Effect of Pyridoxamine Supplementation on Vascular Function and Insulin Sensitivity

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

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.

Study Overview

• Status: Completed
• Conditions: Abdominal Obesity Metabolic Syndrome
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Pyridoxamine

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Maastricht, Netherlands, 6200MD
    • Maastricht University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Collaborators: Center for Translational Molecular Medicine; Top Institute Food and Nutrition
• Investigators: Principal Investigator: Casper G Schalkwijk, PhD, Maastricht University Medical Center

Publications and helpful links

General Publications

• Van den Eynde MDG, Scheijen JLJM, Stehouwer CDA, Miyata T, Schalkwijk CG. Quantification of the B6 vitamers in human plasma and urine in a study with pyridoxamine as an oral supplement; pyridoxamine as an alternative for pyridoxine. Clin Nutr. 2021 Jul;40(7):4624-4632. doi: 10.1016/j.clnu.2021.05.028. Epub 2021 Jun 10.

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2016
• Primary Completion (Actual): January 20, 2020
• Study Completion (Actual): August 8, 2020

Study Registration Dates

• First Submitted: November 2, 2016
• First Submitted That Met QC Criteria: November 2, 2016
• First Posted (Estimate): November 3, 2016

Study Record Updates

• Last Update Posted (Actual): October 1, 2020
• Last Update Submitted That Met QC Criteria: September 29, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Overnutrition; Nutrition Disorders; Hyperinsulinism; Obesity; Metabolic Syndrome; Insulin Resistance; Obesity, Abdominal; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Pyridoxamine
• Other Study ID Numbers: NL51023.068.16