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

• ClinicalTrials.gov Identifier: NCT00425945
• Recruitment Status: Completed
• First Posted: January 24, 2007
• Results First Posted: April 2, 2014
• Last Update Posted: April 2, 2014
• Sponsor: Stanford University
• Collaborator: Funded by Toyo Shinyaku Co Ltd
• Information provided by (Responsible Party): Randall Stafford, Stanford University

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Condition: Hypertension
• Intervention: Drug: Pine Bark Extract (Flavangenol®)
• Enrollment: 130

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.

Arm/Group Title	Pine Bark Extract	Placebo
Arm/Group Description	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 delivered as four tablets matching the active product; four tablets taken daily orally.
Period Title: Overall Study
Started	64	66
Completed	60	61
Not Completed	4	5
Reason Not Completed
Concern about Supplement	2	0
Inconvenience	0	2
Lost to Follow-up	0	2
Began hypertension medication	1	0
Began cancer treatments	1	0
Moved from area	0	1

Baseline Characteristics

Arm/Group Title		Pine Bark Extract	Placebo	Total
Arm/Group Description		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 delivered as four tablets matching the active product; four tablets taken daily orally.	Total of all reporting groups
Overall Number of Baseline Participants		64	66	130
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	64 participants	66 participants	130 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	51 79.7%	55 83.3%	106 81.5%
	>=65 years	13 20.3%	11 16.7%	24 18.5%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	64 participants	66 participants	130 participants
		56.9 (9.8)	53.9 (12.0)	55.4 (11.0)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	64 participants	66 participants	130 participants
	Female	25 39.1%	23 34.8%	48 36.9%
	Male	39 60.9%	43 65.2%	82 63.1%

Outcome Measures

1. Primary Outcome

Title	Combined Change in Systolic and Diastolic Blood Pressures From Baseline to Week 12.
Description	Mean at Week 12 observation minus mean at Baseline observation.
Time Frame	three months

Outcome Measure Data

Analysis Population Description

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/Group Title	Pine Bark Extract	Placebo
Arm/Group Description:	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 delivered as four tablets matching the active product; four tablets taken daily orally.
Overall Number of Participants Analyzed	64	66
Mean (95% Confidence Interval); Unit of Measure: mm Hg
	-1.0; (-4.2 to 2.1)	-1.9; (-5.5 to 1.7)

2. Secondary Outcome

Title	Total Cholesterol
Description	Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pine Bark Extract (Net Change)	Placebo (Net Change)
Arm/Group Description:	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 delivered as four tablets matching the active product; four tablets taken daily orally.
Overall Number of Participants Analyzed	60	62
Mean (Standard Deviation); Unit of Measure: mg/dL
	5.4 (17.5)	-2.0 (23.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pine Bark Extract (Net Change), Placebo (Net Change)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	7.3
	Confidence Interval	(2-Sided) 95%; -0.1 to 14.9
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	LDL
Description	Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pine Bark Extract (Net Change)	Placebo (Net Change)
Arm/Group Description:	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 delivered as four tablets matching the active product; four tablets taken daily orally.
Overall Number of Participants Analyzed	60	62
Mean (Standard Deviation); Unit of Measure: mg/dL
	3.3 (16.6)	-1.1 (19.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pine Bark Extract (Net Change), Placebo (Net Change)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	4.4
	Confidence Interval	(2-Sided) 95%; -2.1 to 10.8
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	HDL
Description	Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pine Bark Extract (Net Change)	Placebo (Net Change)
Arm/Group Description:	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 delivered as four tablets matching the active product; four tablets taken daily orally.
Overall Number of Participants Analyzed	60	62
Mean (Standard Deviation); Unit of Measure: mg/dL
	-0.9 (6.0)	-1.3 (5.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pine Bark Extract (Net Change), Placebo (Net Change)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -1.7 to 2.5
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Triglycerides
Description	Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time Frame	three months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pine Bark Extract (Net Change)	Placebo (Net Change)
Arm/Group Description:	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 delivered as four tablets matching the active product; four tablets taken daily orally.
Overall Number of Participants Analyzed	60	62
Mean (Standard Deviation); Unit of Measure: mg/dL
	17.2 (50.6)	-1.0 (63.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pine Bark Extract (Net Change), Placebo (Net Change)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	18.2
	Confidence Interval	(2-Sided) 95%; -2.3 to 38.7
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	LDL Particle Size
Description	Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pine Bark Extract (Net Change)	Placebo (Net Change)
Arm/Group Description:	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 delivered as four tablets matching the active product; four tablets taken daily orally.
Overall Number of Participants Analyzed	59	62
Mean (Standard Deviation); Unit of Measure: nm
	31.4 (200.2)	28.5 (248.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pine Bark Extract (Net Change), Placebo (Net Change)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -0.1 to 0.3
	Estimation Comments	[Not Specified]

7. Secondary Outcome

Title	HDL Particle Size
Description	Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pine Bark Extract (Net Change)	Placebo (Net Change)
Arm/Group Description:	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 delivered as four tablets matching the active product; four tablets taken daily orally.
Overall Number of Participants Analyzed	59	62
Mean (Standard Deviation); Unit of Measure: nm
	1.0 (3.1)	0.0 (4.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pine Bark Extract (Net Change), Placebo (Net Change)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.0 to 0.1
	Estimation Comments	[Not Specified]

8. Secondary Outcome

Title	Lipoprotein A
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pine Bark Extract (Net Change)	Placebo (Net Change)
Arm/Group Description:	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 delivered as four tablets matching the active product; four tablets taken daily orally.
Overall Number of Participants Analyzed	59	60
Mean (Standard Deviation); Unit of Measure: nmol/L
	-1.3 (10.3)	1.8 (10.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pine Bark Extract (Net Change), Placebo (Net Change)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3.2
	Confidence Interval	(2-Sided) 95%; -6.8 to 0.5
	Estimation Comments	[Not Specified]

9. Secondary Outcome

Title	C-reactive Protein
Description	Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time Frame	three months

Outcome Measure Data

Analysis Population Description

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/Group Title	Pine Bark Extract (Net Change)	Placebo (Net Change)
Arm/Group Description:	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 delivered as four tablets matching the active product; four tablets taken daily orally.
Overall Number of Participants Analyzed	60	63
Mean (Standard Deviation); Unit of Measure: nmol/L
	-0.2 (2.56)	0.3 (2.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pine Bark Extract (Net Change), Placebo (Net Change)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -1.5 to 0.5
	Estimation Comments	[Not Specified]

10. Secondary Outcome

Title	Body Mass Index
Description	Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time Frame	three months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pine Bark Extract (Net Change)	Placebo (Net Change)
Arm/Group Description:	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 delivered as four tablets matching the active product; four tablets taken daily orally.
Overall Number of Participants Analyzed	60	62
Mean (Standard Deviation); Unit of Measure: kg/m^2
	0.1 (0.4)	-0.1 (0.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pine Bark Extract (Net Change), Placebo (Net Change)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; 0.0 to 0.4
	Estimation Comments	[Not Specified]

11. Secondary Outcome

Title	Weight
Description	Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pine Bark Extract (Net Change)	Placebo (Net Change)
Arm/Group Description:	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 delivered as four tablets matching the active product; four tablets taken daily orally.
Overall Number of Participants Analyzed	60	62
Mean (Standard Deviation); Unit of Measure: lb
	0.6 (3.1)	-0.6 (3.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pine Bark Extract (Net Change), Placebo (Net Change)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.2
	Confidence Interval	(2-Sided) 95%; 0.1 to 2.4
	Estimation Comments	[Not Specified]

12. Secondary Outcome

Title	Fasting Blood Glucose
Description	Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time Frame	three months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pine Bark Extract (Net Change)	Placebo (Net Change)
Arm/Group Description:	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 delivered as four tablets matching the active product; four tablets taken daily orally.
Overall Number of Participants Analyzed	59	62
Mean (Standard Deviation); Unit of Measure: mg/dL
	-1.0 (9.8)	0.1 (8.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pine Bark Extract (Net Change), Placebo (Net Change)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -4.4 to 2.3
	Estimation Comments	[Not Specified]

13. Secondary Outcome

Title	Fasting Insulin
Description	Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time Frame	three months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pine Bark Extract (Net Change)	Placebo (Net Change)
Arm/Group Description:	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 delivered as four tablets matching the active product; four tablets taken daily orally.
Overall Number of Participants Analyzed	60	62
Mean (Standard Deviation); Unit of Measure: mg/dL
	0.2 (4.2)	-0.6 (5.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pine Bark Extract (Net Change), Placebo (Net Change)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.8
	Confidence Interval	(2-Sided) 95%; -0.9 to 2.5
	Estimation Comments	[Not Specified]

14. Secondary Outcome

Title	Hemoglobin A1c
Description	Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time Frame	three months

Outcome Measure Data

Analysis Population Description

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/Group Title	Pine Bark Extract (Net Change)	Placebo (Net Change)
Arm/Group Description:	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 delivered as four tablets matching the active product; four tablets taken daily orally.
Overall Number of Participants Analyzed	58	62
Mean (Standard Deviation); Unit of Measure: mg/dL
	-0.0 (0.2)	-0.0 (0.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pine Bark Extract (Net Change), Placebo (Net Change)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.1 to 0.1
	Estimation Comments	[Not Specified]

15. Secondary Outcome

Title	ALT/SGPT
Description	Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time Frame	three months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pine Bark Extract (Net Change)	Placebo (Net Change)
Arm/Group Description:	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 delivered as four tablets matching the active product; four tablets taken daily orally.
Overall Number of Participants Analyzed	60	62
Mean (Standard Deviation); Unit of Measure: u/L
	0.8 (15.11)	-3.0 (15.28)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pine Bark Extract (Net Change), Placebo (Net Change)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.8
	Confidence Interval	(2-Sided) 95%; -1.6 to 9.3
	Estimation Comments	[Not Specified]

16. Secondary Outcome

Title	AST/SGOT
Description	Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time Frame	three months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pine Bark Extract (Net Change)	Placebo (Net Change)
Arm/Group Description:	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 delivered as four tablets matching the active product; four tablets taken daily orally.
Overall Number of Participants Analyzed	60	62
Mean (Standard Deviation); Unit of Measure: u/L
	0.2 (4.9)	1.4 (6.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pine Bark Extract (Net Change), Placebo (Net Change)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; -3.4 to 0.8
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Pine Bark Extract		Placebo
Arm/Group Description	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 delivered as four tablets matching the active product; four tablets taken daily orally.
All-Cause Mortality
	Pine Bark Extract		Placebo
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Pine Bark Extract		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/64 (1.56%)		2/66 (3.03%)
Musculoskeletal and connective tissue disorders
Emergency Department † [1]	0/64 (0.00%)	0	2/66 (3.03%)	2
Surgical and medical procedures
Hospitalized † [2]	1/64 (1.56%)	1	0/66 (0.00%)	0
† Indicates events were collected by systematic assessment; [1] Dislocated toe; Received tetanus booster after stepping on a nail; [2] Hip Surgery
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Pine Bark Extract		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/64 (37.50%)		29/66 (43.94%)
Gastrointestinal disorders
Gastrointestinal Discomfort (week 3) †	12/64 (18.75%)	12	9/66 (13.64%)	9
Gastrointestinal Discomfort (week 6) †	8/64 (12.50%)	8	3/66 (4.55%)	3
Nause (week 12) †	6/64 (9.38%)	6	1/66 (1.52%)	1
General disorders
Sleepiness (week 12) †	5/64 (7.81%)	5	12/66 (18.18%)	12
Increased Perspiration (week 6) †	5/64 (7.81%)	5	1/66 (1.52%)	1
Other (week 6) †	7/64 (10.94%)	7	2/66 (3.03%)	2
Nervous system disorders
Dizziness (week 3) †	1/64 (1.56%)	1	5/66 (7.58%)	5
Dizziness (week 12) †	3/64 (4.69%)	3	7/66 (10.61%)	7
Headache (week 12) †	8/64 (12.50%)	8	13/66 (19.70%)	13
Insomnia (week 6) †	4/64 (6.25%)	4	11/66 (16.67%)	11
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Dr. Randall Stafford
• Organization: Stanford University School of Medicine
• Phone: 650-724-2400
• EMail: rstafford@stanford.edu

Publications of Results:

Drieling RL, Gardner CD, Ma J, Ahn DK, Stafford RS. No beneficial effects of pine bark extract on cardiovascular disease risk factors. Arch Intern Med. 2010 Sep 27;170(17):1541-7. doi: 10.1001/archinternmed.2010.310.

• Responsible Party: Randall Stafford, Stanford University
• ClinicalTrials.gov Identifier: NCT00425945
• Other Study ID Numbers: 37698
• First Submitted: January 23, 2007
• First Posted: January 24, 2007
• Results First Submitted: March 29, 2013
• Results First Posted: April 2, 2014
• Last Update Posted: April 2, 2014