A Study to Assess the Effect of a 3-month Folate Supplementation on Systemic Homocysteine Plasma Concentration and Ocular Blood Flow in Patients With Diabetes

Study Overview
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Brief Summary
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There is evidence that a folate deficiency - and as the biological consequence of the latter - higher homocysteine plasma levels are associated with an increased risk of vascular associated diseases. For the eye, it has been shown that higher intake of folate reduces the risk of vascular related diseases such as age related macular degeneration. Further studies suggest that decreased serum levels of folate and vitamin B12 may be an independent risk factor for diabetic retinopathy. The reason for the association of low folate levels and the increased risk for vascular-associated ocular diseases is not entirely clear but may be at least partially related to an impairment of local blood flow regulation in these patients. Whether supplementation with folate may improve vascular regulation has not yet been sufficiently investigated. However, given that the potential effect size of a folate substitution on blood flow and systemic blood parameters is unclear, a proper statistical design for a large, controlled, randomized study is difficult. Thus, the present pilot study should (1) provide information about the homocysteine lowering potential of the formulation under study and (2) identify potential vascular related outcome parameters for further, larger, placebo-controlled studies and provide sufficient data to allow for a proper statistical planning for such a study. Consequently, the current study seeks to investigate the effect of a 3-month supplementation with folate on systemic homocysteine plasma levels. Further, ocular blood flow and endothelial function in the ocular microcirculation will be assessed. For this purpose, a group of 25 patients with diabetes mellitus will be included in the study. Outcome parameters will be assessed at baseline and after a 3-month supplementation with folate.

Official Title
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A Pilot Study to Assess the Effect of a 3-month Folate Supplementation on Systemic Homocysteine Plasma Concentration and Ocular Blood Flow in Patients With Diabetes

Conditions
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Diabetes

Intervention / Treatment
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* Dietary Supplement: Ocufolin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Diabetes mellitus type 1 or 2 No or mild non-proliferative diabetic retinopathy Normal findings in the medical history except diabetes unless the investigator considers an abnormality to be clinically irrelevant Normal ophthalmic findings except mild non-proliferative retinopathy Ametropy ≤ 6 diopters Exclusion Criteria: Participation in a clinical trial in the 3 weeks preceding the screening visit Symptoms of a clinically relevant illness in the 3 weeks before the first study day Presence or history of a severe medical condition relevant to the study, except diabetes, as judged by the clinical investigator Intake of dietary supplements containing folate within the three months before the screening visit Untreated or uncontrolled arterial hypertension (defined as either systolic blood pressure >150 mmHg or diastolic blood pressure >95 mmHg) Blood donation during the previous three weeks Moderate to severe non-proliferative or proliferative diabetic retinopathy Previous laser photocoagulation treatment History or family history of epilepsy Presence of any abnormalities preventing reliable measurements in the study eye as judged by the investigator Best corrected visual acuity < 0.8 Snellen Ametropy > 6 Dpt Pregnancy, planned pregnancy or lactating

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with Diabetes<br>Patients with Type 1 or Type 2 Diabetes | Dietary Supplement: Ocufolin<br>* Ocufolin, Aprofol AG, Switzerland Dose: 1 capsule per day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma homocysteine level | Laboratory analysis for plasma homocysteine level in µmol/L | Change from Baseline plasma homocysteine level at 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Retinal blood flow | Retinal blood flow will be assessed using Fourier domain optical coherence tomography, providing values in µl/min | Change from Baseline retinal blood flow at 3 months | 
| Retinal vessel diameters |  | Change from Baseline retinal vessel diameters at 3 months |