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

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

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.

Study Overview

• Status: Completed
• Conditions: Endothelial Dysfunction; Hyperhomocysteinemia; Hypertension Grade I, Subgroup "Borderline" (WHO)
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Verum

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Esslingen, Germany, 73728
    • Biotesys

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Verum; 2 times 2 tablets a day for 4 weeks.	Dietary supplement: Verum; 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.
Placebo Comparator: Placebo; 2 times 2 tablets a day which cornstarch. Tablets look identical like verum tablets.	Dietary supplement: Placebo; corn starch

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Prothrombin Time Between the Visit at Start of Supplementation Phase and the Visit on the Final Day of the 4 Week Supplementation Phase	Prothrombin Time was assessed at the visit at start of the supplementation phase and the visit at the end of the 4 week supplementation phase. Blood coagulability is expressed in units of Quick value. In this case, the measured prothrombin time is expressed in relation to the coagulation time of a healthy person. The value obtained is the "percentage of the standard Quick value". In a person not receiving oral anticoagulation the "normal" Quick value is between 70 and 100%. The longer the patient's coagulation time, the lower the Quick value	Intervention period of 4 weeks

Collaborators and Investigators

• Sponsor: Dr. Loges & Co. GmbH
• Collaborators: BioTeSys GmbH
• Investigators: Study Chair: Birgit Goyvaerts, Dr., Medical Advisor

Publications and helpful links

General Publications

• Reule CA, Goyvaerts B, Schoen C. Effects of an L-arginine-based multi ingredient product on endothelial function in subjects with mild to moderate hypertension and hyperhomocysteinemia - a randomized, double-blind, placebo-controlled, cross-over trial. BMC Complement Altern Med. 2017 Feb 2;17(1):92. doi: 10.1186/s12906-017-1603-9.

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: November 14, 2014
• First Submitted That Met QC Criteria: March 18, 2015
• First Posted (Estimate): March 19, 2015

Study Record Updates

• Last Update Posted (Estimate): May 2, 2016
• Last Update Submitted That Met QC Criteria: March 29, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: hypertension; endothelial function; L-Arginine; vitamin K2; Pycnogenol; vitamin B; Homocystein >10
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Nutrition Disorders; Genetic Diseases, Inborn; Avitaminosis; Deficiency Diseases; Malnutrition; Metabolism, Inborn Errors; Malabsorption Syndromes; Amino Acid Metabolism, Inborn Errors; Vitamin B Deficiency; Hypertension; Hyperhomocysteinemia
• Other Study ID Numbers: BTS815/14

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: Undecided