Biosynthesis of PGD2 in Vivo
Study Details
Study Description
Brief Summary
The investigator would like to see if aspirin could block niacin-induced flushing by analyzing blood and urine after taking aspirin.
Phase I: Subjects were assigned to either placebo or aspirin groups. They were given 5 days of 81 mg aspirin or placebo. On day 5, they were given a single dose of niacin (600 mg) administered 30 minutes after the last dose of aspirin or placebo. The same subjects came back for cross-over study and were assigned to a different group. There was a 2-week washout period between each treatment. Urine was collected sequentially for analysis
Phase II: The same study subjects come back for an open label one week study. They were given 5 days of taking 81 mg Aspirin, taken once daily, followed by a single dose of 600 mg Niacin on day 6. Urine was collected sequentially for analysis
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
The purpose of this study is to look at the roles of various blood cells and their contributions of different prostaglandins. The intention is that by better understanding these prostaglandins and various metabolites, it will provide insights into their roles in the cardiovascular system.
Prostaglandins and metabolites are naturally occurring substances found in the blood and urine which can act as markers which can be quantified and studied as we will be doing in this study. Flushing response to niacin will also be assessed by laser doppler measuring blood flow of the facial skin.
Untransformed and transformed data will be subjected to exploratory analysis of variance appropriated for a three factor design with one two period crossover factor and two non-repeated factors. Additionally, volunteer's test(s) for paired observations will characterize the magnitude of the niacin effect on the response variables within selected time points.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo phase I Subjects were given 5 days of placebo. On day 5, they were given a single dose of niacin (600 mg) administered 30 minutes after the last dose of placebo. Urine was collected sequentially for analysis. The same subjects came back for cross-over study and were assigned to Aspirin group. There was a 2-week washout period between each treatment. |
Drug: Placebo
Drug: Niacin
Other Names:
|
| Active Comparator: Aspirin phase I Subjects were given 5 days of 81 mg aspirin. On day 5, they were given a single dose of niacin (600 mg) administered 30 minutes after the last dose of aspirin or placebo. Urine was collected sequentially for analysis. |
Drug: Aspirin
Other Names:
Drug: Niacin
Other Names:
|
| Active Comparator: Aspirin phase II In phase II study, subjects were given 5 days of 81 mg aspirin. On day 6, they were given a single dose of niacin (600 mg) administered 24 hours after the last dose of aspirin. Urine was collected sequentially for analysis |
Drug: Aspirin
Other Names:
Drug: Niacin
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Percentage Change of Area Under Curve for the Urinary Prostaglandins Concentration Versus Time Curve (AUC) in Response to Aspirin or Placebo [-2-0, 0-2, 2-4, 4-6, 6-12 and 12-24 hours pre or post niacin]
Percentage change of area under the urinary prostaglandins concentration versus time curve (AUC) in response to niacin with or without pretreatment of aspirin was studied. This outcome measures whether aspirin instead of placebo will impact the subjects' response to niacin. The area was normalized by percentile.
Eligibility Criteria
Criteria
Inclusion Criteria:
age between 18-70
-
subject must be in good health as based on medical history
-
All subjects must be non-smoking, non-pregnant volunteers
-
Female subjects of child bearing potential must be using a medically acceptable method of contraception throughout the entire study period. All female subjects must consent to a urine pregnancy test at screening and just prior to the start of each treatment period of the study, which must be negative at all time points.
Exclusion Criteria:
-
subjects with any medical condition that according to the investigator may interfere with interpretation of the study results, be indicative of an underlying disease state, or compromise the safety of a potential subject.
-
subjects who have received an experimental drug within 30 days prior to the study.
-
subjects who have taken medications at least 10 days prior to the study. Birth Control pills are acceptable and shall not be excluded.
-
Subjects who have taken aspirin or aspirin containing products for at least 10 days prior to the study.
-
Subjects who have taken acetaminophen, NSAIDS, COX-2 inhibitors (OTC or prescription) for at least 10 days prior to the study.
-
Subjects who are currently consuming any type of tobacco product(s).
-
Subjects who consume high doses of antioxidant vitamins daily (vitamin C > 1000mg, Vitamin E > 400 IU, Beta Carotene > 1000IU, Vitamin A > 5000IU, Selenium > 200mcg, Folic Acid > 1mg) for the 2 weeks prior to the start of the study and throughout the study.
-
Subjects who consume alcohol, caffeine or high fat food 24 hours prior to study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Pennsylvania Hospital | Philadelphia | Pennsylvania | United States | 19104 |
Sponsors and Collaborators
- University of Pennsylvania
Investigators
- Principal Investigator: Wenliang Song, MD, University of Pennsylvania
- Study Chair: Garret FitzGerald, MD, University of Pennsylvania
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 806115 - FitzGerald, MD
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | "Placebo+Niacin First, Then Aspirin+Niacin | Aspirin+Niacin First, Then Placebo+Niacin |
|---|---|---|
| Arm/Group Description | Phase I: Subjects were assigned to either placebo or aspirin groups. They were given 5 days of 81 mg aspirin or placebo. On day 5, they were given a single dose of niacin (600 mg) administered 30 minutes after the last dose of aspirin or placebo. The same subjects came back for cross-over study and were assigned to a different group. There was a 2-week washout period between each treatment. Urine was collected sequentially for analysis Phase II: The same study subjects come back for an open label one week study. They were given 5 days of taking 81 mg Aspirin, taken once daily, followed by a single dose of 600 mg Niacin on day 6. Urine was collected sequentially for analysis | Phase I: Subjects were assigned to either placebo or aspirin groups. They were given 5 days of 81 mg aspirin or placebo. On day 5, they were given a single dose of niacin (600 mg) administered 30 minutes after the last dose of aspirin or placebo. The same subjects came back for cross-over study and were assigned to a different group. There was a 2-week washout period between each treatment. Urine was collected sequentially for analysis Phase II: The same study subjects come back for an open label one week study. They were given 5 days of taking 81 mg Aspirin, taken once daily, followed by a single dose of 600 mg Niacin on day 6. Urine was collected sequentially for analysis |
| Period Title: 1st Intervention (5 Days) | ||
| STARTED | 5 | 4 |
| COMPLETED | 5 | 4 |
| NOT COMPLETED | 0 | 0 |
| Period Title: 1st Intervention (5 Days) | ||
| STARTED | 5 | 4 |
| COMPLETED | 5 | 4 |
| NOT COMPLETED | 0 | 0 |
| Period Title: 1st Intervention (5 Days) | ||
| STARTED | 5 | 4 |
| COMPLETED | 5 | 4 |
| NOT COMPLETED | 0 | 0 |
| Period Title: 1st Intervention (5 Days) | ||
| STARTED | 5 | 4 |
| COMPLETED | 5 | 4 |
| NOT COMPLETED | 0 | 0 |
| Period Title: 1st Intervention (5 Days) | ||
| STARTED | 5 | 4 |
| COMPLETED | 5 | 4 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | All Study Participants |
|---|---|
| Arm/Group Description | All participants had the same experience of interventions throughout the study, just in different randomized orders of receipt. |
| Overall Participants | 9 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
9
100%
|
| >=65 years |
0
0%
|
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
34
(3)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
4
44.4%
|
| Male |
5
55.6%
|
| Region of Enrollment (participants) [Number] | |
| United States |
9
100%
|
Outcome Measures
| Title | Percentage Change of Area Under Curve for the Urinary Prostaglandins Concentration Versus Time Curve (AUC) in Response to Aspirin or Placebo |
|---|---|
| Description | Percentage change of area under the urinary prostaglandins concentration versus time curve (AUC) in response to niacin with or without pretreatment of aspirin was studied. This outcome measures whether aspirin instead of placebo will impact the subjects' response to niacin. The area was normalized by percentile. |
| Time Frame | -2-0, 0-2, 2-4, 4-6, 6-12 and 12-24 hours pre or post niacin |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Placebo | Aspirin |
|---|---|---|
| Arm/Group Description | ||
| Measure Participants | 9 | 9 |
| Mean (95% Confidence Interval) [Percentage change of area under curve] |
95
|
43
|
Adverse Events
| Time Frame | 8 weeks | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | P1: Placebo/Aspirin Followed by Niacin | P2: Aspirin and Niacin | ||
| Arm/Group Description | Phase 1, 5 days of placebo, followed by a single dose of 600mg niacin on day 6, 10 day washout and 5 days of aspirin 81 mg x followed by a single dose of 600 mg niacin on day 6 P1, placebo/aspirin followed by niacin: 5 days of placebo or aspirin followed by 600 mg niacin, 10 day washout in between two 6-day study periods | Phase 2, aspirin 81 mg x 5 days and a single dose of 600 mg niacin on day 6 P2, aspirin and niacin: aspirin 81 mg x 5 days and a single dose niacin on day 6 | ||
All Cause Mortality |
||||
| P1: Placebo/Aspirin Followed by Niacin | P2: Aspirin and Niacin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/9 (0%) | 0/9 (0%) | ||
Serious Adverse Events |
||||
| P1: Placebo/Aspirin Followed by Niacin | P2: Aspirin and Niacin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/9 (0%) | 0/9 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| P1: Placebo/Aspirin Followed by Niacin | P2: Aspirin and Niacin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/9 (0%) | 0/9 (0%) | ||
Limitations/Caveats
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 | Wenliang Song, MD |
|---|---|
| Organization | Upenn |
| Phone | 215-662-4652. |
| wenliangsong@gmail.com |
- 806115 - FitzGerald, MD