Alternative Options to Minimize Niacin-Induced Flushing

• Sponsor: Patrick Moriarty, MD, FACP, FACC (Other)
• Overall Status: Completed
• CT.gov ID: NCT00895193
• Collaborator: (none)
• Enrollment: 100
• Location: 1
• Arms: 4
• Duration (Months): 23
• Patients Per Site Per Month: 4.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hypercholesterolemia; Flushing	Other: Apple pectin; Drug: Aspirin 325 mg; Other: Placebo	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Supportive Care
• Official Title: Alternative Options to Minimize Niacin-Induced Flushing
• Study Start Date: Jan 1, 2009
• Actual Primary Completion Date: Dec 1, 2010
• Actual Study Completion Date: Dec 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Apple-pectin 2000mg Participant receives Apple pectin 2000mg 30 minutes prior to a one-time 1000mg dose of extended-release niacin.	Other: Apple pectin; Apple pectin 2000mg
Active Comparator: Regular Non-enteric coated aspirin 325mg Participant receives aspirin 325 mg 30 minutes prior to a one-time 1000mg dose of extended-release niacin.	Drug: Aspirin 325 mg; Aspirin 325 mg
Active Comparator: 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.	Other: Apple pectin; Apple pectin 2000mg; Drug: Aspirin 325 mg; Aspirin 325 mg
Placebo Comparator: Placebo Comparator Participant receives placebo 30 minutes prior to a one-time 1000mg dose of extended-release niacin.	Other: Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Kansas Medical Center	Kansas City	Kansas	United States	66160

Sponsors and Collaborators

• Patrick Moriarty, MD, FACP, FACC

Investigators

• Principal Investigator: Patrick Moriarty, MD, University of Kansas Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Patrick Moriarty, MD, FACP, FACC, Director, Clinical Pharmacology, University of Kansas Medical Center
• ClinicalTrials.gov Identifier: NCT00895193
• Other Study ID Numbers: 11627
• First Posted: May 8, 2009
• Last Update Posted: Jun 5, 2014
• Last Verified: May 1, 2014

• Keywords provided by Patrick Moriarty, MD, FACP, FACC, Director, Clinical Pharmacology, University of Kansas Medical Center: Niacin; Hypercholesterolemia; Flushing
• Additional relevant MeSH terms: Hypercholesterolemia; Flushing; Aspirin

Study Results

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.

Arm/Group Title	Apple-pectin 2000mg	Regular Non-enteric Coated Aspirin 325mg	Apple Pectin + Aspirin	Placebo Comparator
Arm/Group Description	Participant receives Apple pectin 2000mg 30 minutes prior to a one-time 1000mg dose of extended-release niacin.	Participant receives aspirin 325 mg 30 minutes prior to a one-time 1000mg dose of extended-release niacin.	Participant receives apple pectin 2000mg and aspirin 325 mg 30 minutes prior to a one-time 1000mg dose of extended-release niacin.	Participant receives placebo 30 minutes prior to a one-time 1000mg dose of extended-release niacin.
Period Title: Overall Study
STARTED	25	25	25	25
COMPLETED	25	25	25	25
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Apple-pectin 2000mg	Regular Non-enteric Coated Aspirin 325mg	Apple Pectin + Aspirin	Placebo Comparator	Total
Arm/Group Description	Participant receives Apple pectin 2000mg 30 minutes prior to a one-time 1000mg dose of extended-release niacin.	Participant receives aspirin 325 mg 30 minutes prior to a one-time 1000mg dose of extended-release niacin.	Participant receives apple pectin 2000mg and aspirin 325 mg 30 minutes prior to a one-time 1000mg dose of extended-release niacin.	Participant receives placebo 30 minutes prior to a one-time 1000mg dose of extended-release niacin.	Total of all reporting groups
Overall Participants	25	25	25	25	100
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34 (11.5)	40 (13.3)	40 (12.3)	38 (12.7)	38.2 (12.5)
Sex: Female, Male (Count of Participants)
Female	11 44%	12 48%	11 44%	11 44%	45 45%
Male	14 56%	13 52%	14 56%	14 56%	55 55%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	4 16%	9 36%	5 20%	5 20%	23 23%
White	16 64%	15 60%	20 80%	20 80%	71 71%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	5 20%	1 4%	0 0%	0 0%	6 6%
Region of Enrollment (participants) [Number]
United States	25 100%	25 100%	25 100%	25 100%	100 100%
Body Mass Index (kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m2]	26 (5.5)	27 (6.2)	26 (5.3)	26 (5.0)	26.4 (5.4)
Waist Circumference (inches) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [inches]	35 (6.1)	36 (6.3)	34 (5.0)	35 (5.3)	35 (5.65)

Outcome Measures

1. Primary Outcome

Title	Incidence of Flushing
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Apple-pectin 2000mg	Regular Non-enteric Coated Aspirin 325mg	Apple Pectin + Aspirin	Placebo Comparator
Arm/Group Description	Participant receives Apple pectin 2000mg 30 minutes prior to a one-time 1000mg dose of extended-release niacin.	Participant receives aspirin 325 mg 30 minutes prior to a one-time 1000mg dose of extended-release niacin.	Participant receives apple pectin 2000mg and aspirin 325 mg 30 minutes prior to a one-time 1000mg dose of extended-release niacin.	Participant receives placebo 30 minutes prior to a one-time 1000mg dose of extended-release niacin.
Measure Participants	25	25	25	25
Number [participants]	22 88%	18 72%	20 80%	23 92%

2. Primary Outcome

Title	Time to Flushing
Description	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

Outcome Measure Data

Analysis Population Description

All participants randomized to the study completed the study. Each arm had 25 participants.

Arm/Group Title	Apple-pectin 2000mg	Regular Non-enteric Coated Aspirin 325mg	Apple Pectin + Aspirin	Placebo Comparator
Arm/Group Description	Participant receives Apple pectin 2000mg 30 minutes prior to a one-time 1000mg dose of extended-release niacin.	Participant receives aspirin 325 mg 30 minutes prior to a one-time 1000mg dose of extended-release niacin.	Participant receives apple pectin 2000mg and aspirin 325 mg 30 minutes prior to a one-time 1000mg dose of extended-release niacin.	Participant receives placebo 30 minutes prior to a one-time 1000mg dose of extended-release niacin.
Measure Participants	25	25	25	25
Mean (Standard Deviation) [minutes]	75.4 (51.7)	48.7 (33.8)	58.8 (42.5)	58.1 (66.2)

3. Primary Outcome

Title	Duration of Flushing
Description	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

Outcome Measure Data

Analysis Population Description

All participants randomized to the study completed the study. Each arm had 25 participants.

Arm/Group Title	Apple-pectin 2000mg	Regular Non-enteric Coated Aspirin 325mg	Apple Pectin + Aspirin	Placebo Comparator
Arm/Group Description	Participant receives Apple pectin 2000mg 30 minutes prior to a one-time 1000mg dose of extended-release niacin.	Participant receives aspirin 325 mg 30 minutes prior to a one-time 1000mg dose of extended-release niacin.	Participant receives apple pectin 2000mg and aspirin 325 mg 30 minutes prior to a one-time 1000mg dose of extended-release niacin.	Participant receives placebo 30 minutes prior to a one-time 1000mg dose of extended-release niacin.
Measure Participants	25	25	25	25
Mean (Standard Deviation) [minutes]	43.3 (35.7)	52.7 (53.5)	58.3 (40.2)	88 (66)

4. Primary Outcome

Title	Maximum Flushing Severity Score
Description	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

Outcome Measure Data

Analysis Population Description

All participants randomized to the study completed the study. Each arm had 25 participants.

Arm/Group Title	Apple-pectin 2000mg	Regular Non-enteric Coated Aspirin 325mg	Apple Pectin + Aspirin	Placebo Comparator
Arm/Group Description	Participant receives Apple pectin 2000mg 30 minutes prior to a one-time 1000mg dose of extended-release niacin.	Participant receives aspirin 325 mg 30 minutes prior to a one-time 1000mg dose of extended-release niacin.	Participant receives apple pectin 2000mg and aspirin 325 mg 30 minutes prior to a one-time 1000mg dose of extended-release niacin.	Participant receives placebo 30 minutes prior to a one-time 1000mg dose of extended-release niacin.
Measure Participants	25	25	25	25
Mean (Standard Deviation) [units on a scale]	3.2 (2.7)	2.8 (2.6)	3.3 (2.5)	3.6 (2.6)

Adverse Events

Arm/Group Title	Apple-pectin 2000mg		Regular Non-enteric Coated Aspirin 325mg		Apple Pectin + Aspirin		Placebo Comparator
Arm/Group Description	Participant receives Apple pectin 2000mg 30 minutes prior to a one-time 1000mg dose of extended-release niacin.		Participant receives aspirin 325 mg 30 minutes prior to a one-time 1000mg dose of extended-release niacin.		Participant receives apple pectin 2000mg and aspirin 325 mg 30 minutes prior to a one-time 1000mg dose of extended-release niacin.		Participant receives placebo 30 minutes prior to a one-time 1000mg dose of extended-release niacin.
All Cause Mortality
	Apple-pectin 2000mg		Regular Non-enteric Coated Aspirin 325mg		Apple Pectin + Aspirin		Placebo Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Apple-pectin 2000mg		Regular Non-enteric Coated Aspirin 325mg		Apple Pectin + Aspirin		Placebo Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/25 (0%)		0/25 (0%)		0/25 (0%)
Other (Not Including Serious) Adverse Events
	Apple-pectin 2000mg		Regular Non-enteric Coated Aspirin 325mg		Apple Pectin + Aspirin		Placebo Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/25 (0%)		0/25 (0%)		0/25 (0%)

Limitations/Caveats

Limitations include: pilot design, small sample size, short duration of a one-time niacin dose, utilization of only one niacin formulation.

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.