Healthy Aging Through Functional Food

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether dietary inducers of glyoxalase 1 are effective in improving metabolic and vascular health.

Detailed Description
-----------------
The aim of the study is to evaluate dietary inducers of glyoxalase 1 for effects on metabolic and vascular health in overweight volunteers at risk of developing type 2 diabetes. The research objectives are: (i) To evaluate dietary inducers of glyoxalase 1 for effects on markers of glucose metabolism during an oral glucose tolerance test (oGTT), (ii) To evaluate dietary inducers of glyoxalase 1 for effects on vascular function on three levels, using finger fold capillary density by capillaroscopy (FFCD), arterial stiffness by aortal pulse wave velocity (aPWV) and flow mediated dilatation (FMD); and effects on metabolic and pro-inflammatory markers in circulating blood and urine.

Official Title
-----------------
Dietary Inducers of Glyoxalase-1 for Prevention and Early-stage Alleviation of Age Related Health Disorders Through Functional Foods.

Conditions
-----------------
Glucose Intolerance, Aortic Stiffness, Vasodilation

Intervention / Treatment
-----------------
* Dietary Supplement: Glyoxalase 1 (Glo1) inducer
* Dietary Supplement: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: BMI 25 - 40 kg/m2 (>23 kg/m2 for Asians), with normal, impaired fasting or impaired postprandial glucose. No other relevant morbidities. Women will be preferably post-menopausal. Exclusion Criteria: Severe hypertriglyceridemia. Uncontrolled hypertension, cardiovascular disease, relevant renal or hepatic disease, diabetes, and other relevant morbidity. Excess alcohol consumption, smoking, acute pharmacological treatment with drugs affecting glucose metabolism such as steroids and antibiotics. Anticoagulants. Intake of herbal remedies. Food allergies.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glo1-inducer then placebo<br>Glyoxalase 1 Inducer (8 weeks), then washout (6 weeks), then Placebo (8 weeks). | Dietary Supplement: Glyoxalase 1 (Glo1) inducer<br>* Dietary bioactive<br>* Other names: trans-resveratrol, 90 mg + hesperetin, 120 mg (combination);Dietary Supplement: Placebo<br>* Mannitol, 108 mg<br>|
| Experimental: Placebo then Glo1-inducer<br>Placebo (8 weeks), then washout (6 weeks), then Glyoxalase 1 Inducer (8 weeks). | Dietary Supplement: Glyoxalase 1 (Glo1) inducer<br>* Dietary bioactive<br>* Other names: trans-resveratrol, 90 mg + hesperetin, 120 mg (combination);Dietary Supplement: Placebo<br>* Mannitol, 108 mg<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve for Oral Glucose Tolerance Test (oGGT) | A standard 75 g glucose oGTT will be performed, as routinely used in clinical practice. Participants will be instructed to eat carbohydrate rich diet (> 150 g/day) for at least three days before the test, followed by an overnight fast. Participants will be instructed to have comparable macronutrient composition of the dinner before the respective study days in the metabolic unit. During the oGTT both capillary and venous blood samples will be collected after 0, 15, 30, 60, 90 and 120 min. To minimize the inconvenience of repeated blood tests during the oGTT, a venous cannula will be inserted, under sterile conditions, prior to the test, for blood sampling. | Week 0 and Week 8 (first intervention); Week 14 and Week 22 (second intervention) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Finger-fold Capillary Density by Capillaroscopy | After 20 min seated at rest, measurements are made with the subject seated and the left hand at heart level. Nail-fold capillaries in the dorsal skin of the third finger are visualized using a stereo microscope linked to a monochrome digital camera. Capillary density is defined as the number of capillaries per mm2 of nail-fold skin and is computed as the mean of 4 measurements. | Week 0 and Week 8 (first intervention); Week 14 and Week 22 (second intervention) | 
| Flow-mediated Dilatation (FMD) | Brachial artery FMD will be assessed. Ultrasound imaging of the brachial artery will be performed. Percent FMD will be calculated using the averaged minimum mean brachial artery diameter at baseline compared to the largest mean values obtained after either release of the forearm occlusion. | Week 0 and Week 8 (first intervention); Week 14 and Week 22 (second intervention) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Oral glucose tolerance test, Flow mediated dilatation, Aortal pulse wave velocity, Finger-fold capillary density by capillaroscopy