Hypertension
Conditions
Brief summary
The purpose of this study is to investigate the efficacy of Flavangenol® (Toyo Shinyaku, Japan), a pine bark extract, in lowering blood pressure and improving glycemic control and plasma lipoprotein profile.
Detailed description
Cardiovascular disease is the number one cause of death in the Unites States. Our study tests the efficacy of pine bark extract in improving a number of cardiovascular disease risk factors. We are conducting a randomized, placebo-controlled, double-blind, parallel trial that will investigate the efficacy and safety of Flavangenol® (Toyo Shinyaku, Japan), a pine bark extract, among 130 study participants. These participants will be individuals at mildly or moderately elevated risk of cardiovascular disease (CVD) because of having prehypertension, excess body weight, and insulin insensitivity. We aim to determine (in order of priority): 1. The efficacy of Flavangenol in lowering blood pressure. 2. The efficacy of Flavangenol in improving glycemic control and plasma lipoprotein profile. 3. Changes in body weight, antioxidative capacity, anti-inflammatory markers, blood coagulation factors, and liver function tests in response to Flavangenol. 4. The safety of Flavangenol, as confirmation of past studies.
Interventions
DRUGPine Bark Extract (Flavangenol®)
Flavangenol 200 mg per day. Flavangenol is a brand of pine bark extract manufactured by Toyo Shinyaku of Saga, Japan. Dosage delivered as four tablets, each containing 50 mg Flavangenol, all 4 tablets taken once per day orally for 12 weeks.
Sponsors
Funded by Toyo Shinyaku Co Ltd
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Systolic blood pressure between 125 and 159 mmHg and diastolic blood pressure (DBP) \< 100 mmHg * Body mass index (BMI) 25.0-34.9 * Triglycerides (TG) \< 450 mg/dL * Low Density Lipoprotein (LDL) \< 200 mg/dL * Fasting blood glucose (FBG) \< 126 mg/dL
Exclusion criteria
* DBP \> 95 mmHg * LDL \> 170 mg/dL * TG \> 300 mg/dL * FBG \> 110 mg/dL
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Combined Change in Systolic and Diastolic Blood Pressures From Baseline to Week 12. | three months | Mean at Week 12 observation minus mean at Baseline observation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fasting Insulin | three months | Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up). |
| Hemoglobin A1c | three months | Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up). |
| ALT/SGPT | three months | Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up). |
| AST/SGOT | three months | Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up). |
| Total Cholesterol | 3 months | Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up). |
| LDL | 3 months | Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up). |
| HDL | 3 months | Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up). |
| Fasting Blood Glucose | three months | Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up). |
| LDL Particle Size | 3 months | Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up). |
| HDL Particle Size | 3 months | Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up). |
| Lipoprotein A | three months | Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up). Calculated as (Pinebark\_Followup - Pinebark\_Baseline) - (Placebo\_Follow-up - Placebo\_Baseline) |
| C-reactive Protein | three months | Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up). |
| Body Mass Index | three months | Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up). |
| Weight | 3 months | Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up). |
| Triglycerides | three months | Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up). |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the local community through the use of radio and print advertisements between January 31, 2007 and May 31, 2008.
Pre-assignment details
Prior to randomization, participants were scheduled to complete two baseline visits three to seven days apart at the Stanford GCRC. Only those who successfully completed both baseline visits were randomized into the study.
Participants by arm
| Arm | Count |
|---|---|
| Pine Bark Extract 200 mg Flavangenol delivered once per day orally. Flavangenol is a brand of Pine Bark Extract manufactured by Toyo Shinyaku of Saga, Japan. Dosage delivered as four tablets 50 mg each; 4 tablets taken in the morning daily. Pine Bark Extract (Flavangenol�) : Flavangenol 200 mg per day. Dosage delivered as four tablets, 50 mg per tablet, taken once per day orally for 12 weeks. | 64 |
| Placebo Placebo delivered as four tablets matching the active product; four tablets taken daily orally. | 66 |
| Total | 130 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Began cancer treatments | 1 | 0 |
| Overall Study | Began hypertension medication | 1 | 0 |
| Overall Study | Concern about Supplement | 2 | 0 |
| Overall Study | Inconvenience | 0 | 2 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Moved from area | 0 | 1 |
Baseline characteristics
| Characteristic | Pine Bark Extract | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 13 Participants | 11 Participants | 24 Participants |
| Age, Categorical Between 18 and 65 years | 51 Participants | 55 Participants | 106 Participants |
| Age, Continuous | 56.9 years STANDARD_DEVIATION 9.8 | 53.9 years STANDARD_DEVIATION 12 | 55.4 years STANDARD_DEVIATION 11 |
| Sex: Female, Male Female | 25 Participants | 23 Participants | 48 Participants |
| Sex: Female, Male Male | 39 Participants | 43 Participants | 82 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 24 / 64 | 29 / 66 |
| serious Total, serious adverse events | 1 / 64 | 2 / 66 |
Outcome results
Primary
Combined Change in Systolic and Diastolic Blood Pressures From Baseline to Week 12.
Mean at Week 12 observation minus mean at Baseline observation.
Time frame: three months
Population: The data was analyzed on an intent-to-treat basis, with the last observation collected carried forward for participants with missing data at follow-up.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Pine Bark Extract | Combined Change in Systolic and Diastolic Blood Pressures From Baseline to Week 12. | -1.0 mm Hg |
| Placebo | Combined Change in Systolic and Diastolic Blood Pressures From Baseline to Week 12. | -1.9 mm Hg |
Secondary
ALT/SGPT
Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time frame: three months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pine Bark Extract | ALT/SGPT | 0.8 u/L | Standard Deviation 15.11 |
| Placebo | ALT/SGPT | -3.0 u/L | Standard Deviation 15.28 |
95% CI: [-1.6, 9.3]
Secondary
AST/SGOT
Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time frame: three months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pine Bark Extract | AST/SGOT | 0.2 u/L | Standard Deviation 4.9 |
| Placebo | AST/SGOT | 1.4 u/L | Standard Deviation 6.8 |
95% CI: [-3.4, 0.8]
Secondary
Body Mass Index
Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time frame: three months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pine Bark Extract | Body Mass Index | 0.1 kg/m^2 | Standard Deviation 0.4 |
| Placebo | Body Mass Index | -0.1 kg/m^2 | Standard Deviation 0.6 |
95% CI: [0, 0.4]
Secondary
C-reactive Protein
Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time frame: three months
Population: The data was analyzed on an intent-to-treat basis, with the last observation collected carried forward for participants with missing data at follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pine Bark Extract | C-reactive Protein | -0.2 nmol/L | Standard Deviation 2.56 |
| Placebo | C-reactive Protein | 0.3 nmol/L | Standard Deviation 2.9 |
95% CI: [-1.5, 0.5]
Secondary
Fasting Blood Glucose
Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time frame: three months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pine Bark Extract | Fasting Blood Glucose | -1.0 mg/dL | Standard Deviation 9.8 |
| Placebo | Fasting Blood Glucose | 0.1 mg/dL | Standard Deviation 8.7 |
95% CI: [-4.4, 2.3]
Secondary
Fasting Insulin
Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time frame: three months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pine Bark Extract | Fasting Insulin | 0.2 mg/dL | Standard Deviation 4.2 |
| Placebo | Fasting Insulin | -0.6 mg/dL | Standard Deviation 5.2 |
95% CI: [-0.9, 2.5]
Secondary
HDL
Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pine Bark Extract | HDL | -0.9 mg/dL | Standard Deviation 6 |
| Placebo | HDL | -1.3 mg/dL | Standard Deviation 5.6 |
95% CI: [-1.7, 2.5]
Secondary
HDL Particle Size
Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pine Bark Extract | HDL Particle Size | 1.0 nm | Standard Deviation 3.1 |
| Placebo | HDL Particle Size | 0.0 nm | Standard Deviation 4.2 |
95% CI: [0, 0.1]
Secondary
Hemoglobin A1c
Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time frame: three months
Population: The data was analyzed on an intent-to-treat basis, with the last observation collected carried forward for participants with missing data at follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pine Bark Extract | Hemoglobin A1c | -0.0 mg/dL | Standard Deviation 0.2 |
| Placebo | Hemoglobin A1c | -0.0 mg/dL | Standard Deviation 0.2 |
95% CI: [-0.1, 0.1]
Secondary
LDL
Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pine Bark Extract | LDL | 3.3 mg/dL | Standard Deviation 16.6 |
| Placebo | LDL | -1.1 mg/dL | Standard Deviation 19.7 |
95% CI: [-2.1, 10.8]
Secondary
LDL Particle Size
Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pine Bark Extract | LDL Particle Size | 31.4 nm | Standard Deviation 200.2 |
| Placebo | LDL Particle Size | 28.5 nm | Standard Deviation 248.5 |
95% CI: [-0.1, 0.3]
Secondary
Lipoprotein A
Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up). Calculated as (Pinebark\_Followup - Pinebark\_Baseline) - (Placebo\_Follow-up - Placebo\_Baseline)
Time frame: three months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pine Bark Extract | Lipoprotein A | -1.3 nmol/L | Standard Deviation 10.3 |
| Placebo | Lipoprotein A | 1.8 nmol/L | Standard Deviation 10 |
95% CI: [-6.8, 0.5]
Secondary
Total Cholesterol
Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pine Bark Extract | Total Cholesterol | 5.4 mg/dL | Standard Deviation 17.5 |
| Placebo | Total Cholesterol | -2.0 mg/dL | Standard Deviation 23.7 |
95% CI: [-0.1, 14.9]
Secondary
Triglycerides
Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time frame: three months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pine Bark Extract | Triglycerides | 17.2 mg/dL | Standard Deviation 50.6 |
| Placebo | Triglycerides | -1.0 mg/dL | Standard Deviation 63 |
95% CI: [-2.3, 38.7]
Secondary
Weight
Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pine Bark Extract | Weight | 0.6 lb | Standard Deviation 3.1 |
| Placebo | Weight | -0.6 lb | Standard Deviation 3.4 |
95% CI: [0.1, 2.4]