Type 2 DiabetesPYRAMIDNCT06376240
The Effect of Pyridoxamine Supplementation on Microvascular Function in Type 2 Diabetes
A study testing Pyridoxamine 300mg per day in people with Type 2 Diabetes and Microvascular Function, run by Maastricht University Medical Center at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Type 2 Diabetes, Microvascular Function, Retinopathy, Diabetic
- What is being tested?
- Pyridoxamine 300mg per day
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteNetherlands
- Study dates
- 21 Mar 2024to 13 Mar 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of type 2 diabetes,
- Generalized microvascular dysfunction, i.e.
- eGFR 30-60 mL/min/1.73m2, and/or
- Microalbuminuria albumin-creatinine ratio 3-30 mg/mmol, and/or
- Retinopathy (not proliferative), and/or
- Neuropathy (any).
Who cannot join
- Uncontrolled diabetes (i.e., hypoglycaemia >2 times/week and/or unstable HbA1c >9%),
- Use of >12 Units long-acting insulin per day,
- Use of short-acting insulin,
- Intraocular pressure ≥30 mmHg,
- History of glaucoma,
- Diagnosis of proliferative diabetic retinopathy,
Show all 23Show fewer
- Diagnosis of diabetic macula edema,
- Albumine-creatinine ratio >30 mg/mmol,
- eGFR <30 mL/min/1.73m2,
- Diagnosis of epilepsy,
- Active cardiovascular disease,
- Alcohol usage >4 U/day,
- Drugs abuse,
- Use of systemic glucocorticosteroids,
- Higher grade hypertension
- Diagnosis of inflammatory disease,
- Use of an investigational product within the previous month,
- Unstable body weight,
- Pregnancy or lactation,
- Change in use of oral contraceptives or IUD,
- Unwillingness to give up being a blood donor (or having donated blood) from 8 weeks prior to the start of the study to end of study,
- Insufficient knowledge of the Dutch language,
- Inability to provide written informed consent.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Pyridoxamine Supplementation on Microvascular Function in Type 2 Diabetes: a Double-blind Randomized Placebo-controlled Crossover Trial
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.
Read the detailed description
Rationale:
People with diabetes have an increased risk of malfunctioning of the small blood vessels, e.g. 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 rate/ECG 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, i.e. an estimated glomerular filtration rate (eGFR) of 30-60 mL/min/1.73m2, and/or microalbuminuria of (albumin-creatinine ratio) 3-30 mg/mmol, and/or retinopathy (not proliferative), and/or 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.
- Conditions
- Type 2 Diabetes, Microvascular Function, Retinopathy, Diabetic, Nephropathy, Diabetic, Neuropathy, Diabetic
- Being tested
- Pyridoxamine 300mg per day, Placebo 300mg placebo per day
- Keywords
- Pyridoxamine, Advanced Glycation End Products, Methylglyoxal, Type 2 Diabetes
- Medical subject headings
- Diabetes Mellitus, Type 2, Diabetic Retinopathy, Diabetic Nephropathies, Diabetic Neuropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pyridoxamine 300mg per dayDietary supplement
oral supplement
Placebo 300mg placebo per dayOther
oral supplement
| Study group | Role | What they receive |
|---|---|---|
| Treatment order AB | Experimental | Treatment with A (either pyridoxamine or placebo) in period 1 followed by treatment with B (either pyridoxamine or placebo) in period 2. Receives: Dietary Supplement: Pyridoxamine 300mg per day; Other: Placebo 300mg placebo per day |
| Treatment order BA | Experimental | Treatment with B (either pyridoxamine or placebo) in period 1 followed by treatment with A (either pyridoxamine or placebo) in period 2. Receives: Dietary Supplement: Pyridoxamine 300mg per day; Other: Placebo 300mg placebo per day |
What is being measured
The primary outcome is the main question the study is designed to answer.
Central retinal artery equivalent of the eye
in μm, measured with funduscopy
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2024
- Study start21 Mar 2024
- Primary completion13 Mar 2026
- Study completion13 Mar 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- More trials run by Maastricht University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Diabetes Fonds
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06376240
- Sponsor's protocol ID
- NL85203.068.23
- Acronym
- PYRAMID
- Status last verified
- Apr 2026
- First submitted
- 8 Apr 2024
- Last updated
- 27 Apr 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Pyridoxamine Supplementation on Microvascular Function in Type 2 Diabetes: a Double-blind Randomized Placebo-controlled Crossover Trial
- ClinicalTrials.gov ID
- NCT06376240
- Acronym / sponsor ID
- PYRAMID / NL85203.068.23
- Conditions
- Type 2 Diabetes, Microvascular Function, Retinopathy, Diabetic, Nephropathy, Diabetic, Neuropathy, Diabetic
- Keywords
- Pyridoxamine, Advanced Glycation End Products, Methylglyoxal, Type 2 Diabetes
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Collaborators
- Diabetes Fonds
- Study start
- 21 Mar 2024 (actual)
- Primary completion
- 13 Mar 2026 (actual)
- Study completion
- 13 Mar 2026 (actual)
- First posted
- 19 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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, e.g. 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 rate/ECG 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, i.e. an estimated glomerular filtration rate (eGFR) of 30-60 mL/min/1.73m2, and/or microalbuminuria of (albumin-creatinine ratio) 3-30 mg/mmol, and/or retinopathy (not proliferative), and/or 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment order AB | Experimental | Dietary Supplement: Pyridoxamine 300mg per day, Other: Placebo 300mg placebo per dayTreatment with A (either pyridoxamine or placebo) in period 1 followed by treatment with B (either pyridoxamine or placebo) in period 2. |
| Treatment order BA | Experimental | Dietary Supplement: Pyridoxamine 300mg per day, Other: Placebo 300mg placebo per dayTreatment with B (either pyridoxamine or placebo) in period 1 followed by treatment with A (either pyridoxamine or placebo) in period 2. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Diagnosis of type 2 diabetes,
- Generalized microvascular dysfunction, i.e.
Key exclusion criteria (23 listed)
- Uncontrolled diabetes (i.e., hypoglycaemia >2 times/week and/or unstable HbA1c >9%),
- Use of >12 Units long-acting insulin per day,
- Use of short-acting insulin,
- Intraocular pressure ≥30 mmHg,
- History of glaucoma,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pyridoxamine 300mg per dayoral supplement | Dietary supplement | Treatment order AB, Treatment order BA |
| Placebo 300mg placebo per dayoral supplement | Other | Treatment order AB, Treatment order BA |
Primary outcome
Central retinal artery equivalent of the eye
Time frame: 8 weeks
in μm, measured with funduscopy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Pyridoxamine 300mg per day in people with Type 2 Diabetes and Microvascular Function, run by Maastricht University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Central retinal artery equivalent of the eye (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2026.