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UNDERSTANDING PINE BARK EXTRACT as 
an ALTERNATIVE TREATMENT (UPBEAT)
ORIENTATION FOR ANTIOXIDANT STUDY

Agenda

..Short presentation about the study 
..Break for additional questions
..Understand and sign consent forms
..Schedule your visits


Inside your packet:

..Study staff contact information
..Two consent forms (one copy is for our records)
..3-day food record + tips sheet
..Demographics form
..Appointment slip
..Calendar with sample visit



Objectives of Presentation

..What is interesting about pine bark extract?
..Who are we?
..Why are you here?
..What are you committing to?
..What are your rights as a participant?
..SIGN YOU UP!



BACKGROUND


History of Pine Bark

..Pine bark has been used as a food, tea, and medicine by Native 
American tribes for thousands of years
..The extract was discovered by Jacques Masquelierof the University 
of Bordeaux, France in 1947


..He read about a winter expedition in New York where a group of 
men survived by drinking tea made from pine bark
..The extract contains natural compounds called OPCs(oligomericproanthocyanidincomplexes)
..Also found in common foods: grape seeds, wine, cranberries, 
apples, pears, and pomegranates
..Potent antioxidants that may provide cardiovascular benefits



Health Benefits of Pine Bark

..Shandand others (2003) –480mg/day pine bark extract for 12 weeks
..7mmHg decrease in blood pressure
..Significant decrease in BMI and % body fat
..Liu and others (2004) –100mg/day pine bark extract for 12 weeks
..35 mg/dl decrease in blood glucose levels
..Reduced the need for blood pressure medications


..Davarajand others (2002) –150mg/day pine bark extract for 6 weeks 
..7% decrease in LDL levels
..14.5% increase in HDL levels


..Petrassiand others (2000) –200 to 300mg/day pine bark extract
..Improved circulation, less edema of the legs



Text Box: Other possible benefits:
Other possible benefits:
Text Box: Pine bark improves migraine headaches – Kaiser Permanente Dept. of Neurology (2006).
Pine bark reduces asthma and improves lung function – Hosseini (2001), Lau (2004).
Pine bark improves vessel function in patients with chronic venous insuffic
..Pine bark improves migraine headaches –Kaiser Permanente 
Dept. of Neurology (2006).
..Pine bark reducesasthmaand improves lung function –Hosseini(2001), Lau (2004).
..Pine bark improves vessel functionin patients with chronic 
venous insufficiency –Cesarone(2006).
..Pine bark reduces symptoms ofADHD in children –Trebaticka(2006). 
..Pine bark relieves menstrual cramps–Kohama(2004).
..Pine bark improves sexual function in men with erectile 
dysfunction –Stanislavov(2003).

But…

..Previous studies are flawed because they:
..Lacked a control group
..Lacked randomization
..Lacked enough participants
..Had poorly defined outcomes 
..Lacked correct statistical analyses


..By filling a knowledge gap, this study will provide 
important answers to both consumers and health 
professionals



PART A:

WHAT YOU MUST KNOW 

ABOUT THE STUDY


Stanford

Prevention

Research 

Center

..35-year history of research into 
the effects of:


Nutrition

Physical Activity

Smoking Cessation

Health Behaviors

..On heart disease, cancer, 
diabetes, bone health, and 
other conditions



Your Research Team

Randall S. Stafford, MD, PhD –Principal Investigator

Rebecca Drieling, MMQ –Research Director

Christopher Gardner, PhD –Co-Investigator

Jun Ma, MD, RD, PhD –Co-Investigator

Heather Klaftenegger–Research Assistant

Alexis Fields –Undergraduate Research Intern

Program on Prevention Outcomes and Practices


Purpose of Our Project

..Evaluate the effect of pine bark extract (Flavangenol®) 
on cardiovascular risk factors including: 


..Blood Pressure
..Blood Sugar Levels
..Cholesterol Levels


..Body Weight
..Markers of Systemic Inflammation


..Confirm the safety of pine bark



Eligibility Criteria

..Inclusion
..For age 18-34 years systolic blood pressure (SBP) between 
125 and 140 mmHg 
..For age > 35 years, SBP between 125 and 159 mmHg
..Body mass index (BMI) 25.0 to 34.9


..Exclusion
..Diastolic Blood Pressure (DBP) =100 mmHg
..Triglycerides (TG) =450 mg/dL
..Low Density Lipoprotein (LDL) =200 mg/dL
..Fasting blood glucose (FBG) =126 mg/dL



Warning levels that may require checking 
with your physician

..For age < 70 years:
..Systolic Blood Pressure >145 mmHg
..Diastolic Blood Pressure >95 mmHg
..Low Density Lipoprotein (LDL) >170 mg/dL
..Triglycerides (TG) >300 mg/dLor
..Fasting blood glucose (FBG) >110 mg/dL


..For age > 70 years:
..Systolic Blood Pressure >140mmHg
..Diastolic Blood Pressure >90mmHg and/or 
..Low Density Lipoprotein (LDL) >150mg/dL



Other Considerations

..Agree to refrain from taking medications that affect blood 
pressure, blood sugar or weight through the end of a 12 
week follow up.


..Agree to discontinue the use of supplements that are not 
vitamins or minerals for 12 weeks and go through a 4 
week wash-out period before enrollment.
..Agree to reduce the amount of vitamins and minerals to 
200% or less of the daily value. 



Study Design

Randomization

Pine Bark Supplement, n = 65 (200mg/day)

Placebo, n = 65 (0mg/day)

Total of 130 individuals in the study

Assigned by “CHANCE”NOT BY CHOICE

No bias of who gets what treatment

50 –50CHANCE 

65 individuals –Pine Bark supplement

65 individuals –placebo (control) group

NEITHER YOU OR THE STUDY STAFF WILL KNOW WHICH 
GROUP YOU ARE IN



Procedures

03 612

Week

1.Tablets




Procedures: 1. Tablets

..Will pick up supplement and/or drop off left over tablets at theGeneral 
Clinical Research Center at the following visits:


Baseline

3 weeks

6 weeks

12 weeks

..Take 4 Study Tablets Once a Day in the Morning. Total of 200 mgof Pine 
Bark Extract per day
..Expect to have extra tablets when you drop them off. 
..Make sure to bring them or bring the empty baggie if all tabletsare gone!



1.Tablets


2. Blood Pressure

Text Box: Procedures
Procedures03 612Week

Procedures: 2. Blood Pressure

..Primary outcome of the study


..Will be measured before collection of blood samples:


Twice at Baseline (3 to 7 days apart)

Once at 6 weeks

Twice at 12 weeks (3 to 7 days apart)

..Resting Blood Pressure
..If you feel rushed at your clinic visit, please ask your Nurse for a few 
extra minutes to relax.



Procedures: Other Measurements

..Weight
..Waist circumference
..These Measurements will be measured:


Twice at Baseline Visits (3 to 7 days apart)

Once at 6 weeks

Twice at 12 weeks (3 to 7 days apart)


1.Tablets


2. Blood Pressure

3. Blood Sampling

Text Box: Procedures
Procedures03 612Week

Procedures:3. Blood Sampling

..Blood samples will be obtained after an 8 hour fast


(e.g. from 10:00pm to 6:00am)

..5 blood samples over 12 weeks:


Twice at Baseline (3 to 7 days apart)

Once at 6 weeks

Twice at 12 weeks (3 to 7 days apart)

..Blood samples will be 20 cc’s (approximately 1 ½tablespoons) 


..Visits start at 7:30am Monday –Friday 


..General Clinical Research Center (GCRC), Stanford Hospital



Measurements from blood:

Blood GlucoseFasting blood glucose

Hemoglobin A1C

Fasting insulin

Cholesterol andLipid Panel

Inflammation Low density lipoprotein particle size

Lipoprotein A

C-Reactive protein

Liver FunctionAspartateaminotransferase(AST) 

AlanineAminotransferase(ALT)

You will receive your results at the end of the study.

All laboratory measures are free!!! 

A value of more than $400 per blood draw.


1.Tablets


2. Blood Pressure

3. Blood Sampling

4. Questionnaires

Text Box: Procedures
Procedures03 612Week

Procedures:4. Questionnaires

..General Information / Demographics 
..Complete during orientation meeting


..3-Day Food Records
..Record items consumed on a single day for 3 separate days
..Can but do not have to be consecutive days
..Must include two weekdays and one weekend day
..Read instructions and include brand name and size of foods
..Bring completed form to 2ndstudy visit
..We will mail you the second Food Record at 9 weeks
..Bring second completed form to 5th study visit
..Adverse Symptoms 
..Complete at 3rdvisit, 4thvisit, 5thvisit, and 6thvisit



Text Box: Procedures
Procedures03 612Week1.Tablets2. Blood Pressure3. Blood Sampling4. Questionnaires5. Compensation

Procedures:5. Compensation

..Total of $100 in compensation intended to partiallycompensate you for your inconvenienceand efforts


..Compensation Provided as Visa Gift Cards
..Redeemable anywhere that you can use a credit card
..Far more convenient than payment by check or cash


..Compensation Schedule
..Initial $25 mailed to you after visit 2
..Additional $30 mailed to you after visit 4
..Additional $45 mailed to you after visit 6
..Total $100



Time Commitment 

This DOES NOT include YOUR TRAVEL TIME to the Stanford 
campus

..Visit 1: 25 to 30 minutes
..Blood sampling and other measurements


..Visit 2: 40 to 60 minutes (visits before 8:00am may take longer)
..Bring completed 3-Day Food Record
..Blood sampling, other measurements, receive study tablets
..Compensation: $25 gift card


..Visit 3: 15 to 20 minutes
..Exchange study tablets and complete adverse events form



Time Commitment

..Visit 4: 30 to 40 minutes
..Blood sampling, other measurements, exchange study tablets, 
and complete adverse events form
..Compensation: $30 gift card


..Visit 5: 25 to 30 minutes
..Bring completed 3-Day Food Record
..Blood sampling, other measurements, and complete adverse 
events form


..Visit 6: 25-30 minutes
..Blood sampling, other measurements, return study tablets, and 
complete adverse events form
..Compensation: $45 gift card



Time Commitment

..Take study tablets:
..1 minute each day to take study tablets with a non-alcoholic 
beverage of your choice


..3-Day food records
..Must include two weekdays and one weekend day (they can, 
but do not have to be consecutive days)
..45 to 60 minutes prior to the 2ndvisitand prior to the 5thvisit
..Bring to visit 2 and visit 5


..Using your Visa gift cards
..5-30 minutes on each of three occasions



Potential Benefits

..Improvement in blood pressure (?)
..Other cardiovascular health benefits (?)


(glucose and cholesterol levels, weight, inflammatory markers)

..Free physiological and laboratory measurements


..Knowledge about cardiovascular risk factors, nutrition, and health


Text Box: WE CANNOT AND DO NOT GUARANTEE OR PROMISE
THAT YOU WILL RECEIVE ANY BENEFITS FROM THIS STUDY
WE CANNOT AND DO NOT GUARANTEE OR PROMISETHAT YOU WILL RECEIVE ANY BENEFITS FROM THIS STUDY

Potential Risks and Discomforts

..Blood Sampling
..Discomfort from needle, possible bruising


..Potential side effects from supplement: 
gastrointestinal discomfort


nausea

dizziness

headache

sleepiness

urinary retention

urinary frequency

constipation 

increased perspiration


Costs and Funding Source

..No cost to you for your participation
..All study costs are funded by Toyo Shinyaku Co., Ltd.
..You will obtain free information about your lab test 
results at the end of the study


..Compensation of $100 


(plus parking permits totaling $25 in value)


PART B: 

GENERAL INFORMATION 

ABOUT BEING A RESEARCH 

PARTICIPANT


Participation in Other Studies

Allowed only if informed approval is obtained 
from the investigators of both projects


Women of Childbearing Age

..You can’t be in this study if you are pregnant or 
lactating


..You should not join this study if you are planning 
to become pregnant in the next year
..Any nutritional supplement may involve 
unforeseen risks to you and your unborn fetus



Blood: Sampling and Storage Issues

..No genetic testing
..No development of commercial products
..No use of samples without your permission
..Any extra blood will be discarded



Right to Refuse or Withdraw

..Your participation in this research study is entirely voluntary –you 
may choose to withdraw at ANY TIME (and this decision will not 
affect your medical/health care)


..There are several reasons for which you may be withdrawn from 
the study:
..Failure to follow instructions
..Continuation determined to be harmful to you
..You need treatment not provided by study
..Study is cancelled
..Other administrative reasons 
..Unanticipated circumstances



Personal Health Information (PHI)

..Name
..Phone number
..Address
..Date of birth 


..All PHI and clinical information will be destroyed after 
6 years. 
..Your data will not be published 
..Your identity will not be revealed



Confidentiality/Anonymity

..You will be assigned a second ID number
..Your data will be kept in a locked room or in the 
case of electronic files, in a password protected 
manner
..Absolute confidentiality cannot be guaranteed


Patient information may be provided to Federal and 
other regulatory agencies as required


Alternatives

..Nutrition –Low sodium diet, plant based diet, 
weight loss
..Talk to a Registered Dietitian
..Prescription Medications –
..Talk to your physician regarding whether it is 
reasonable for you to participate in this study



Financial Interest Disclosure

..No Conflict of Interest
..Neither the investigators nor Stanford University 
have stock or investment interests in Toyo 
Shinyaku Co., Ltd.



Questions

..Call the Principal Investigator:


Randall S. Stafford, MD, PhD 

(650) 724-2400


Complications

Administrative Panel on 

Human Subjects in Medical Research

Stanford University

Stanford, CA 94305-501 

Call: (650) 723-5244


New Information

..You will be informed if new information arises



Human Subjects Bill of Rights

..See Page 12 of Your Consent Form



THANK YOU!

FOR ATTENDING THE UPBEAT 
STUDY ORIENTATION