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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new metabolic pathway involving prostaglandin D2, a compound related to inflammation and blood flow. Researchers aim to determine if it leads to another compound, 11-dehydro-thromboxane B2, potentially revealing new insights into the body's handling of inflammation. Participants will try different combinations of niacin (a B vitamin) and aspirin, with some receiving an infusion of a special form of prostaglandin D2. This trial targets healthy individuals not taking any medications, especially those who haven't recently used pain relievers like NSAIDs. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a unique opportunity to contribute to groundbreaking scientific discovery.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that niacin, or Vitamin B3, is generally safe but can cause some side effects. The most common side effect is flushing, a warm, red sensation on the skin due to increased blood flow. While niacin can help lower cholesterol, high doses might harm the liver.

Studies have found that taking niacin with aspirin may reduce flushing. Aspirin, a common over-the-counter pain reliever, is generally safe for most people in regular doses, though it can cause stomach upset or bleeding problems in some individuals.

Limited information exists on the safety of prostaglandin D2 (PGD2) in humans as a treatment. This trial is in its early phase, focusing on understanding how the treatment works in the body rather than its long-term safety. At this stage, researchers test the treatment on a small number of people to check for any immediate side effects.

Researchers will closely monitor participants for any adverse effects to ensure their safety during the study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments in this trial because they explore how niacin and aspirin might influence prostaglandin D2 (PGD2) metabolism, which is a fresh approach compared to standard treatments for inflammation-related conditions. Standard treatments often focus on blocking inflammation directly, but these investigational treatments aim to modulate the PGD2 pathway, which is involved in various bodily processes, including inflammation and vasodilation. The use of deuterated PGD2 is particularly unique, as it allows for a more precise study of the metabolic pathways. Additionally, combining niacin with different dosages of aspirin could offer insights into optimizing anti-inflammatory effects while minimizing side effects. This novel approach could potentially lead to more targeted therapies with improved safety profiles.

What evidence suggests that this trial's treatments could be effective for prostaglandin metabolism pathways?

This trial will examine the effects of niacin and aspirin on prostaglandin D2 (PGD2) metabolism pathways. Studies have shown that niacin (Vitamin B3) can increase PGD2 production, which helps regulate blood flow. Niacin is well-known for treating high cholesterol and reducing heart disease risk. However, it can cause flushing, a temporary redness of the skin, due to PGD2 release. In this trial, some participants will receive niacin alone, while others will receive niacin with either low-dose or regular-strength aspirin. Research suggests that aspirin with niacin may reduce flushing by lowering PGD2 levels. Additionally, niacin has been found to help with ulcerative colitis, a type of bowel disease, by affecting the PGD2 pathway. Overall, niacin's interactions with prostaglandins show promise in various areas. ^{3 4 6 7 8}

Who Is on the Research Team?

Claus M Schneider, PhD

Principal Investigator

Vanderbilt University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3224853/

High dietary niacin may increase prostaglandin formation ... High doses of niacin (nicotinic acid) used to treat dyslipidemias cause flushing, due to high levels of prostaglandin D2 (PGD2).

2. ods.od.nih.gov ods.od.nih.gov/factsheets/Niacin-HealthProfessional/

Niacin - Health Professional Fact Sheet Niacin (Vit B3) overview for health professionals. Research health effects, dosing, sources, deficiency symptoms, side effects, and interactions here.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0003986124002856

Niacin-induced flushing: Mechanism, pathophysiology, and ... In addition to its vasodilator effects, niacin cures a wide range of lipid irregularities in persons with mixed dyslipidemia. Along with its hypolipidemic ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S095528631630331X

Exogenous fatty acids and niacin on acute prostaglandin ... Niacin (also commonly known as nicotinic acid or vitamin B3) is well established for the treatment of dyslipidemia [1] and reduction of cardiovascular risk [2].

5. examine.com examine.com/supplements/vitamin-b3/research/?srsltid=AfmBOopLFnCqiZpxKmCpY3iVJn9Qsj6LSHCFHKY0QrgaN1qb8AuoMOvS

Research Breakdown on Niacin (Vitamin B3) Supplementation results in improved cholesterol and triglyceride levels. However, since a side-effect of supplementation is increased insulin ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC280687/

The safety of over-the-counter niacin. A randomized placebo ... It is important to consult your physician before taking any nicotinic acid product. Do not use in case of pregnancy, gout, diabetes, ulcers or liver dysfunction ...

7. medchemexpress.com medchemexpress.com/niacin-hydrochloride.html?srsltid=AfmBOoo3Y5JxngqOJ4_ybWWxGsPbElCttKRK4XJKlwSJilAVaWB6QRJ1

B3 Vitamin - Niacin hydrochloride Niacin hydrochloride plays a key role in energy metabolism, cell signaling cascades regulating gene expression and apoptosis. Niacin hydrochloride is also used ...

8. lpi.oregonstate.edu lpi.oregonstate.edu/mic/vitamins/niacin

Niacin | Linus Pauling Institute | Oregon State University Niacin or vitamin B3 is a water-soluble vitamin used by the body to form the nicotinamide coenzyme, NAD+. The term 'niacin' is often used to ...