Trial Outcomes & Findings for Understanding Pine Bark Extract as an Alternative Treatment (UPBEAT) Study (NCT NCT00425945)

NCT ID: NCT00425945

Last Updated: 2014-04-02

Results Overview

Mean at Week 12 observation minus mean at Baseline observation.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 130 participants
• Primary outcome timeframe: three months
• Results posted on: 2014-04-02

Participant Flow

Participants were recruited from the local community through the use of radio and print advertisements between January 31, 2007 and May 31, 2008.

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.

Participant milestones

Measure	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. Flavangenol is a brand of pine bark extract manufactured by Toyo Shinyaku of Saga, Japan. Dosage delivered as four tablets, 50 mg per tablet, taken once per day orally for 12 weeks.	Placebo Placebo delivered as four tablets matching the active product; four tablets taken daily orally.
Overall Study STARTED	64	66
Overall Study COMPLETED	60	61
Overall Study NOT COMPLETED	4	5

Reasons for withdrawal

Measure	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. Flavangenol is a brand of pine bark extract manufactured by Toyo Shinyaku of Saga, Japan. Dosage delivered as four tablets, 50 mg per tablet, taken once per day orally for 12 weeks.	Placebo Placebo delivered as four tablets matching the active product; four tablets taken daily orally.
Overall Study Concern about Supplement	2	0
Overall Study Inconvenience	0	2
Overall Study Lost to Follow-up	0	2
Overall Study Began hypertension medication	1	0
Overall Study Began cancer treatments	1	0
Overall Study Moved from area	0	1

Baseline Characteristics

Understanding Pine Bark Extract as an Alternative Treatment (UPBEAT) Study

Baseline characteristics by cohort

Measure	Pine Bark Extract n=64 Participants 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.	Placebo n=66 Participants Placebo delivered as four tablets matching the active product; four tablets taken daily orally.	Total n=130 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	51 Participants n=5 Participants	55 Participants n=7 Participants	106 Participants n=5 Participants
Age, Categorical >=65 years	13 Participants n=5 Participants	11 Participants n=7 Participants	24 Participants n=5 Participants
Age, Continuous	56.9 years STANDARD_DEVIATION 9.8 • n=5 Participants	53.9 years STANDARD_DEVIATION 12.0 • n=7 Participants	55.4 years STANDARD_DEVIATION 11.0 • n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	23 Participants n=7 Participants	48 Participants n=5 Participants
Sex: Female, Male Male	39 Participants n=5 Participants	43 Participants n=7 Participants	82 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Mean at Week 12 observation minus mean at Baseline observation.

Outcome measures

Measure	Pine Bark Extract n=64 Participants 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. Flavangenol is a brand of pine bark extract manufactured by Toyo Shinyaku of Saga, Japan. Dosage delivered as four tablets, 50 mg per tablet, taken once per day orally for 12 weeks.	Placebo n=66 Participants Placebo delivered as four tablets matching the active product; four tablets taken daily orally.
Combined Change in Systolic and Diastolic Blood Pressures From Baseline to Week 12.	-1.0 mm Hg Interval -4.2 to 2.1	-1.9 mm Hg Interval -5.5 to 1.7

SECONDARY outcome

Timeframe: 3 months

Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).

Outcome measures

Measure	Pine Bark Extract n=60 Participants 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. Flavangenol is a brand of pine bark extract manufactured by Toyo Shinyaku of Saga, Japan. Dosage delivered as four tablets, 50 mg per tablet, taken once per day orally for 12 weeks.	Placebo n=62 Participants Placebo delivered as four tablets matching the active product; four tablets taken daily orally.
Total Cholesterol	5.4 mg/dL Standard Deviation 17.5	-2.0 mg/dL Standard Deviation 23.7

SECONDARY outcome

Timeframe: 3 months

Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).

Outcome measures

Measure	Pine Bark Extract n=60 Participants 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. Flavangenol is a brand of pine bark extract manufactured by Toyo Shinyaku of Saga, Japan. Dosage delivered as four tablets, 50 mg per tablet, taken once per day orally for 12 weeks.	Placebo n=62 Participants Placebo delivered as four tablets matching the active product; four tablets taken daily orally.
LDL	3.3 mg/dL Standard Deviation 16.6	-1.1 mg/dL Standard Deviation 19.7

SECONDARY outcome

Timeframe: 3 months

Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).

Outcome measures

Measure	Pine Bark Extract n=60 Participants 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. Flavangenol is a brand of pine bark extract manufactured by Toyo Shinyaku of Saga, Japan. Dosage delivered as four tablets, 50 mg per tablet, taken once per day orally for 12 weeks.	Placebo n=62 Participants Placebo delivered as four tablets matching the active product; four tablets taken daily orally.
HDL	-0.9 mg/dL Standard Deviation 6.0	-1.3 mg/dL Standard Deviation 5.6

SECONDARY outcome

Timeframe: three months

Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).

Outcome measures

Measure	Pine Bark Extract n=60 Participants 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. Flavangenol is a brand of pine bark extract manufactured by Toyo Shinyaku of Saga, Japan. Dosage delivered as four tablets, 50 mg per tablet, taken once per day orally for 12 weeks.	Placebo n=62 Participants Placebo delivered as four tablets matching the active product; four tablets taken daily orally.
Triglycerides	17.2 mg/dL Standard Deviation 50.6 • Interval -0.1 to 0.3	-1.0 mg/dL Standard Deviation 63.0 • Interval 0.0 to 0.1

SECONDARY outcome

Timeframe: 3 months

Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).

Outcome measures

Measure	Pine Bark Extract n=59 Participants 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. Flavangenol is a brand of pine bark extract manufactured by Toyo Shinyaku of Saga, Japan. Dosage delivered as four tablets, 50 mg per tablet, taken once per day orally for 12 weeks.	Placebo n=62 Participants Placebo delivered as four tablets matching the active product; four tablets taken daily orally.
LDL Particle Size	31.4 nm Standard Deviation 200.2	28.5 nm Standard Deviation 248.5

SECONDARY outcome

Timeframe: 3 months

Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).

Outcome measures

Measure	Pine Bark Extract n=59 Participants 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. Flavangenol is a brand of pine bark extract manufactured by Toyo Shinyaku of Saga, Japan. Dosage delivered as four tablets, 50 mg per tablet, taken once per day orally for 12 weeks.	Placebo n=62 Participants Placebo delivered as four tablets matching the active product; four tablets taken daily orally.
HDL Particle Size	1.0 nm Standard Deviation 3.1	0.0 nm Standard Deviation 4.2

SECONDARY outcome

Timeframe: 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)

Outcome measures

Measure	Pine Bark Extract n=59 Participants 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. Flavangenol is a brand of pine bark extract manufactured by Toyo Shinyaku of Saga, Japan. Dosage delivered as four tablets, 50 mg per tablet, taken once per day orally for 12 weeks.	Placebo n=60 Participants Placebo delivered as four tablets matching the active product; four tablets taken daily orally.
Lipoprotein A	-1.3 nmol/L Standard Deviation 10.3 • Interval -6.8 to 0.5	1.8 nmol/L Standard Deviation 10.0

SECONDARY outcome

Timeframe: 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.

Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).

Outcome measures

Measure	Pine Bark Extract n=60 Participants 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. Flavangenol is a brand of pine bark extract manufactured by Toyo Shinyaku of Saga, Japan. Dosage delivered as four tablets, 50 mg per tablet, taken once per day orally for 12 weeks.	Placebo n=63 Participants Placebo delivered as four tablets matching the active product; four tablets taken daily orally.
C-reactive Protein	-0.2 nmol/L Standard Deviation 2.56 • Interval -1.5 to 0.5	0.3 nmol/L Standard Deviation 2.9

SECONDARY outcome

Timeframe: three months

Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).

Outcome measures

Measure	Pine Bark Extract n=60 Participants 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. Flavangenol is a brand of pine bark extract manufactured by Toyo Shinyaku of Saga, Japan. Dosage delivered as four tablets, 50 mg per tablet, taken once per day orally for 12 weeks.	Placebo n=62 Participants Placebo delivered as four tablets matching the active product; four tablets taken daily orally.
Body Mass Index	0.1 kg/m^2 Standard Deviation 0.4 • Interval 0.0 to 0.4	-0.1 kg/m^2 Standard Deviation 0.6

SECONDARY outcome

Timeframe: 3 months

Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).

Outcome measures

Measure	Pine Bark Extract n=60 Participants 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. Flavangenol is a brand of pine bark extract manufactured by Toyo Shinyaku of Saga, Japan. Dosage delivered as four tablets, 50 mg per tablet, taken once per day orally for 12 weeks.	Placebo n=62 Participants Placebo delivered as four tablets matching the active product; four tablets taken daily orally.
Weight	0.6 lb Standard Deviation 3.1	-0.6 lb Standard Deviation 3.4

SECONDARY outcome

Timeframe: three months

Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).

Outcome measures

Measure	Pine Bark Extract n=59 Participants 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. Flavangenol is a brand of pine bark extract manufactured by Toyo Shinyaku of Saga, Japan. Dosage delivered as four tablets, 50 mg per tablet, taken once per day orally for 12 weeks.	Placebo n=62 Participants Placebo delivered as four tablets matching the active product; four tablets taken daily orally.
Fasting Blood Glucose	-1.0 mg/dL Standard Deviation 9.8 • Interval -4.4 to 2.3	0.1 mg/dL Standard Deviation 8.7

SECONDARY outcome

Timeframe: three months

Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).

Outcome measures

Measure	Pine Bark Extract n=60 Participants 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. Flavangenol is a brand of pine bark extract manufactured by Toyo Shinyaku of Saga, Japan. Dosage delivered as four tablets, 50 mg per tablet, taken once per day orally for 12 weeks.	Placebo n=62 Participants Placebo delivered as four tablets matching the active product; four tablets taken daily orally.
Fasting Insulin	0.2 mg/dL Standard Deviation 4.2 • Interval -0.9 to 2.5	-0.6 mg/dL Standard Deviation 5.2

SECONDARY outcome

Timeframe: 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.

Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).

Outcome measures

Measure	Pine Bark Extract n=58 Participants 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. Flavangenol is a brand of pine bark extract manufactured by Toyo Shinyaku of Saga, Japan. Dosage delivered as four tablets, 50 mg per tablet, taken once per day orally for 12 weeks.	Placebo n=62 Participants Placebo delivered as four tablets matching the active product; four tablets taken daily orally.
Hemoglobin A1c	-0.0 mg/dL Standard Deviation 0.2 • Interval -0.1 to 0.1	-0.0 mg/dL Standard Deviation 0.2

SECONDARY outcome

Timeframe: three months

Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).

Outcome measures

Measure	Pine Bark Extract n=60 Participants 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. Flavangenol is a brand of pine bark extract manufactured by Toyo Shinyaku of Saga, Japan. Dosage delivered as four tablets, 50 mg per tablet, taken once per day orally for 12 weeks.	Placebo n=62 Participants Placebo delivered as four tablets matching the active product; four tablets taken daily orally.
ALT/SGPT	0.8 u/L Standard Deviation 15.11 • Interval -1.6 to 9.3	-3.0 u/L Standard Deviation 15.28

SECONDARY outcome

Timeframe: three months

Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).

Outcome measures

Measure	Pine Bark Extract n=60 Participants 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. Flavangenol is a brand of pine bark extract manufactured by Toyo Shinyaku of Saga, Japan. Dosage delivered as four tablets, 50 mg per tablet, taken once per day orally for 12 weeks.	Placebo n=62 Participants Placebo delivered as four tablets matching the active product; four tablets taken daily orally.
AST/SGOT	0.2 u/L Standard Deviation 4.9 • Interval -3.4 to 0.8	1.4 u/L Standard Deviation 6.8

Adverse Events

Pine Bark Extract

Serious events: 1 serious events

Other events: 24 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Measure	Pine Bark Extract n=64 participants at risk 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. Flavangenol is a brand of pine bark extract manufactured by Toyo Shinyaku of Saga, Japan. Dosage delivered as four tablets, 50 mg per tablet, taken once per day orally for 12 weeks.	Placebo n=66 participants at risk Placebo delivered as four tablets matching the active product; four tablets taken daily orally.
Surgical and medical procedures Hospitalized	1.6% 1/64 • Number of events 1	0.00% 0/66
Musculoskeletal and connective tissue disorders Emergency Department	0.00% 0/64	3.0% 2/66 • Number of events 2

Other adverse events

Measure	Pine Bark Extract n=64 participants at risk 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. Flavangenol is a brand of pine bark extract manufactured by Toyo Shinyaku of Saga, Japan. Dosage delivered as four tablets, 50 mg per tablet, taken once per day orally for 12 weeks.	Placebo n=66 participants at risk Placebo delivered as four tablets matching the active product; four tablets taken daily orally.
Gastrointestinal disorders Gastrointestinal Discomfort (week 3)	18.8% 12/64 • Number of events 12	13.6% 9/66 • Number of events 9
Gastrointestinal disorders Gastrointestinal Discomfort (week 6)	12.5% 8/64 • Number of events 8	4.5% 3/66 • Number of events 3
Gastrointestinal disorders Nause (week 12)	9.4% 6/64 • Number of events 6	1.5% 1/66 • Number of events 1
Nervous system disorders Dizziness (week 3)	1.6% 1/64 • Number of events 1	7.6% 5/66 • Number of events 5
Nervous system disorders Dizziness (week 12)	4.7% 3/64 • Number of events 3	10.6% 7/66 • Number of events 7
Nervous system disorders Headache (week 12)	12.5% 8/64 • Number of events 8	19.7% 13/66 • Number of events 13
General disorders Sleepiness (week 12)	7.8% 5/64 • Number of events 5	18.2% 12/66 • Number of events 12
Nervous system disorders Insomnia (week 6)	6.2% 4/64 • Number of events 4	16.7% 11/66 • Number of events 11
General disorders Increased Perspiration (week 6)	7.8% 5/64 • Number of events 5	1.5% 1/66 • Number of events 1
General disorders Other (week 6)	10.9% 7/64 • Number of events 7	3.0% 2/66 • Number of events 2

Additional Information

Dr. Randall Stafford

Stanford University School of Medicine

Phone: 650-724-2400

Email: rstafford@stanford.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place