Ignite Creation Date:
2024-05-06 @ 8:25 PM
Last Modification Date:
2024-10-26 @ 3:27 PM
Study NCT ID:
NCT06376240
Status:
RECRUITING
Last Update Posted:
2024-04-19
First Post:
2024-04-08
Brief Title:
The Effect of Pyridoxamine Supplementation on Microvascular Function in Type 2 Diabetes
Sponsor:
Maastricht University Medical Center
Organization:
Maastricht University Medical Center
Study Overview
Official Title:
The Effect of Pyridoxamine Supplementation on Microvascular Function in Type 2 Diabetes a Double-blind Randomized Placebo-controlled Crossover Trial
Status:
RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PYRAMID
Brief Summary:
Patients with type 2 diabetes have an increased risk of developing vascular complications Microvascular dysfunction might be caused by the increased production of methylglyoxal under hyperglycaemic conditions Methylglyoxal is a by-product of glycolysis and forms advanced glycation endproducts AGEs on proteins and DNA thereby disrupting their function Preventing methylglyoxal accumulation and AGEs formation may offer a therapeutic option for treating microvascular complications in diabetics Pyridoxamine is a vitamin B6 vitamer that scavenges methylglyoxal and thereby inhibits the formation of AGEs In this study the researchers investigate whether pyridoxamine supplementation in type 2 diabetes improves microvascular function in the eye kidney and skin and reduces markers of endothelial dysfunction and glycation
Detailed Description:
Rationale
People with diabetes have an increased risk of malfunctioning of the small blood vessels eg in the eye and kidney which can lead to blindness and kidney failure These are serious complications but to date there are no options to improve specifically the function of the small blood vessels But why do people with diabetes have such an increased risk of dysfunction of the small blood vessels The investigators have shown that a high glucose concentration in the blood plays an important role in the dysfunction of particularly the small blood vessels A possible explanation for this dysfunction is an increased production of methylglyoxal which arises from the breakdown of glucose Methylglyoxal is a small but highly reactive molecule that can damage various organs and tissues In several studies the investigators found that methylglyoxal is increased in type 1 and type 2 diabetes and that methylglyoxal is associated with dysfunction of the smaller blood vessels In our previous research in small laboratory animals The investigators have shown that methylglyoxal directly causes damage of the small blood vessels Because of these potentially harmful effects of methylglyoxal the investigators have tried to reduce circulating methylglyoxal In small laboratory animals the investigators have found that the vitamin B6 isoform pyridoxamine inhibits the formation and accumulation of methylglyoxal and improves vascular function In a clinical trial in people with overweight the investigators found that supplementation of pyridoxamine is safe and that methylglyoxal levels can be reduced and the investigators found indications of an improvement of vascular function
Objective
Primary objective to study whether pyridoxamine supplementation in type 2 diabetes improves microvascular function in the eye kidney and skin and reduces markers of endothelial dysfunction and glycation
Secondary objective to study whether pyridoxamine supplementation in type 2 diabetes improves glucose metabolism advanced glycation endproduct AGE concentrations in blood plasma and skin methylglyoxal glyoxal and 3-deoxyglucose concentrations in blood plasma adipokines and inflammatory markers in blood plasma markers of dicarbonyl stress and oxidative stress in urine liver fat blood pressure heart rateECG and body composition
Study design
The study will be conducted in a randomized double blind placebo-controlled manner This intervention study includes two intervention periods of 8 weeks in a crossover design with a washout period of 4 weeks
Study population
Adult individuals 18 years old with type 2 diabetes and with generalized microvascular dysfunction ie an estimated glomerular filtration rate eGFR of 30-60 mLmin173m2 andor microalbuminuria of albumin-creatinine ratio 3-30 mgmmol andor retinopathy not proliferative andor neuropathy any
Intervention
The daily dosage 300 mg pyridoxamine or placebo will be supplied as three capsules of 100mg each per day and are taken shortly before or during the meal
Main study parameter
The main study parameter is microvascular function in the eye skin plasma and kidney measured by means of retinal funduscopy adaptive optics funduscopy optical coherence tomography OCT dynamic vessel analyser skin laser doppler flowmetry markers of endothelial function in the blood plasma urinary albumin and estimated glomerular filtration rate
Nature and extent of the burden and risks associated with participation benefit and group relatedness
The number of measurements during each visit in this study is quite substantial Nonetheless the investigators expect that the burden for the subjects is limited since all measurements except blood withdrawal are non-invasive and are performed while sitting or in a supine relaxed and comfortable position Additionally potential benefits of participating in this study are directly related to the possible beneficiary effects of pyridoxamine as showed in a previous clinical trial Moreover pyridoxamine supplementation in this previous clinical trial did not result in serious adverse effects
People with diabetes have an increased risk of malfunctioning of the small blood vessels eg in the eye and kidney which can lead to blindness and kidney failure These are serious complications but to date there are no options to improve specifically the function of the small blood vessels But why do people with diabetes have such an increased risk of dysfunction of the small blood vessels The investigators have shown that a high glucose concentration in the blood plays an important role in the dysfunction of particularly the small blood vessels A possible explanation for this dysfunction is an increased production of methylglyoxal which arises from the breakdown of glucose Methylglyoxal is a small but highly reactive molecule that can damage various organs and tissues In several studies the investigators found that methylglyoxal is increased in type 1 and type 2 diabetes and that methylglyoxal is associated with dysfunction of the smaller blood vessels In our previous research in small laboratory animals The investigators have shown that methylglyoxal directly causes damage of the small blood vessels Because of these potentially harmful effects of methylglyoxal the investigators have tried to reduce circulating methylglyoxal In small laboratory animals the investigators have found that the vitamin B6 isoform pyridoxamine inhibits the formation and accumulation of methylglyoxal and improves vascular function In a clinical trial in people with overweight the investigators found that supplementation of pyridoxamine is safe and that methylglyoxal levels can be reduced and the investigators found indications of an improvement of vascular function
Objective
Primary objective to study whether pyridoxamine supplementation in type 2 diabetes improves microvascular function in the eye kidney and skin and reduces markers of endothelial dysfunction and glycation
Secondary objective to study whether pyridoxamine supplementation in type 2 diabetes improves glucose metabolism advanced glycation endproduct AGE concentrations in blood plasma and skin methylglyoxal glyoxal and 3-deoxyglucose concentrations in blood plasma adipokines and inflammatory markers in blood plasma markers of dicarbonyl stress and oxidative stress in urine liver fat blood pressure heart rateECG and body composition
Study design
The study will be conducted in a randomized double blind placebo-controlled manner This intervention study includes two intervention periods of 8 weeks in a crossover design with a washout period of 4 weeks
Study population
Adult individuals 18 years old with type 2 diabetes and with generalized microvascular dysfunction ie an estimated glomerular filtration rate eGFR of 30-60 mLmin173m2 andor microalbuminuria of albumin-creatinine ratio 3-30 mgmmol andor retinopathy not proliferative andor neuropathy any
Intervention
The daily dosage 300 mg pyridoxamine or placebo will be supplied as three capsules of 100mg each per day and are taken shortly before or during the meal
Main study parameter
The main study parameter is microvascular function in the eye skin plasma and kidney measured by means of retinal funduscopy adaptive optics funduscopy optical coherence tomography OCT dynamic vessel analyser skin laser doppler flowmetry markers of endothelial function in the blood plasma urinary albumin and estimated glomerular filtration rate
Nature and extent of the burden and risks associated with participation benefit and group relatedness
The number of measurements during each visit in this study is quite substantial Nonetheless the investigators expect that the burden for the subjects is limited since all measurements except blood withdrawal are non-invasive and are performed while sitting or in a supine relaxed and comfortable position Additionally potential benefits of participating in this study are directly related to the possible beneficiary effects of pyridoxamine as showed in a previous clinical trial Moreover pyridoxamine supplementation in this previous clinical trial did not result in serious adverse effects
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None