Niacin and Aspirin for Prostaglandin D2 Metabolism Pathways

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Vanderbilt University

Must not be taking: NSAIDs

Disqualifiers: Currently taking medication, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 7 days

10 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

Yes, you will need to stop taking your current medications, as the trial is for healthy volunteers not currently taking any medication. Additionally, you must not have used anti-inflammatory or over-the-counter pain medications for at least 2 weeks before the study.

What data supports the effectiveness of this drug?

Research shows that niacin (Vitamin B3) can increase the production of prostaglandin D2 (PGD2), which is involved in various body functions, including blood flow and inflammation. Additionally, aspirin is known to inhibit certain enzymes that produce prostaglandins, potentially balancing the effects of niacin-induced PGD2 production. ^{1 2 3 4 5}

Is the combination of niacin and aspirin generally safe for humans?

Aspirin, also known as acetylsalicylic acid, is widely used to relieve pain and reduce inflammation, but it can cause side effects like stomach upset and increased risk of bleeding. Niacin, or Vitamin B3, is generally safe but can cause flushing (a warm, red feeling in the skin) and, at high doses, liver damage. Combining these drugs may have additional effects, so it's important to consult with a healthcare provider before use. ^{6 7 8 9 10}

How does the drug niacin differ from other treatments for prostaglandin D2 metabolism pathways?

Niacin is unique because it increases the production of prostaglandin D2 (PGD2), which can cause flushing, a common side effect. This drug works by activating specific receptors and pathways that are not typically targeted by other treatments, and its effects can be modulated by combining it with aspirin or omega-3 fatty acids to reduce side effects. ^{2 4 11 12 13}

What is the purpose of this trial?

This trial uses niacin and aspirin to study their effects on a body chemical in healthy volunteers. Researchers measure chemicals in urine and blood to understand how this chemical is broken down.

Research Team

Claus M Schneider, PhD

Principal Investigator

Vanderbilt University

Eligibility Criteria

This trial is for healthy volunteers who aren't on any medications. It's not open to those who've taken anti-inflammatory or over-the-counter pain meds like NSAIDs in the two weeks before the study starts.

Inclusion Criteria

I am healthy and not on any medications.

Exclusion Criteria

I have used over-the-counter pain or anti-inflammatory medications within the last 2 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive niacin and aspirin treatments, with urine and blood samples collected at specified intervals

7 days

Daily visits for aspirin administration, followed by a visit for niacin administration and sample collection

Monitoring

Participants are monitored for prostaglandin metabolites in urine and blood over a 10-hour period post-treatment

10 hours

Continuous monitoring and sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Treatment Details

Interventions

• Aspirin
• Niacin
• PGD2

Trial Overview The study is looking into a potential new pathway between two prostaglandins by giving participants niacin, PGD2, and aspirin to see how these substances affect prostaglandin metabolism.

Participant Groups

Group I: niacin + regular-strength aspirin Experimental Treatment 2 Interventions

Volunteers will provide a urine sample. They will receive 7 tablets of regular-strength aspirin (325 mg) and be instructed to take one tablet daily for 7 days. On the seventh day, they return to have blood drawn, urine collected, and receive niacin as described in arm 1.

Group II: niacin + low-dose aspirin Experimental Treatment 2 Interventions

Volunteers will provide a urine sample. They will receive 7 tablets of low-dose aspirin (81 mg) and be instructed to take one tablet daily for 7 days. On the seventh day, they return to have blood drawn, urine collected, and receive niacin as described in arm 1.

Group III: niacin Experimental Treatment 1 Intervention

Blood (10 ml) will be drawn from the subject. Immediately before or after the blood draw the subject will collect a urine (3-10 ml) sample. After the baseline blood draw and the urine sample is collected the subject will take 500 mg of niacin. The niacin will not be an extended release formulation. Subjects will be encouraged to drink plenty of water during the study. Subjects are instructed to collect urine 1, 2, 4, 6, 8, and 10 hours after niacin administration. Subjects will collect their urine in separate plastic tubes that will be provided to them. Approximately 1-2 h after niacin administration a second blood sample (10 ml) will be drawn from the subject.

Group IV: deuterated PGD2 Experimental Treatment 1 Intervention

Volunteers will come to the clinical research center. Volunteers will provide a urine sample. The volunteers will be fitted to record an electrocardiogram (ECG) and blood pressure. ECG will be recorded continuously. Blood pressure will be taken at baseline and every 10 minutes thereafter for one hour. The solution with deuterated PGD2 (10 microgram) will be infused over the course of 30 min. Volunteers will be monitored for 1 h after the end of the infusion, and volunteers will start collecting urine in intervals up to 10 h. Infusion of the deuterated PGD2 solution will be performed in the presence of a physician. The injection solution will be prepared by Vanderbilt University Medical Center (VUMC) Investigational Drug Services. The solution will be sterile and pyrogen free.

Who Is Running the Clinical Trial?

Vanderbilt University

Lead Sponsor

Trials

714

Recruited

6,143,000+

Vanderbilt University Medical Center

Collaborator

Trials

922

Recruited

939,000+

References

1. United States pubmed.ncbi.nlm.nih.gov

Quantification of the major urinary metabolite of prostaglandin D2 by a stable isotope dilution mass spectrometric assay. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

High dietary niacin may increase prostaglandin formation but does not increase tumor formation in ApcMin/+ mice. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Opposing roles of PGD2 in GBM. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Release of markedly increased quantities of prostaglandin D2 in vivo in humans following the administration of nicotinic acid. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Tetranor PGDM, an abundant urinary metabolite reflects biosynthesis of prostaglandin D2 in mice and humans. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Druggable Prostanoid Pathway. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Differential inhibition of prostaglandin endoperoxide synthase (cyclooxygenase) isozymes by aspirin and other non-steroidal anti-inflammatory drugs. [2022]

8. Ireland pubmed.ncbi.nlm.nih.gov

In vivo impact of prodrug isosorbide-5-nicotinate-2-aspirinate on lipids and prostaglandin D2: is this a new immediate-release therapeutic option for niacin? [2015]

9. United States pubmed.ncbi.nlm.nih.gov

Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunities. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Prostaglandin and thromboxane biosynthesis. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Niacin and biosynthesis of PGD₂by platelet COX-1 in mice and humans. [2021]

12. New Zealand pubmed.ncbi.nlm.nih.gov

Attenuation of niacin-induced prostaglandin D(2) generation by omega-3 fatty acids in THP-1 macrophages and Langerhans dendritic cells. [2021]

13. Ireland pubmed.ncbi.nlm.nih.gov

Nicotinic acid induces secretion of prostaglandin D2 in human macrophages: an in vitro model of the niacin flush. [2018]