Clinical trial NCT06377631: Effect of Multi-ingredient on Visceral Adiposity & Non-alcoholic Fatty Liver Disease in Postmenopausal Women 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 Postmenopausal Women With Abdominal Obesity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Visceral Obesity
Non-alcoholic Fatty Liver
Postmenopausal
Keywords: Nutraceuticals
Metabolic risk
Visceral obesity
NAFLD
Hepatic steatosis
Lipid metabolism
Cardiovascular risk
Postmenopause
Histidine
Lead sponsor: Fundació Eurecat
Sponsor class: OTHER
Collaborators: name: Centre de Diagnosi per la Imatge
name: Instituto de Investigación Biomédica de Girona (IDIBGI)
name: Laboratorio de Referencia de Cataluña
First posted: 2024-04-22
Enrollment: 50
Sex: FEMALE
Minimum age (years): 50
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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).

Eligibility criteria: 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.

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: Height (cm)
timeFrame: At baseline
measure: Age
timeFrame: At day -7 (pre-selection visit)
measure: Ethnicity
timeFrame: At day -7 (pre-selection visit)
measure: Change in Body 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 Hip circumference (cm)
timeFrame: Change from Baseline hip 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 Waist-to-Hip ratio
timeFrame: Change from Baseline Waist-to-Hip ratio at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in Lipid Accumulation Product (LAP)
timeFrame: Change from Baseline Lipid Accumulation Product ratio 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 heart rate (bpm)
timeFrame: Change from Baseline Heart rate at 6 and 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 Acylcarnitine levels in blood (umol/L)
timeFrame: Change from Baseline Acylcarnitine levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in 17-beta-estradiol (E2) levels in blood (pg/mL)
timeFrame: Change from Baseline 17-beta-estradiol (E2) levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in Follicle-stimulating hormone (FSH) levels in blood (mU/mL)
timeFrame: Change from Baseline FSH 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 lipidomic profile
timeFrame: Change from Baseline Lipidomic profile at 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 in the expression of lipid-metabolism genes in PBMC
timeFrame: Change from Baseline gene expression 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: Concomitant medication
timeFrame: At day -7 (pre-selection visit), day 1 (visit V1), day 43 (visit 2) and day 85 (visit 3)
measure: Consumption of dietary supplements
timeFrame: At day -7 (pre-selection visit), day 1 (visit V1), day 43 (visit 2) and day 85 (visit 3)
measure: Change in the Supraclavicular skin temperature
timeFrame: Change from Baseline Supraclavicular skin temperature at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Change in postmenopausal symptoms
timeFrame: Change from Baseline postmenopausal symptoms at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)
measure: Adverse events
timeFrame: At 6 weeks (V2) and at 12 weeks (V3) for each of the two treatments (multi-ingredient and placebo)
Other outcomes:
Locations:
city: Reus
country: Spain
facility: Anna Crescenti
state: Catalonia. Spain
city: Reus
country: Spain
facility: Fundació Eurecat
state: Tarragona
Study officials:
affiliation: Fundació Eurecat
name: Antoni Caimari, PhD
role: PRINCIPAL_INVESTIGATOR
References: