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

• ClinicalTrials.gov Identifier: NCT02392767
• Recruitment Status: Completed
• First Posted: March 19, 2015
• Results First Posted: May 2, 2016
• Last Update Posted: May 2, 2016
• Sponsor: Dr. Loges & Co. GmbH
• Collaborator: BioTeSys GmbH
• Information provided by (Responsible Party): Dr. Loges & Co. GmbH

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Endothelial Dysfunction; Hyperhomocysteinemia; Hypertension Grade I, Subgroup "Borderline" (WHO)	Dietary Supplement: Verum; Dietary Supplement: Placebo	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 25 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Effect of a Dietary Supplement on Endothelial Function in Volunteers With Light to Moderate Hypertension - a Randomised, Double-blind, Placebo Controlled Cross-over Study
• Study Start Date: October 2014
• Actual Primary Completion Date: August 2015
• Actual Study Completion Date: August 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. 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") [ Time Frame: Intervention period of 4 weeks ]

   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

Secondary Outcome Measures :

1. Mean of Blood Pressure Measured Daily at the Last 7 Days of the 4 Week Intervention Period. [ Time Frame: Intervention period of 4 weeks ]
   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.
2. Homocystein Level Determined on the Final Day of the 4 Week Intervention Period. [ Time Frame: After intervention period of 4 weeks ]

   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)

3. Asymmetric Dimethyl Arginine (ADMA) Level Determined on the Final Day of the 4 Week Intervention Period. [ Time Frame: After intervention period of 4 weeks ]
   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
4. Glycated Hemoglobin (HbA1c) Determined on the Final Day of the 4 Week Intervention Period. [ Time Frame: After intervention period of 4 weeks ]
   Glycated hemoglobin (HbA1c) as percentage of total hemoglobin was determined on the final day of the 4 week intervention period.

Other Outcome Measures:

1. 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 [ Time Frame: Intervention period of 4 weeks ]
   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

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

Germany

BioTeSys

Esslingen, Germany, 73728

Sponsors and Collaborators

Dr. Loges & Co. GmbH

BioTeSys GmbH

Investigators

• Study Chair: Birgit Goyvaerts, Dr.; medical advisor

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Dr. Loges & Co. GmbH
• ClinicalTrials.gov Identifier: NCT02392767
• Other Study ID Numbers: BTS815/14
• First Posted: March 19, 2015
• Results First Posted: May 2, 2016
• Last Update Posted: May 2, 2016
• Last Verified: March 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided
• Plan Description: Undecided

Keywords provided by Dr. Loges & Co. GmbH:

L-Arginine; Pycnogenol; vitamin K2; vitamin B; endothelial function; hypertension; Homocystein >10

Additional relevant MeSH terms:

Hypertension; Hyperhomocysteinemia; Vascular Diseases; Cardiovascular Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Malabsorption Syndromes; Metabolic Diseases; Vitamin B Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders