Effect of Pyridoxamine Supplementation on Vascular Function and Insulin Sensitivity

Study Overview
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Brief Summary
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A growing body of evidence demonstrates that increased adipose mass, especially visceral adipose tissue, contributes directly towards an increase in systemic inflammation, (micro-)vascular dysfunction and the burden of cardiovascular disease (CVD), insulin resistance and type 2 diabetes. Advanced glycation/lipoxidation endproducts (AGEs/ALEs) are a heterogeneous family of unavoidable by-products, which are formed by reactive metabolic intermediates derived from glucose and lipid oxidation. In addition to the overwhelming amount of data demonstrating the role of AGEs/ALEs in the development of (micro-)vascular dysfunction and disease, accumulation of AGEs/ALEs in the expanding adipose tissue contributes to the dysregulation of adipokines and the development of insulin resistance. The investigators want to examine, in a double-blind randomized placebo controlled parallel study, the physiological effect of a dietary intervention with pyridoxamine in abdominally obese persons. A sub-study is implemented next to the clinical trial. The objective of the sub-study is to measure the metabolization and kinetics of pyridoxamine in plasma and urine with UPLC-MS/MS. The sub-study comprises of 5 additional healthy volunteers, with pyridoxamine as an oral supplement.

Official Title
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The Effect of Pyridoxamine Supplementation on Vascular Function and Insulin Sensitivity; a Double-blind Randomized Placebo Controlled Trial in Abdominally Obese Subjects.

Conditions
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Abdominal Obesity Metabolic Syndrome

Intervention / Treatment
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* Dietary Supplement: Pyridoxamine
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Abdominal obesity: Waist circumference for men should be above 102 cm and for women above 88 cm. Caucasian (because of skin fluorescence and capillary microscopy measurements) Aged 18-75 years Exclusion Criteria: Diabetes (i.e. using anti-diabetic medication, fasting glucose >7.0 mmol/L, HbA1c >6.5%). Active or history of cardiovascular disease (e.g. stroke, coronary artery disease, peripheral vascular disease, congestive heart failure, cardiac shunts, cardiac surgery, pulmonary hypertension, cardiac arrhythmias, family history of cardiac arrhythmias or sudden cardiac death) Hyperlipidemia (defined as serum total cholesterol > 8 mmol/L or TG > 4 mmol/L) Smoking (>10 cigarettes per day) High alcohol usage (>4 U/day) or drug abuse Use of medication known to influence glucose metabolism, vascular function (e.g. glucocorticosteroids, NSAID's) Higher grade hypertension (> 179 mmHg SBP and/or > 109 mmHg DBP) in order not to expose subjects to unnecessary risks) Known allergic reaction to ultrasound contrast-agent Pulmonary or inflammatory disease Kidney failure or electrolyte disorders Use of dietary supplements or an investigational product within the previous month Unstable body weight (no drastic changes in life style before or during the intervention are allowed, this means no weight gain or loss >3 kg in the last two months) Pregnancy or lactation No change in use of oral anticonceptiva or IUD (12 weeks prior of during the intervention) Unwillingness to give up being a blood donor (or having donated blood) from 8 weeks prior to the start of the study and during the study Insufficient knowledge of the Dutch language

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pyridoxamine (1)<br>Subjects will be asked to consume dietary supplements containing pyridoxamine (dosage 1), three times daily during 8 weeks. | Dietary Supplement: Pyridoxamine<br> <br> |
| Active Comparator: Pyridoxamine (2)<br>Subjects will be asked to consume dietary supplements containing pyridoxamine (dosage 2), three times daily during 8 weeks | Dietary Supplement: Pyridoxamine<br> <br> |
| Placebo Comparator: Placebo<br>Subjects will be asked to consume dietary supplements containing placebo (amylum solani), three times daily during 8 weeks | Dietary Supplement: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin sensitivity | Assessed by hyperinsulinemic-euglycemic clamp | Difference after 8 weeks of intervention | 
| Microvascular function | Assessed by contrast-enhanced ultrasound (CEUS) in skeletal muscle | Difference after 8 weeks of intervention |