Metabolomic and Inflammatory Effects of Oral Aspirin (ASA) in Subjects at Risk for Melanoma

Study Overview
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Brief Summary
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This is an open label phase II pilot study assessing the metabolomic and inflammatory effects of oral aspirin (ASA) in human subjects at risk for melanoma.

Detailed Description
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Primary Objectives I. Open label trial in 60 patients to assess the capacity of either of one daily dose (81, 325 mg) of sub-chronic ASA administration to increase the plasma and nevus ASA metabolites such as: salicylate, salicylurate, gentisic acid, and salicyl acyl glucuronide. II. Open label trial in 60 patients to assess the capacity of sub-chronic daily ASA (81, 325 mg) administration to reduce levels of prostaglandin E2 (PGE2) in plasma and nevi. Secondary Objectives I. Determine whether ASA increases AMP-activated protein kinase (AMPK) activation in nevi. II. Determine whether ASA affects whole blood leukocytes or leukocyte subsets in plasma. III. Determine whether ASA affects inflammatory cytokines in plasma.

Official Title
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Pilot Studies Assessing the Metabolomic and Inflammatory Effects of Oral Aspirin (ASA) in Human Subjects at Risk for Melanoma

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Drug: Aspirin 81 mg
* Drug: Aspirin 325mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have at least 2 nevi (each >5 mm diameter) not clinically suspicious for melanoma that can be biopsied. Must be older than age 18. Must be able to receive informed consent and sign an approved consent form that conforms to federal and institutional guidelines. Exclusion Criteria: The patient is a minor, under age 18. The patient cannot speak / understand English or Spanish. The patient is pregnant or breastfeeding. The patient is a prisoner, critically or mentally ill, or otherwise incapacitated or considered vulnerable. The patient has history of allergic reaction to ASA. The patient has history of severe asthma. The patient has been taking ASA or any NSAID in the past 2 weeks. The patient has been taking a blood thinner in the past 2 weeks. The patient has history of bleeding disorder. The patient has history of peptic ulcer disease. The patient has had recent intense UV exposure in the past month.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ASA 81 mg daily<br>Participants will be given ASA 81 mg orally once daily for a total of 7 days | Drug: Aspirin 81 mg<br>* ASA 81mg taken daily<br>* Other names: ASA;|
| Experimental: ASA 325 mg daily<br>Participants will be given ASA 325 mg orally once daily for a total of 7 days. | Drug: Aspirin 325mg<br>* ASA 325mg taken daily<br>* Other names: ASA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in concentration of ASA metabolites (salicylate and salicylurate) in plasma after ASA ingestion | Concentration (ng/mL) of pre-treatment ASA metabolites (salicylate and salicylurate) in plasma will be compared to the concentration of ASA metabolites at day 7 | Change from baseline to day 7 | 
| Change in concentration of ASA metabolites in nevus tissue after ASA ingestion | Pre-treatment ASA metabolites in tissue will be compared to ASA metabolites at day 7 | Change from baseline to day 7 | 
| Change in concentration of prostaglandin E2 (PGE2) in plasma after ASA ingestion | Baseline PGE2 levels in plasma specimens will be compared to PGE2 levels at day 7. | Change from baseline to day 7 | 
| Change in concentration of prostaglandin E2 (PGE2) in nevus tissue after ASA ingestion | Baseline PGE2 levels in tissue specimens will be compared to PGE2 levels at day 7. | Change from baseline to day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in AMP-activated protein kinase (AMPK) activation in nevi after ASA ingestion | Quantitative densitometry analysis using Western blots will be performed on tissue collected at baseline and at day 7 to compare activation of AMP-activated protein kinase (AMPK). | Change from baseline to day 7 | 
| Change in concentration of leukocytes in peripheral blood after ASA ingestion | Whole blood will be taken at baseline and at day 7 to compare concentration of leukocytes | Change from baseline to day 7 |