Endothelial Dysfunction, Hyperhomocysteinemia, Hypertension Grade I, Subgroup Borderline (WHO)
Conditions
Keywords
L-Arginine, Pycnogenol, vitamin K2, vitamin B, endothelial function, hypertension, Homocystein >10
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.
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.
Interventions
DIETARY_SUPPLEMENTVerum
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.
DIETARY_SUPPLEMENTPlacebo
corn starch
Sponsors
BioTeSys GmbH
Dr. Loges & Co. GmbH
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | 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
| Measure | Time frame | Description |
|---|---|---|
| Mean of Blood Pressure Measured Daily at the Last 7 Days of the 4 Week Intervention Period. | 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. |
| Homocystein Level Determined on the Final Day of the 4 Week Intervention Period. | 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) |
| Asymmetric Dimethyl Arginine (ADMA) Level Determined on the Final Day of the 4 Week Intervention Period. | 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 |
| Glycated Hemoglobin (HbA1c) Determined on the Final Day of the 4 Week Intervention Period. | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 |
Countries
Germany
Participant flow
Recruitment details
Cross-over study
Participants by arm
| Arm | Count |
|---|---|
| First Verum, Then Placebo 2 times a day 2 verum tablets for 4 weeks. 8 weeks wash out. Then 2 times a day 2 placebo tablets for 4 weeks. | 12 |
| First Placebo, Then Verum 2 times a day 2 placebo tablets for 4 weeks. 8 weeks wash out. Then 2 times a day 2 verum tablets for 4 weeks. | 13 |
| Total | 25 |
Baseline characteristics
| Characteristic | First Verum, Then Placebo | First Placebo, Then Verum | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 13 Participants | 25 Participants |
| Region of Enrollment Germany | 12 participants | 13 participants | 25 participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Male | 9 Participants | 9 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 25 | 12 / 25 |
| serious Total, serious adverse events | 0 / 25 | 0 / 25 |
Outcome results
Primary
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
Time frame: Intervention period of 4 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Verum | 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) | 0.070 Delta lnRHI [Index] |
| Placebo | 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) | -0.052 Delta lnRHI [Index] |
Secondary
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
Time frame: After intervention period of 4 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Verum | Asymmetric Dimethyl Arginine (ADMA) Level Determined on the Final Day of the 4 Week Intervention Period. | 0.638 µmol/l |
| Placebo | Asymmetric Dimethyl Arginine (ADMA) Level Determined on the Final Day of the 4 Week Intervention Period. | 0.632 µmol/l |
Secondary
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.
Time frame: After intervention period of 4 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Verum | Glycated Hemoglobin (HbA1c) Determined on the Final Day of the 4 Week Intervention Period. | 5.37 percentage of total hemoglobin |
| Placebo | Glycated Hemoglobin (HbA1c) Determined on the Final Day of the 4 Week Intervention Period. | 5.34 percentage of total hemoglobin |
Secondary
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)
Time frame: After intervention period of 4 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Verum | Homocystein Level Determined on the Final Day of the 4 Week Intervention Period. | 9.10 μmol/l |
| Placebo | Homocystein Level Determined on the Final Day of the 4 Week Intervention Period. | 11.95 μmol/l |
Secondary
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.
Time frame: Intervention period of 4 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Verum | Mean of Blood Pressure Measured Daily at the Last 7 Days of the 4 Week Intervention Period. | systolic reading | 132.8 mmHg |
| Verum | Mean of Blood Pressure Measured Daily at the Last 7 Days of the 4 Week Intervention Period. | diastolic reading | 82.2 mmHg |
| Placebo | Mean of Blood Pressure Measured Daily at the Last 7 Days of the 4 Week Intervention Period. | systolic reading | 133.2 mmHg |
| Placebo | Mean of Blood Pressure Measured Daily at the Last 7 Days of the 4 Week Intervention Period. | diastolic reading | 83.5 mmHg |
Other Pre-specified
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
Time frame: Intervention period of 4 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Verum | 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 | 2.00 Percentage of the standard Quick value |
| Placebo | 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 | 1.50 Percentage of the standard Quick value |