Effect of Fucoxanthin on the Metabolic Syndrome, Insulin Sensitivity and Insulin Secretion

Study Overview
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Brief Summary
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The Metabolic Syndrome (MS) is a cluster of cardiometabolic risk factors, which include abdominal obesity, hyperglycemia, dyslipidemia, and high blood pressure. MS is considered a serious problem to health systems due to a current inability on implementing an effective prevention and treatment program. In Mexico 73% of adult population suffers obesity or overweight, this condition triggers the best studied pathophysiological mechanism; insulin resistance, which in turn precedes the diagnosis of diabetes and cardiovascular disease, that are the main cause of general mortality in Mexico, thus the prevention and timely treatment of this condition are now a priority. Actual pharmacological therapy is designed to control its components individually, however, there are great interest in developing new therapeutic lines that improve more than one component simultaneously and thereby increase the cost-benefit and effectiveness of the therapy. Fucoxanthin is a functional element present in seaweed species. Several studies have offered certain perspectives on its action mechanism and safety. The information available is favorable for weight control in overweight subjects, but its activity in glucose levels, lipid metabolism and blood pressure is inconsistent. It represents a natural option with great interest in this research, since it could be a new, safe and effective therapy in the MS. The aim of this study is to evaluate the effect of fucoxanthin on the components of the MS, insulin sensitivity and insulin secretion. The investigators hypothesis is that Fucoxanthin modifies the components of the MS, insulin sensitivity and insulin secretion

Detailed Description
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A randomized, double-blind, placebo-controlled, clinical trial will be conducted in 28 patients with MS according to the International Diabetes Federation (IDF) criteria, men and women, ages 30 to 60. Participants will be assigned randomly into two groups of 14 individuals each. Patients will receive a capsule with Fucoxanthin 12 mg or homologated placebo once a day during 90 days. Waist circumference, fasting blood glucose, serum triglycerides, serum HDL cholesterol and blood pressure will be evaluated before and after intervention in both groups. First phase of insulin secretion (Stumvoll index), total insulin secretion (Insulinogenic index) and Insulin sensitivity (Matsuda index) will be calculated from the concentration of glucose and insulin obtained from an Oral Glucose Tolerance Test. Data from statistical analysis will be presented through measures of central tendency and dispersion( mean and standard deviation) for quantitative variables and frequencies and percentages for qualitative variables. The qualitative variables will be analyzed through the X2 or Fisher's exact test. The intra-group analysis of the quantitative variables will be carried out by means of the Wilcoxon rank test, while the inter-group analysis with the U test of Mann Whitney and Kruskal-Wallis. Statistical significance will be considered with a p<0.05. This protocol was approved by a local ethics committee and written informed consent will be obtained from all volunteers

Official Title
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Effect of Fucoxanthin on the Metabolic Syndrome, Insulin Sensitivity and Insulin Secretion

Conditions
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Metabolic Syndrome

Intervention / Treatment
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* Drug: Fucoxanthin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed MS according to the IDF criteria: - - Waist circumference: ≥80 cm (women) ≥90 cm (men), plus two or more of the following: - - - - Fasting glucose ≥ 100 mg/dL - - - - Triglycerides ≥150 mg/dL - - - - HDL-C: Men ≤40 mg/dL, women ≤50 mg/dL - - - - Blood pressure ≥130/85 mmHg Body Mass Index between 25 and 34.9 kg/m² No pharmacological treatment for MS Stable weight during the last 3 months Exclusion Criteria: Pregnancy or breast-feeding History of kidney or liver disease Drugs or supplements consumption with proven properties that modify the behavior of the MS Total cholesterol >240 mg/dL Triglycerides >500mg/dL Glucose ≥126 mg/dL or HbA1C ≥6.5%. Hypersensitivity to Fucoxanthin

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fucoxanthin<br>12 mg Fucoxanthin capsule, once a day before breakfast during 90 days. | Drug: Fucoxanthin<br>* Intervention will be administered 30 minutes before breakfast.<br>|
| Placebo Comparator: Placebo<br>Homologated magnesium sterate capsule, once a day before breakfast during 90 days. | Drug: Placebo<br>* Intervention will be administered 30 minutes before breakfast.<br>* Other names: Magnesium Sterate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Baseline Waist Circumference after intervention. | Waist circumference will be measured at baseline, day 30, day 60 and day 90 with a validated metric tape, with the method proposed by ISAK. Values will be expressed in centimeters (cm). | Baseline, Day 30, Day 60 and Day 90. | 
| Changes in Baseline Fasting Serum Glucose level after Intervention. | Fasting serum glucose level will be measured at baseline and day 90 with enzymatic/colorimetric techniques. Values will be expressed in milligrams per deciliter (mg/dL). | Baseline and Day 90. | 
| Changes in Baseline Triglycerides (TG) level after Intervention. | Serum triglycerides level will be measured at baseline and day 90 with enzymatic/colorimetric techniques. Values will be expressed in milligrams per deciliter (mg/dL). | Baseline and Day 90. | 
| Changes in Baseline High-density Lipoprotein (HDL-C) level after Intervention. | Serum HDL-C level will be measured at baseline and day 90 with enzymatic/colorimetric techniques. Values will be expressed in milligrams per deciliter (mg/dL). | Baseline and Day 90. | 
| Changes in Baseline Systolic Blood Pressure level after Intervention. | Systolic blood pressure will be measured at baseline, day 30, day 60 and day 90 with a digital sphygmomanometer. Values will be expressed in millimeters of mercury (mmHg). | Baseline, Day 30, Day 60 and Day 90. | 
| Changes in Baseline Diastolic Blood Pressure level after Intervention. | Diastolic blood pressure will be measured at baseline, day 30, day 60 and day 90 with a digital sphygmomanometer. Values will be expressed in millimeters of mercury (mmHg). | Baseline, Day 30, Day 60 and Day 90. | 
| Changes in Baseline Insulin Sensitivity (Matsuda-DeFronzo insulin sensitivity index) after Intervention. | Insulin sensitivity will be determined at baseline and day 90 with the Matsuda-DeFronzo insulin sensitivity index. Calculated from serum concentrations of insulin (by ELISA) and glucose, obtained during an oral glucose tolerance test (OGTT). A value of <4.3 predict impaired insulin sensitivity. Uses the following formula: Matsuda index = 10,000 / √glucose 0' x insulin 0') (mean glucose oral glucose tolerance test (OGTT) x mean insulin OGTT). | Baseline and Day 90. | 
| Changes in Baseline Total Insulin Secretion (Insulinogenic index) after Intervention. | Total insulin secretion will be determined at baseline and day 90 with Insulinogenic index. Insulinogenic index helps to estimate the total insulin secretion. Calculated from serum concentrations of insulin (by ELISA) and glucose, obtained during an oral glucose tolerance test (OGTT). Using the following formula: Insulinogenic Index = δAUCinsulin/δAUCglucose. | Baseline and Day 90. | 
| Changes in Baseline First Phase of Insulin Secretion (Stumvoll index) after Intervention. | First phase of insulin secretion will be calculated at baseline and day 90 with Stumvoll index. Stumvoll index estimate the first phase of insulin secretion using demographic data in addition to plasma glucose (mmol/L) and insulin (pmol/L) levels obtained during an oral glucose tolerance test (OGTT). Calculated with the following formula: Stumvoll index = 1283+ 1.829 x insulin 30' - 138.7 x glucose 30' + 3.772 x insulin 0'. | Baseline and Day 90. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Baseline Body Weight after Intervention. | Body weight will be measured at baseline, day 30, day 60 and day 90 with a bioimpedance scale. Values will be expressed in kilograms (kg). | Baseline, Day 30, Day 60 and Day 90. | 
| Changes in Baseline Body Mass Index (BMI) after Intervention. | Body Mass Index will be calculated at baseline, day 30, day 60 and day 90 with with the Quetelet index formula, using a bioimpedance scale. Values will be expressed in kilograms per square meter (km/m2). | Baseline, Day 30, Day 60 and Day 90. | 
| Changes in Baseline Percentage of Body Fat after intervention. | Percentage of body fat will be measured at baseline, day 30, day 60 and day 90 with a bioimpedance scale. Values will be expressed in percentages. | Baseline, Day 30, Day 60 and Day 90. | 
| Changes in Baseline Total Cholesterol (TC) level after intervention. | Serum total cholesterol level will be measured at baseline and day 90 with enzymatic/colorimetric techniques. Values will be expressed in milligrams per deciliter (mg/dL). | Baseline and Day 90. | 
| Changes in Baseline Low-density lipoprotein (LDL-C) levels after intervention. | Serum LDL-C level will be calculated at baseline and day 90 with the Friedewald formula: LDL-C = TC - (HDL-C + [TG/5]). Values will be expressed in milligrams per deciliter (mg/dL). | Baseline and Day 90. | 
| Changes in Baseline Very-low-density Lipoprotein (VLDL-C) level after intervention. | Serum VLDL-C level will be calculated at baseline and day 90 with the formula: VLDL-C = TG/5. Values will be expressed in milligrams per deciliter (mg/dL). | Baseline and Day 90. | 
| Changes in Baseline Alanine Aminotransferase (ALT) level after intervention. | Serum alanine aminotransferase level will be measured at baseline and day 90 with enzymatic/colorimetric techniques. Values will be expressed in milligrams per deciliter (mg/dL). | Baseline and Day 90. | 
| Changes in Baseline Aspartate Aminotransferase (AST) level after intervention. | Serum aspartate aminotransferase level will be measured at baseline and day 90 with enzymatic/colorimetric techniques. Values will be expressed in milligrams per deciliter (mg/dL). | Baseline and Day 90. | 
| Changes in Baseline Creatinin level after intervention. | Serum creatinin level will be measured at baseline and day 90 with enzymatic/colorimetric techniques. Values will be expressed in milligrams per deciliter (mg/dL). | Baseline and Day 90. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Insulin Secretion, Insulin Sensitivity, Metabolic Syndrome, Fucoxanthin