Oral N-acetylcysteine for Protection of Human Nevi Against UV-induced Oxidative Stress/Damage in Vivo

Study Overview
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Brief Summary
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This is a phase II intervention to propose a new melanoma chemoprevention agent. The investigators believe oxidative stress/damage in nevi is a probable indication for melanoma risk, and propose that reduced melanoma risk in humans can be inferred by protection of nevi from ultraviolet light (UV)-induced oxidative changes. The investigators will 1) evaluate whether administration of NAC around the time of UV exposure will reduce melanoma risk in high-risk patient populations with genetic susceptibility to UV-induced oxidative stress, and 2) examine key genetic variants that will identify which individuals are most likely to benefit from chemoprotection.

Official Title
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A Phase II Placebo-controlled Intervention Trial of Oral N-acetylcysteine (NAC) for Protection of Human Nevi Against UV-induced Oxidative Stress/Damage in Vivo

Conditions
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Patients at Risk for Melanoma

Intervention / Treatment
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* Drug: N-acetylcysteine
* Other: Placebo arm


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have at least 2 nevi (each >6 mm diameter) not clinically suspicious for melanoma that can be biopsied. 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 (< 18 years old). The patient cannot speak/understand English or Spanish. (NOTE: A Spanish consent form and certified interpreter can be made available if needed) The patient is pregnant. (NOTE: All female patients who have not had a hysterectomy and are not post-menopausal (i.e. post-menopausal for 1 year and not of child-bearing potential) will have a urine pregnancy test.) The patient is a prisoner, critically or mentally ill, or otherwise incapacitated or considered vulnerable. The patient has history of allergic reaction to NAC. The patient has history of severe asthma. The patient has been taking NAC or any other oral antioxidant. The patient has recent history (i.e., 3 months) of sunless tanning (tanning bed) or extensive sunburn.

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: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients receiving N-acetylcysteine<br>Patients receiving NAC (N-acetylcysteine) | Drug: N-acetylcysteine<br>* N-acetylcysteine (NAC), 1200 mg Oral route 2 doses<br>* Other names: NAC;|
| Placebo Comparator: Placebo Group<br>Participants not receiving NAC (N-acetylcysteine) | Other: Placebo arm<br>* Sterile normal saline, diluted into 25 cc tomato juice, orally, x 1 dose. Then repeated 24 hours later.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| UV-induced Oxidative Stress in Irradiated and Unirradiated Nevi | Differences in the median percent nevus with 8-OG expression in UV-irradiated nevi compares with unirradiated nevi. | 3.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transcriptional Markers of UV-induced Oxidative Stress in Nevi | Biomarkers susceptible to UV-induced damage protected by NAC (N-acetylcysteine) in irradiated and unirradiated nevi | 3.5 years |