Clinical trial NCT05807204: Effect of a Multi-ingredient on Visceral Adiposity and Non-alcoholic Fatty Liver Disease in Individuals With Abdominal Obesity
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Visceral Obesity
Non-Alcoholic Fatty Liver Disease
Keywords: Nutraceuticals
Visceral Obesity
NAFLD
Metabolic risk
L-histidine
L-serine
N-Acetylcysteine
L-carnosine
Glucose metabolism
Lipid metabolism
Hepatic steatosis
Hypertension
Lead sponsor: Fundació Eurecat
Sponsor class: OTHER
Collaborators: name: Centre de Diagnosi per la Imatge
name: Laboratorio de Referencia Sud
name: Centro OWLiver
First posted: 2023-04-11
Enrollment: 20
Sex: MALE
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Visceral Adiposity
timeFrame: Change from Baseline Visceral Adiposity at 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary outcomes:
measure: Change in Hepatic Steatosis
timeFrame: Change from Baseline Hepatic Steatosis at 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Height (cm)
timeFrame: At Baseline
measure: Change in Weight (kg)
timeFrame: Change from Baseline Weight at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in Body Mass Index (BMI) (Kg/m^2)
timeFrame: Change from Baseline Body Mass Index at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in Neck circumference (cm)
timeFrame: Change from Baseline Neck circumference at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in Arm circumference (cm)
timeFrame: Change from Baseline Arm circumference at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in Waist circumference (cm)
timeFrame: Change from Baseline Waist circumference at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in Conicity Index
timeFrame: Change from Baseline Conicity Index at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in Systolic Blood Pressure (mm Hg)
timeFrame: Change from Baseline Systolic Blood Pressure at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in Diastolic Blood Pressure (mm Hg)
timeFrame: Change from Baseline Systolic Blood Pressure at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in intestinal microbiota composition
timeFrame: Change from Baseline intestinal microbiota composition at 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change of biomarkers of oxidative stress (8-OHdG, F2-isoprostanes)
timeFrame: Change from Baseline biomarkers of oxidative stress at 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in serum glucose levels (mg/dL)
timeFrame: Change from Baseline serum glucose levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in serum total cholesterol (mg/dL)
timeFrame: Change from Baseline serum total cholesterol at 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in serum high-density lipoprotein cholesterol (HDL-C,mg/dL)
timeFrame: Change from Baseline serum high-density lipoprotein cholesterol at 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in serum low-density lipoprotein cholesterol (LDL-C, mg/dL)
timeFrame: Change from Baseline serum low-density lipoprotein cholesterol at 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in serum triglycerides (TG, mg/dL)
timeFrame: Change from Baseline serum triglycerides at 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in serum alanine aminotransferase (ALT, U/L)
timeFrame: Change from Baseline serum alanine aminotransferase at 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in serum aspartate aminotransferase (AST, U/L)
timeFrame: Change from Baseline serum aspartate aminotransferase at 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in serum gamma glutamyl transferase (GGT, U/L)
timeFrame: Change from Baseline serum gamma glutamyl transferase at 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in serum insulin levels (mU/L)
timeFrame: Change from Baseline serum insulin levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in serum leptin levels (pg/mL)
timeFrame: Change from Baseline serum leptin levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in serum adiponectin levels (ng/mL)
timeFrame: Change from Baseline serum adiponectin levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in Adiponectin/Leptin ratio (numerical ratio)
timeFrame: Change from Baseline Adiponectin/Leptin ratio at 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in serum Monocyte chemoattractant protein-1 (MCP-1) levels (pg/mL)
timeFrame: Change from Baseline serum MCP-1 levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in plasma tumor necrosis factor alpha (TNF-alpha) levels (pg/mL)
timeFrame: Change from Baseline plasma TNF-alpha levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in plasma Interleukin 6 (IL-6) levels (pg/mL)
timeFrame: Change from Baseline plasma IL-6 levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in plasma Interleukin 10 (IL-10) levels (pg/mL)
timeFrame: Change from Baseline plasma IL-10 levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in plasma Intercellular Adhesion Molecule 1 (ICAM-1) levels (ng/mL)
timeFrame: Change from Baseline plasma ICAM-1 levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in plasma Cluster of Differentiation 14 (CD14) levels (pg/mL)
timeFrame: Change from Baseline plasma CD14 levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in plasma oxidized low density lipoproteins (LDLox) levels (mU/L)
timeFrame: Change from Baseline plasma LDLox levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in serum C-Reactive protein levels (mg/L)
timeFrame: Change from Baseline serum C-Reactive protein levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in Histidine levels in blood (umol/L)
timeFrame: Change from Baseline Histidine levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in Homeostatic Model Assessment from Insulin Resistance Index (HOMA-IR)
timeFrame: Change from Baseline HOMA-IR at 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in Fatty Liver Index (FLI)
timeFrame: Change from Baseline FLI at 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in Triglyceride glucose index (TyG)
timeFrame: Change from Baseline TyG at 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in Plasma atherogenic index
timeFrame: Change from Baseline Plasma atherogenic index at 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in Dietary habits
timeFrame: Change from Baseline Dietary habits at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in Physical activity
timeFrame: Change from Baseline Physical activity at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in concomitant medication
timeFrame: Change from Baseline concomitant medication at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in the consumption of food supplements
timeFrame: Change from Baseline consumption of food supplements at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Analysis of genetic polymorphisms
timeFrame: 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)
measure: Change of Food Intake Biomarkers
timeFrame: Change from Baseline Food Intake Biomarkers at 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Adverse events
timeFrame: After 6 (V2) and 12 weeks (V3) of treatment period for each of the two treatments (multi-ingredient and placebo)
Other outcomes:
Locations:
city: Reus
country: Spain
facility: Eurecat
Study officials:
affiliation: Eurecat, Technology Centre of Catalonia
name: Xavier Escoté, PhD
role: PRINCIPAL_INVESTIGATOR
References: