Flushing, Hypercholesterolemia
Conditions
Keywords
Niacin, Hypercholesterolemia, Flushing
Brief summary
Niacin (Vitamin B3) is known to effectively and safely treat hypercholesterolemia. However, use of niacin is limited due to incidents of flushing which limits its acceptability. Some information suggests that applesauce can reduce the incidence and severity of flushing. The apple pectin in particular is thought to be the ingredient that affects this reaction. To determine if the apple pectin does affect flushing from niacin, the investigators will study the affects of isolated apple pectin in pill form. The investigators plan on recruiting 100 patients, and giving them 1000 mg of Niacin to induce flushing. Patients will be divided into 4 treatment groups and receive either pectin, aspirin, a combination of both, or placebo. Incidents and severity of flushing will be monitored for up to 6 hours post Niacin ingestion.
Interventions
OTHERApple pectin
Apple pectin 2000mg
DRUGAspirin 325 mg
Aspirin 325 mg
OTHERPlacebo
Placebo
Sponsors
Patrick Moriarty, MD, FACP, FACC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* An adult between 21 and 70 years of age. * Male or female (If female must be postmenopausal for at least 1 year, surgically sterile or using an effective form of contraception). * Able to speak and read English. * Willing to comply with study specific instructions, and complete all study procedures according to protocol. * Able to understand study rationale and sign informed consent.
Exclusion criteria
* Females of child-bearing potential not using acceptable method of contraception and perimenopausal females. * History of gout * History of diabetes mellitus * History of coronary heart disease * History of, or currently experiencing, renal disease including, but not limited to, renal insufficiency, nephrolithiasis or chronic renal failure. * History of, or currently experiencing, major chronic gastrointestinal condition including gallbladder disease, liver disease and peptic ulcer disease * Known sensitivity to niacin, Aspirin or nonsteroidal anti-inflammatory agents (NSAIDs) * History of migraine or cluster headaches * Currently using antihistamines, aspirin or NSAIDS on a consistent basis * Presence or history of any medical or psychosocial condition that, in the opinion of the investigator, would limit the patient's successful participation or would compromise the patient's safe participation. * Lab abnormalities at screening, including but not limited to elevated liver enzymes or blood sugar levels that might indicate additional risk to the patient's continued participation. * Currently taking medication that might be contraindicated with the study drug or Niacin or study procedures (including Niacin, lipid-lowering drugs, chronic aspirin or laxative use). * Clinically significant finding from physical exam that would affect the patient's safe participation or completion of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Flushing | Hourly for 6 hours on day of dosing | Flushing assessment performed hourly for 6 hours after niacin administration. Incidence of flushing based on if the participant experience any niacin-induced flushing during the 6 hour period after dosing. Represents # of participants that experienced event. |
| Time to Flushing | 6 hours after dosing | The time it took, in minutes, for a participant to experience any flushing. Time to flush for individuals that did not experience flushing within 6 hours was set to 360 minutes. |
| Duration of Flushing | 6 hours after dosing | The amount of time, in minutes, that flushing lasted. Duration of individuals without experience flushing within 6 hours was set to 0 minutes. |
| Maximum Flushing Severity Score | 6 hours after dosing | Flushing assessment performed hourly for six hours. Assessment of severity done using the validated visual analog scale (VAS) flushing assessment tool (FAST). Severity rated using a VAS from mild (1-3), moderate (4-6), severe (7-9) to very severe (10). The maximum severity score was the maximum severity score of each individual during the 6 hours of monitoring time period. |
Countries
United States
Participant flow
Recruitment details
Initial screening occurred over the telephone. Subjects that met preliminary study criteria were scheduled for a screening visit. Recruitment was conducted at the University of Kansas Medical Center.
Participants by arm
| Arm | Count |
|---|---|
| Apple-pectin 2000mg Participant receives Apple pectin 2000mg 30 minutes prior to a one-time 1000mg dose of extended-release niacin. | 25 |
| Regular Non-enteric Coated Aspirin 325mg Participant receives aspirin 325 mg 30 minutes prior to a one-time 1000mg dose of extended-release niacin. | 25 |
| Apple Pectin + Aspirin Participant receives apple pectin 2000mg and aspirin 325 mg 30 minutes prior to a one-time 1000mg dose of extended-release niacin. | 25 |
| Placebo Comparator Participant receives placebo 30 minutes prior to a one-time 1000mg dose of extended-release niacin. | 25 |
| Total | 100 |
Baseline characteristics
| Characteristic | Apple-pectin 2000mg | Regular Non-enteric Coated Aspirin 325mg | Apple Pectin + Aspirin | Placebo Comparator | Total |
|---|---|---|---|---|---|
| Age, Continuous | 34 years STANDARD_DEVIATION 11.5 | 40 years STANDARD_DEVIATION 13.3 | 40 years STANDARD_DEVIATION 12.3 | 38 years STANDARD_DEVIATION 12.7 | 38.2 years STANDARD_DEVIATION 12.5 |
| Body Mass Index | 26 kg/m2 STANDARD_DEVIATION 5.5 | 27 kg/m2 STANDARD_DEVIATION 6.2 | 26 kg/m2 STANDARD_DEVIATION 5.3 | 26 kg/m2 STANDARD_DEVIATION 5 | 26.4 kg/m2 STANDARD_DEVIATION 5.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 9 Participants | 5 Participants | 5 Participants | 23 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 1 Participants | 0 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) White | 16 Participants | 15 Participants | 20 Participants | 20 Participants | 71 Participants |
| Region of Enrollment United States | 25 participants | 25 participants | 25 participants | 25 participants | 100 participants |
| Sex: Female, Male Female | 11 Participants | 12 Participants | 11 Participants | 11 Participants | 45 Participants |
| Sex: Female, Male Male | 14 Participants | 13 Participants | 14 Participants | 14 Participants | 55 Participants |
| Waist Circumference | 35 inches STANDARD_DEVIATION 6.1 | 36 inches STANDARD_DEVIATION 6.3 | 34 inches STANDARD_DEVIATION 5 | 35 inches STANDARD_DEVIATION 5.3 | 35 inches STANDARD_DEVIATION 5.65 |
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 / 25 | 0 / 25 | 0 / 25 | 0 / 25 |
| serious Total, serious adverse events | 0 / 25 | 0 / 25 | 0 / 25 | 0 / 25 |
Outcome results
Primary
Duration of Flushing
The amount of time, in minutes, that flushing lasted. Duration of individuals without experience flushing within 6 hours was set to 0 minutes.
Time frame: 6 hours after dosing
Population: All participants randomized to the study completed the study. Each arm had 25 participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Apple-pectin 2000mg | Duration of Flushing | 43.3 minutes | Standard Deviation 35.7 |
| Regular Non-enteric Coated Aspirin 325mg | Duration of Flushing | 52.7 minutes | Standard Deviation 53.5 |
| Apple Pectin + Aspirin | Duration of Flushing | 58.3 minutes | Standard Deviation 40.2 |
| Placebo Comparator | Duration of Flushing | 88 minutes | Standard Deviation 66 |
Primary
Incidence of Flushing
Flushing assessment performed hourly for 6 hours after niacin administration. Incidence of flushing based on if the participant experience any niacin-induced flushing during the 6 hour period after dosing. Represents # of participants that experienced event.
Time frame: Hourly for 6 hours on day of dosing
Population: This was a single-site, randomized trial, 4-arm parallel design trial. Each arm consisted of 25 randomized participants. All participants completed the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apple-pectin 2000mg | Incidence of Flushing | 22 participants |
| Regular Non-enteric Coated Aspirin 325mg | Incidence of Flushing | 18 participants |
| Apple Pectin + Aspirin | Incidence of Flushing | 20 participants |
| Placebo Comparator | Incidence of Flushing | 23 participants |
Primary
Maximum Flushing Severity Score
Flushing assessment performed hourly for six hours. Assessment of severity done using the validated visual analog scale (VAS) flushing assessment tool (FAST). Severity rated using a VAS from mild (1-3), moderate (4-6), severe (7-9) to very severe (10). The maximum severity score was the maximum severity score of each individual during the 6 hours of monitoring time period.
Time frame: 6 hours after dosing
Population: All participants randomized to the study completed the study. Each arm had 25 participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Apple-pectin 2000mg | Maximum Flushing Severity Score | 3.2 units on a scale | Standard Deviation 2.7 |
| Regular Non-enteric Coated Aspirin 325mg | Maximum Flushing Severity Score | 2.8 units on a scale | Standard Deviation 2.6 |
| Apple Pectin + Aspirin | Maximum Flushing Severity Score | 3.3 units on a scale | Standard Deviation 2.5 |
| Placebo Comparator | Maximum Flushing Severity Score | 3.6 units on a scale | Standard Deviation 2.6 |
Primary
Time to Flushing
The time it took, in minutes, for a participant to experience any flushing. Time to flush for individuals that did not experience flushing within 6 hours was set to 360 minutes.
Time frame: 6 hours after dosing
Population: All participants randomized to the study completed the study. Each arm had 25 participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Apple-pectin 2000mg | Time to Flushing | 75.4 minutes | Standard Deviation 51.7 |
| Regular Non-enteric Coated Aspirin 325mg | Time to Flushing | 48.7 minutes | Standard Deviation 33.8 |
| Apple Pectin + Aspirin | Time to Flushing | 58.8 minutes | Standard Deviation 42.5 |
| Placebo Comparator | Time to Flushing | 58.1 minutes | Standard Deviation 66.2 |