Flushing
Conditions
Keywords
Skin, pharmacology, metabolism, lipid
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.
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.
Interventions
DIETARY_SUPPLEMENTQuercetin
Quercetin 500, 1000, or 2000 mg PO one time
DIETARY_SUPPLEMENTPlacebo
Placebo PO one time
Sponsors
Abbott
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 75 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants 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. | 17 |
| Total | 17 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 38.1 years STANDARD_DEVIATION 13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 17 | 0 / 17 | 0 / 17 | 0 / 17 |
| serious Total, serious adverse events | 0 / 17 | 0 / 17 | 0 / 17 | 0 / 17 |
Outcome results
Primary
Whether Quercetin Dose-dependently Reduces Laser Doppler Flux Index Primary Peak Following Immediate-release Niacin
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
Population: All subjects who finished at least one visit were analysed.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Quercetin 500 mg | Whether Quercetin Dose-dependently Reduces Laser Doppler Flux Index Primary Peak Following Immediate-release Niacin | 9.9 Fold change over baseline |
| Quercetin 1000 mg | Whether Quercetin Dose-dependently Reduces Laser Doppler Flux Index Primary Peak Following Immediate-release Niacin | 9.4 Fold change over baseline |
| Quercetin 2000 mg | Whether Quercetin Dose-dependently Reduces Laser Doppler Flux Index Primary Peak Following Immediate-release Niacin | 7.7 Fold change over baseline |
| Placebo | Whether Quercetin Dose-dependently Reduces Laser Doppler Flux Index Primary Peak Following Immediate-release Niacin | 8.9 Fold change over baseline |
Comparison: 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.p-value: 0.5Mixed Models Analysis
Comparison: The null hypothesis is that quercetin, at any dose, does not attenuate niacin-induced increases in dermal blood flow.p-value: 0.8Mixed Models Analysis
Comparison: The null hypothesis is that quercetin, at any dose, does not attenuate niacin-induced increases in dermal blood flow.p-value: 0.5Mixed Models Analysis