tumor necrosis factor alpha (TNF-alpha) levels (pg/mL)	TNF-alpha levels will be measured by standardized chemiluminescence methods	Change from Baseline plasma TNF-alpha levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in plasma Interleukin 6 (IL-6) levels (pg/mL)	IL-6 levels will be measured by standardized chemiluminescence methods	Change from Baseline plasma IL-6 levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in plasma Interleukin 10 (IL-10) levels (pg/mL)	IL-10 levels will be measured by standardized chemiluminescence methods	Change from Baseline plasma IL-10 levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in plasma Intercellular Adhesion Molecule 1 (ICAM-1) levels (ng/mL)	ICAM-1 levels will be measured by standardized chemiluminescence methods	Change from Baseline plasma ICAM-1 levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in plasma Cluster of Differentiation 14 (CD14) levels (pg/mL)	CD14 levels will be measured by standardized chemiluminescence methods	Change from Baseline plasma CD14 levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in plasma oxidized low density lipoproteins (LDLox) levels (mU/L)	LDLox levels will be measured by standardized chemiluminescence methods	Change from Baseline plasma LDLox levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in serum C-Reactive protein levels (mg/L)	C-Reactive protein levels will be determined by standardized spectrophotometry methods	Change from Baseline serum C-Reactive protein levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in Histidine levels in blood (umol/L)	Serum histidine levels will be determined by Liquid Chromatography coupled to tandem Mass Spectrometry	Change from Baseline Histidine levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in Homeostatic Model Assessment from Insulin Resistance Index (HOMA-IR)	HOMA-IR will be calculated using serum glucose and insulin levels.	Change from Baseline HOMA-IR at 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in Fatty Liver Index (FLI)	FLI will be calculated using BMI, waist circumference, serum triglycerides and gamma glutamyl transferase levels	Change from Baseline FLI at 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in Triglyceride glucose index (TyG)	TyG will be calculated using serum glucose and triglycerides levels	Change from Baseline TyG at 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in Plasma atherogenic index	Plasma atherogenic index will be calculated as the logarithm of the TG to HDL-c ratio	Change from Baseline Plasma atherogenic index at 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in Dietary habits	Nutritional habits will be determined based on the results obtained from the 3-day dietary record.	Change from Baseline Dietary habits at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in Physical activity	Physical activity will be evaluated through the International Physical Activity Questionnaire (IPAQ)-short for physical activity questionnaire	Change from Baseline Physical activity at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in concomitant medication	The consumption of concomitant medication by the volunteers will be controlled by the record of concomitant medication in the case report form	Change from Baseline concomitant medication at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in the consumption of food supplements	The consumption of food supplements by the volunteers will be controlled by the record of food supplements in the case report form	Change from Baseline consumption of food supplements at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Analysis of genetic polymorphisms	Single Nucleotide Polymorphisms (SNPs) in saliva samples will be analysed by Illumina sequencing	Single nucleotide polymorphisms (SNPs) in loci of genetic susceptibility to abdominal adiposity will be studied at 12 weeks after treatment for each of the two treatments (multi-ingredient and placebo)
Secondary	Change of Food Intake Biomarkers	Food Intake biomarkers will be evaluated in urine using Metabolomics analyses (UHPLC MS)	Change from Baseline Food Intake Biomarkers at 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Adverse events	Possible adverse events derived from taking study's products will be recorded in the case report form	After 6 (V2) and 12 weeks (V3) of treatment period for each of the two treatments (multi-ingredient and placebo)

External Links

•   Technological Centre of Nutrition and Health. Eurecat_Reus