Effect of Pyridoxamine Supplementation on Vascular Function and Insulin Sensitivity

• Sponsor: Maastricht University Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02954588
• Collaborator: Top Institute Food and Nutrition (Other), Center for Translational Molecular Medicine (Other)
• Enrollment: 112
• Location: 1
• Arms: 3
• Actual Duration (Months): 45.8
• Patients Per Site Per Month: 2.4

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Abdominal Obesity Metabolic Syndrome	Dietary Supplement: Pyridoxamine; Dietary Supplement: Placebo	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 112 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: The Effect of Pyridoxamine Supplementation on Vascular Function and Insulin Sensitivity; a Double-blind Randomized Placebo Controlled Trial in Abdominally Obese Subjects.
• Actual Study Start Date: Oct 14, 2016
• Actual Primary Completion Date: Jan 20, 2020
• Actual Study Completion Date: Aug 8, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Insulin sensitivity [Difference after 8 weeks of intervention]

   Assessed by hyperinsulinemic-euglycemic clamp

2. Microvascular function [Difference after 8 weeks of intervention]

   Assessed by contrast-enhanced ultrasound (CEUS) in skeletal muscle

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Maastricht University Medical Center	Maastricht		Netherlands	6200MD

Sponsors and Collaborators

• Maastricht University Medical Center
• Top Institute Food and Nutrition
• Center for Translational Molecular Medicine

Investigators

• Principal Investigator: Casper G Schalkwijk, PhD, Maastricht University Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Maastricht University Medical Center
• ClinicalTrials.gov Identifier: NCT02954588
• Other Study ID Numbers: NL51023.068.16
• First Posted: Nov 3, 2016
• Last Update Posted: Oct 1, 2020
• Last Verified: Sep 1, 2020

• Additional relevant MeSH terms: Metabolic Syndrome; Insulin Resistance; Obesity, Abdominal; Pyridoxamine

Study Results

No Results Posted as of Oct 1, 2020