Effect of L-Arginine and Pycnogenol on Light to Moderate Hypertension and Endothelial Function

Study Overview
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Brief Summary
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The effect of a combination product (Verum ) with L-arginine, Pycnogenol, vitamin K2, R-(+)-alpha-lipoic acid and vitamins B6, B12 and folic acid is investigated in a double blind placebo-controlled cross-over study. Volunteers with hypertension and hyperhomocysteinemia are randomly assigned to the dietary supplement or placebo.

Detailed Description
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25 patients were included in the trial. Intervention period was 4 weeks with 2 months wash out phase. The screening visit of all volunteers before study start included volunteer information, signature of informed consent, anamnesis, medical history, ECG and blood routine analysis. Efficacy parameters were measured at visit 1, 2, 3, and 4. Endothelial function and postprandial endothelial Reaction was tested using EndoPAT (validated diagnosis tool). Blood pressure was measured by volunteers over a period of 7 days before each visit. As additional parameters homocysteine and ADMA (assymmetric dimethyl arginine) were determed. For safety evaluation AEs (Adverse Events), CC (compliance control), tolerability, blood routine parameters and vital signs were assessed.

Official Title
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Effect of a Dietary Supplement on Endothelial Function in Volunteers With Light to Moderate Hypertension - a Randomised, Double-blind, Placebo Controlled Cross-over Study

Conditions
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Endothelial Dysfunction, Hyperhomocysteinemia, Hypertension Grade I, Subgroup Borderline (WHO)

Intervention / Treatment
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* Dietary Supplement: Verum
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: borderline blood pressure (systolic 130-149) homocystein level >10µmol/l Exclusion Criteria: e.g. BMI <20kg/m2 and >32kg/m2 use of antihypertensives, anticoagulants, and statins cardiovascular diseases e.g. stroke, myocardial infarction use of L-arginine and other dietary supplements

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Verum<br>2 times 2 tablets a day for 4 weeks. | Dietary Supplement: Verum<br>* 2400 mg L-arginine, 80 mg Pycnogenol, 45µg vitamine K2, 10 mg R (+) alpha lipoic acid, 8 mg vitamine B6, 500 µg vitamine B12, and 600 mg folic acid.<br>|
| Placebo Comparator: Placebo<br>2 times 2 tablets a day which cornstarch. Tablets look identical like verum tablets. | Dietary Supplement: Placebo<br>* corn starch<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Endothelial Function Between the Visit at Start of Supplementation Phase and the Visit on the Final Day of the 4 Week Supplementation Phase (Delta lnRHI) | Endothelial function was determined with the EndoPAT™ method (non-invasive Peripheral Aterial Tonometry) using a reactive hyperemia procedure. The outcome measure is the change in endothelial function between the visit at start of the supplementation phase and the visit on the final day of the 4 week supplementation phase. The endothelial function is determined as the natural log of the Reactive Hyperemia Index (lnRHI) which is the post-to-pre occlusion peripheral arterial tonometry signal ratio in the occluded side, relative to the same ratio in the control side, corrected for baseline vascular tone of the occluded side. Normal lnRHI > 0.51, Abnormal lnRHI < 0.51 | Intervention period of 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean of Blood Pressure Measured Daily at the Last 7 Days of the 4 Week Intervention Period. | The mean of daily systolic and diastolic blood pressure measured daily at the last 7 days of the 4 week intervention period. Measurements were performed by subjects at home and were taken on the left arm, after at least 10 minutes of rest, in a sitting position. | Intervention period of 4 weeks | 
| Homocystein Level Determined on the Final Day of the 4 Week Intervention Period. | Homocystein level in µmol/l was determined on the final day of the 4 week intervention period. The first supplementation period started at visit one and lasted for 4 weeks. It was followed by a wash out phase of 8 weeks and subsequently by a second supplementation phase of 4 weeks (cross-over design) | After intervention period of 4 weeks | 
| Asymmetric Dimethyl Arginine (ADMA) Level Determined on the Final Day of the 4 Week Intervention Period. | ADMA (asymmetric dimethyl arginine) was determined on the final day of the 4 week intervention period. Samples were analyzed batch wise using an enzymatic test | After intervention period of 4 weeks | 
| Glycated Hemoglobin (HbA1c) Determined on the Final Day of the 4 Week Intervention Period. | Glycated hemoglobin (HbA1c) as percentage of total hemoglobin was determined on the final day of the 4 week intervention period. | After intervention period of 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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L-Arginine, Pycnogenol, vitamin K2, vitamin B, endothelial function, hypertension, Homocystein >10