Advancing Niacin by Inhibiting Flushing (ANTI-FLUSH)

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT00913081
• Collaborator: Abbott (Industry)
• Enrollment: 17
• Locations: 2
• Arms: 4
• Duration (Months): 10
• Patients Per Site: 8.5
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

Niacin, or vitamin B3, is known to improve cholesterol disorders and is the most effective drug to raise HDL, or the "good cholesterol". The use of niacin has been limited because of a peculiar adverse effect referred to as "flushing', which consists of redness, warmth, tingling and burning. A recent animal study suggests that flavonoids may prevent flushing due to niacin better than drugs like aspirin. The ANTI-FLUSH study is being done to assess whether a presently available dietary supplement known as quercetin, which is a flavonoid, can reduce the flushing that occurs with niacin. We will also assess whether using quercetin to prevent flushing from niacin, can improve how niacin lowers cholesterol.

Condition or Disease	Intervention/Treatment	Phase
Flushing	Dietary Supplement: Quercetin; Dietary Supplement: Placebo	Phase 4

Detailed Description

This study involves people between 21 and 75 years. It will be conducted over a period of 8 weeks, with 4 visits, each separated by 2 weeks. The duration of each visit is 9-10 hours. We will test a different dose of quercetin in each visit.

Study Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Supportive Care
• Official Title: Advancing Niacin by Inhibiting FLUSHing: (ANTI-FLUSH)
• Study Start Date: Feb 1, 2009
• Actual Primary Completion Date: Aug 1, 2009
• Actual Study Completion Date: Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Quercetin 500 mg Quercetin 500 mg once, administered one hour before 500 mg immediate-release niacin	Dietary Supplement: Quercetin; Quercetin 500, 1000, or 2000 mg PO one time; Other Names: Isoquercetin
Experimental: Quercetin 1000 mg Quercetin 1000 mg once, administered one hour before 500 mg immediate-release niacin	Dietary Supplement: Quercetin; Quercetin 500, 1000, or 2000 mg PO one time; Other Names: Isoquercetin
Experimental: Quercetin 2000 mg Quercetin 2000 mg once, administered one hour before 500 mg immediate-release niacin	Dietary Supplement: Quercetin; Quercetin 500, 1000, or 2000 mg PO one time; Other Names: Isoquercetin
Placebo Comparator: Placebo Placebo once, administered one hour before 500 mg immediate-release niacin	Dietary Supplement: Placebo; Placebo PO one time

Outcome Measures

Primary Outcome Measures

1. Whether Quercetin Dose-dependently Reduces Laser Doppler Flux Index Primary Peak Following Immediate-release Niacin [8 hour period]

   Laser Doppler flowmetry at the malar eminence measures blood flow quantitatively as red blood cell flux. Flux index is the fold-change in flux over baseline. Flux index primary peak is the maximum flux index between 0-4 hours after niacin.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Men and women from the age of 21 to 75, inclusive - 16 subjects, 8 men, 8 women.

2. Ability to understand and agree to informed consent.

3. Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures.

Exclusion Criteria:

1. Contra-indications or known intolerance to the study medications.

2. History of congestive heart failure, carcinoid, rosacea, renal failure (GFR<60 ml/min/m2).

3. Active liver disease.

4. Active diabetes (defined as any history of type 1 diabetes, or history of type 2 diabetes plus one or more of the following: fasting glucose>= 126mg/dL at screening or use of anti-diabetic medications within 12 months, or glucose>200mg/dL 2 hours after a 75 g oral glucose challenge within 12 months.

5. History of major surgery within the past 6 weeks, or anticipated major surgery during the course of the study, or any history of organ transplant.

6. History of drug abuse within the past 3 years, or regular alcohol use of greater than 14 drinks per week.

7. Women who are pregnant, plan to conceive or lactate.

8. Peri-menopausal women or women currently experiencing flushing.

9. Currently taking vasoactive medications, anti-hypertensives, anti-histamines, Selective Serotonin Re-uptake Inhibitors (SSRIs), NSAIDS, oral steroids, leukotriene inhibitors, supplemental quercetin and > 50mg niacin.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CTRC Univ. of Penn - Andrew Mutch Bldg., 4th floor	Phila	Pennsylvania	United States	19104
2	University of Pennsylvania	Phila	Pennsylvania	United States	19104

Sponsors and Collaborators

• University of Pennsylvania
• Abbott

Investigators

• Principal Investigator: Richard L. Dunbar, MD, University of Pennsylvania

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT00913081
• Other Study ID Numbers: IRB #808911
• First Posted: Jun 3, 2009
• Last Update Posted: Mar 5, 2015
• Last Verified: Nov 1, 2011

• Keywords provided by University of Pennsylvania: Skin; pharmacology; metabolism; lipid
• Additional relevant MeSH terms: Flushing; Quercetin

Study Results

Participant Flow

Recruitment Details	The study enrolled healthy volunteers aged 21 to 75 years. Subjects were recruited at the University of Pennsylvania CTRC following a screening visit to confirm eligibility based on an interview reviewing their health status and medication use, baseline laboratory assessment and the ability to tolerate a 500 mg dose of immediate-release niacin
Pre-assignment Detail	Subjects meeting inclusion criteria, able to tolerate 500mg of immediate-release niacin and to provide informed consent were randomized to one of the four study groups. First experimental visit was within 12 weeks of screening visit.

Arm/Group Title	All Study Participants
Arm/Group Description	Participants received one dose of Quercetin 500 mg, Quercetin 100 mg, Quercetin 200 mg, or placebo one hour before immediate-release niacin 500 mg and underwent flushing and pharmacodymic assessments for 8 hours after Quercetin dosing. Each participant then crossed over to one of the remaining dose group/placebo in a randomized, double blind fashion after a washout period of at least 7 days. Each participant received all three doses of Quercetin and placebo.
Period Title: Quercetin 500 mg + Niacin 500 mg (1day)
STARTED	17
COMPLETED	17
NOT COMPLETED	0
Period Title: Quercetin 500 mg + Niacin 500 mg (1day)
STARTED	17
COMPLETED	17
NOT COMPLETED	0
Period Title: Quercetin 500 mg + Niacin 500 mg (1day)
STARTED	17
COMPLETED	17
NOT COMPLETED	0
Period Title: Quercetin 500 mg + Niacin 500 mg (1day)
STARTED	17
COMPLETED	17
NOT COMPLETED	0
Period Title: Quercetin 500 mg + Niacin 500 mg (1day)
STARTED	17
COMPLETED	17
NOT COMPLETED	0
Period Title: Quercetin 500 mg + Niacin 500 mg (1day)
STARTED	17
COMPLETED	17
NOT COMPLETED	0
Period Title: Quercetin 500 mg + Niacin 500 mg (1day)
STARTED	17
COMPLETED	17
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	Participants received one dose of Quercetin 500 mg, Quercetin 1000 mg, Quercetin 2000 mg, or placebo one hour before immediate-release niacin 500 mg and underwent flushing and laboratory assessment including plasma free fatty acid, beta-hydroxybutyrate and urinary eicosanoid metabolites for 8 hours after Quercetin dosing. Each participant then crossed over to the next dose group/placebo after a washout period of at least 7 days. Each participant received all three doses of Quercetin and placebo.
Overall Participants	17
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.1 (13.0)
Sex: Female, Male (Count of Participants)
Female	9 52.9%
Male	8 47.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 5.9%
Not Hispanic or Latino	16 94.1%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	7 41.2%
White	10 58.8%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Whether Quercetin Dose-dependently Reduces Laser Doppler Flux Index Primary Peak Following Immediate-release Niacin
Description	Laser Doppler flowmetry at the malar eminence measures blood flow quantitatively as red blood cell flux. Flux index is the fold-change in flux over baseline. Flux index primary peak is the maximum flux index between 0-4 hours after niacin.
Time Frame	8 hour period

Outcome Measure Data

Analysis Population Description

All subjects who finished at least one visit were analysed.

Arm/Group Title	Quercetin 500 mg	Quercetin 1000 mg	Quercetin 2000 mg	Placebo
Arm/Group Description	Participants received one dose of Quercetin 500 mg one hour before immediate-release niacin 500 mg and underwent flushing and laboratory assessment including plasma free fatty acid, beta-hydroxybutyrate and urinary eicosanoid metabolites for 8 hours after Quercetin dosing. Each participant then crossed over to the next dose group/placebo after a washout period of at least 7 days.	Participants received one dose of Quercetin 1000 mg one hour before immediate-release niacin 500 mg and underwent flushing and laboratory assessment including plasma free fatty acid, beta-hydroxybutyrate and urinary eicosanoid metabolites for 8 hours after Quercetin dosing. Each participant then crossed over to the next dose group/placebo after a washout period of at least 7 days.	Participants received one dose of Quercetin 2000 mg one hour before immediate-release niacin 500 mg and underwent flushing and laboratory assessment including plasma free fatty acid, beta-hydroxybutyrate and urinary eicosanoid metabolites for 8 hours after Quercetin dosing. Each participant then crossed over to the next dose group/placebo after a washout period of at least 7 days.	Participants received placebo one hour before immediate-release niacin 500 mg and underwent flushing and laboratory assessment including plasma free fatty acid, beta-hydroxybutyrate and urinary eicosanoid metabolites for 8 hours after Quercetin dosing. Each participant then crossed over to the next dose group/placebo after a washout period of at least 7 days.
Measure Participants	17	17	17	17
Mean (95% Confidence Interval) [Fold change over baseline]	9.9	9.4	7.7	8.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Quercetin 500 mg, Placebo
	Comments	The null hypothesis is that quercetin, at any dose, does not attenuate niacin-induced increases in dermal blood flow. Because quercetin has not been used to inhibit flushing from niacin in humans, sample size could not be determined statistically. A sample size of 8 men and 8 women was expected to allow separate estimates of effect size, variability, and shape of distribution for men and women.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Quercetin 1000 mg, Placebo
	Comments	The null hypothesis is that quercetin, at any dose, does not attenuate niacin-induced increases in dermal blood flow.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Quercetin 2000 mg, Placebo
	Comments	The null hypothesis is that quercetin, at any dose, does not attenuate niacin-induced increases in dermal blood flow.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5
	Comments
	Method	Mixed Models Analysis
	Comments

Adverse Events

Arm/Group Title	Quercetin 500 mg		Quercetin 1000 mg		Quercetin 2000 mg		Placebo
Arm/Group Description	Participants received one dose of Quercetin 500 mg one hour before immediate-release niacin 500 mg and underwent flushing and laboratory assessment including plasma free fatty acid, beta-hydroxybutyrate and urinary eicosanoid metabolites for 8 hours after Quercetin dosing. Each participant then crossed over to the next dose group/placebo after a washout period of at least 7 days.		Participants received one dose of Quercetin 1000 mg one hour before immediate-release niacin 500 mg and underwent flushing and laboratory assessment including plasma free fatty acid, beta-hydroxybutyrate and urinary eicosanoid metabolites for 8 hours after Quercetin dosing. Each participant then crossed over to the next dose group/placebo after a washout period of at least 7 days.		Participants received one dose of Quercetin 2000 mg one hour before immediate-release niacin 500 mg and underwent flushing and laboratory assessment including plasma free fatty acid, beta-hydroxybutyrate and urinary eicosanoid metabolites for 8 hours after Quercetin dosing. Each participant then crossed over to the next dose group/placebo after a washout period of at least 7 days.		Participants received placebo one hour before immediate-release niacin 500 mg and underwent flushing and laboratory assessment including plasma free fatty acid, beta-hydroxybutyrate and urinary eicosanoid metabolites for 8 hours after Quercetin dosing. Each participant then crossed over to the next dose group/placebo after a washout period of at least 7 days.
All Cause Mortality
	Quercetin 500 mg		Quercetin 1000 mg		Quercetin 2000 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Quercetin 500 mg		Quercetin 1000 mg		Quercetin 2000 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/17 (0%)		0/17 (0%)		0/17 (0%)
Other (Not Including Serious) Adverse Events
	Quercetin 500 mg		Quercetin 1000 mg		Quercetin 2000 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/17 (0%)		0/17 (0%)		0/17 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.