Effect of Multi-ingredient on Visceral Adiposity & Non-alcoholic Fatty Liver Disease in Postmenopausal Women With Abdominal Obesity

Postmenopausal 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 Postmenopausal Women With Abdominal Obesity

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06377631
• Other study ID #: FATHIS+
• Status: Not yet recruiting
• Phase: N/A
• Start date: May 2024
• Est. completion date: May 2025

Study information

• Verified date: April 2024
• Source: Fundació Eurecat
• Contact: Xavier Escoté, PhD
• Phone: +34 977 300 431
• Email: xavier.escote[@]eurecat.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to evaluate the effect of daily intake of a specific combination of different natural histidine-related amino acids in combination with dietary recommendations, in the reduction of visceral fat, as well as their associated comorbidities, in postmenopausal women with abdominal obesity.

Description:

In postmenopausal women, the risk of non-alcoholic fatty liver disease (NAFLD) increases due to hormonal changes and metabolic shifts. Menopause leads to a decline in estrogen levels, affecting lipid metabolism and promoting abdominal and visceral fat accumulation. This visceral adiposity poses a significant risk factor for insulin resistance, type 2 diabetes, dyslipidemia, cardiovascular diseases, and NAFLD. While the prevalence of NAFLD is initially higher in men, it becomes comparable or even higher in postmenopausal women due to these metabolic changes.

Studies suggest that estrogen deficiency post-menopause contributes to the development of NAFLD in women. Lower serum estrogen levels are associated with a higher likelihood of NAFLD development, indicating the potential role of hormone replacement therapy (HRT) in mitigating NAFLD risk in postmenopausal women. However, the use of HRT must be carefully evaluated due to potential adverse effects on cardiovascular health.

Thus, novel, effective and safety therapeutic strategies for managing metabolic disorders in postmenopausal women are highly desirable.

The main objective of this study is to evaluate the effect of daily intake of a specific combination of different natural histidine-related amino acids in combination with dietary recommendations, in the reduction of visceral fat in postmenopausal women with abdominal obesity.

The secondary objectives of this study are to evaluate the effect of daily intake of the multi-ingredient aforementioned in liver function markers, anthropometric parameters, blood pressure and heart rate, markers of lipid metabolism, markers of glucidic metabolism, inflammatory markers, histidine serum levels, sexual hormones, the temperature of supraclavicular brown adipose tissue, changes in the intestinal microbiota, changes in the expression of lipid metabolism-related genes and symptoms associated with postmenopause.

A randomized, parallel, placebo-controlled, single-center, triple-blind clinical trial with a 1:1:1 ratio between interventions with 50 participants will be conducted.

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 43 +/- 3 day; week 6) and at 12 weeks of treatment (V3; day 85 +/- 3 days; week 12).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: May 2025
• Est. primary completion date: May 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 50 Years to 65 Years

Eligibility

Inclusion Criteria:

• Postmenopausal women aged 50 to 65 years.

• BMI =27.5 kg/m^2 and =32.5 kg/m^2.

• Waist circumference =88 cm.

• No hormone replacement therapy.

• Read, write and speak Catalan or Spanish.

• Sign the informed consent.

Exclusion Criteria:

• Present values of body mass index < 27.5 kg/m^2 or > 32.5 kg/m^2

• Present values of waist circumference > 115 cm.

• Present diabetes.

• Present dyslipidemia.

• Present anemia.

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

• Consume 2 or more Standard Beverage Units (SBU) daily or 17 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
• Non-alcoholic Fatty Liver Disease
• Obesity
• Obesity, Abdominal
• Postmenopausal
• 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	Anna Crescenti	Reus	Catalonia. Spain

Sponsors (4)

Lead Sponsor	Collaborator
Fundació Eurecat	Centre de Diagnosi per la Imatge, Instituto de Investigación Biomédica de Girona (IDIBGI), Laboratorio de Referencia de Cataluña

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	Height (cm)	Height measured with standardized method	At baseline
Secondary	Age	The age of the volunteers will be recorded in the case report form.	At day -7 (pre-selection visit)
Secondary	Ethnicity	The ethnicity of the volunteers will be recorded in the case report form.	At day -7 (pre-selection visit)
Secondary	Change in Body 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 Hip circumference (cm)	Hip circumference using a measuring tape	Change from Baseline hip 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 Waist-to-Hip ratio	Waist and Hip circumference will be combined to report Waist-to-Hip ratio	Change from Baseline Waist-to-Hip ratio at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in Lipid Accumulation Product (LAP)	Waist circumference and fasting plasma Triglycerides will be combined to report Lipid Accumulation Product	Change from Baseline Lipid Accumulation Product ratio 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 heart rate (bpm)	Heart rate will be measured using an automatic sphygmomanometer	Change from Baseline Heart rate at 6 and 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 Acylcarnitine levels in blood (umol/L)	Serum Acylcarnitine levels will be determined by Liquid Chromatography coupled to tandem Mass Spectrometry	Change from Baseline Acylcarnitine levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in 17-beta-estradiol (E2) levels in blood (pg/mL)	Serum 17-beta-estradiol (E2) levels will be determined by standardized chemiluminescence methods	Change from Baseline 17-beta-estradiol (E2) levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in Follicle-stimulating hormone (FSH) levels in blood (mU/mL)	Follicle-stimulating hormone (FSH) levels will be determined by standardized chemiluminescence methods	Change from Baseline FSH 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 lipidomic profile	Lipidomic analyses will be done by Liquid Chromatography coupled to tandem Mass Spectrometry	Change from Baseline Lipidomic profile at 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 in the expression of lipid-metabolism genes in PBMC	Peripheral blood mononuclear cell (PBMC) will be isolated to obtain the RNA for gene expression analyses by Quantitative reverse transcription PCR (RT-qPCR)	Change from Baseline gene expression 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. Scores will be reported in categories: LOW activity levels, MODERATE activity levels or HIGH activity levels with the latter indicating better outcomes.	Change from Baseline Physical activity at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Concomitant medication	Concomitant medication consumed during the study will be recorded in the case report form.	At day -7 (pre-selection visit), day 1 (visit V1), day 43 (visit 2) and day 85 (visit 3)
Secondary	Consumption of dietary supplements	Dietary supplements consumed during the study will be recorded in the case report form.	At day -7 (pre-selection visit), day 1 (visit V1), day 43 (visit 2) and day 85 (visit 3)
Secondary	Change in the Supraclavicular skin temperature	Supraclavicular skin temperature will be measured with the FLIR T530 thermal imaging camera	Change from Baseline Supraclavicular skin temperature at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)
Secondary	Change in postmenopausal symptoms	Postmenopausal symptoms will be evaluated through the Menopause Rating Scale (MRS) questionnaire. The MRS comprises 11 items representing various symptoms or complaints. Each symptom can be rated from 0 (indicating no complaints) to 4 points (indicating severe symptoms), depending on the perceived severity reported by the women completing the scale. The total MRS score ranges from 0 (asymptomatic) to 44 (maximum complaint severity).	Change from Baseline postmenopausal symptoms at 6 and 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	At 6 weeks (V2) and at 12 weeks (V3) for each of the two treatments (multi-ingredient and placebo)

External Links

•   Technological Centre of Nutrition and Health. Eurecat_Reus.