Patients at Risk for Melanoma
Conditions
Brief summary
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.
Interventions
DRUGN-acetylcysteine
N-acetylcysteine (NAC), 1200 mg Oral route 2 doses
OTHERPlacebo arm
Sterile normal saline, diluted into 25 cc tomato juice, orally, x 1 dose. Then repeated 24 hours later.
Sponsors
University of Utah
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| UV-induced Oxidative Stress in Irradiated and Unirradiated Nevi | 3.5 years | Differences in the median percent nevus with 8-OG expression in UV-irradiated nevi compares with unirradiated nevi. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Transcriptional Markers of UV-induced Oxidative Stress in Nevi | 3.5 years | Biomarkers susceptible to UV-induced damage protected by NAC (N-acetylcysteine) in irradiated and unirradiated nevi |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Patients Receiving N-acetylcysteine Patients receiving NAC (N-acetylcysteine)
N-acetylcysteine: N-acetylcysteine (NAC), 1200 mg Oral route 2 doses | 50 |
| Placebo Group Participants not receiving NAC (N-acetylcysteine)
Placebo arm: Sterile normal saline, diluted into 25 cc tomato juice, orally, x 1 dose.
Then repeated 24 hours later. | 50 |
| Total | 100 |
Baseline characteristics
| Characteristic | Patients Receiving N-acetylcysteine | Placebo Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 4 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 47 Participants | 46 Participants | 93 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 50 Participants | 50 Participants | 100 Participants |
| Region of Enrollment United States | 50 Participants | 50 Participants | 100 Participants |
| Sex: Female, Male Female | 22 Participants | 17 Participants | 39 Participants |
| Sex: Female, Male Male | 28 Participants | 33 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 50 |
| other Total, other adverse events | 0 / 50 | 0 / 50 |
| serious Total, serious adverse events | 0 / 50 | 0 / 50 |
Outcome results
Primary
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.
Time frame: 3.5 years
Population: One subject with low-risk MC1R randomized to drug was excluded from both analyses because the lesions removed were seborrheic keratoses and not nevi, and 2 subjects (one high-risk MC1R randomized to drug and one low-risk MC1R randomized to placebo) were excluded from analysis of 8-OG because there was insufficient tissue.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Patients Receiving N-acetylcysteine | UV-induced Oxidative Stress in Irradiated and Unirradiated Nevi | UV Irradiated | 94.6 percentage of 8-OG expression in nevi | Standard Deviation 12.3 |
| Patients Receiving N-acetylcysteine | UV-induced Oxidative Stress in Irradiated and Unirradiated Nevi | Unirradiated | 33.6 percentage of 8-OG expression in nevi | Standard Deviation 25.1 |
| Placebo Group | UV-induced Oxidative Stress in Irradiated and Unirradiated Nevi | UV Irradiated | 96.2 percentage of 8-OG expression in nevi | Standard Deviation 7.5 |
| Placebo Group | UV-induced Oxidative Stress in Irradiated and Unirradiated Nevi | Unirradiated | 33.1 percentage of 8-OG expression in nevi | Standard Deviation 24.2 |
p-value: 0.65Wilcoxon (Mann-Whitney)
Secondary
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
Time frame: 3.5 years
Population: One subject with low-risk MC1R randomized to drug was excluded because the lesions removed were seborrheic keratoses and not nevi.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Patients Receiving N-acetylcysteine | Transcriptional Markers of UV-induced Oxidative Stress in Nevi | GCLM Biomarker | 8.99 markers of UV-induced oxidative stress | Standard Deviation 0.83 |
| Patients Receiving N-acetylcysteine | Transcriptional Markers of UV-induced Oxidative Stress in Nevi | SLC1A4 Biomarker | 9.29 markers of UV-induced oxidative stress | Standard Deviation 0.87 |
| Patients Receiving N-acetylcysteine | Transcriptional Markers of UV-induced Oxidative Stress in Nevi | SLC7A11 Biomarker | 8.73 markers of UV-induced oxidative stress | Standard Deviation 1.13 |
| Placebo Group | Transcriptional Markers of UV-induced Oxidative Stress in Nevi | GCLM Biomarker | 9.14 markers of UV-induced oxidative stress | Standard Deviation 0.75 |
| Placebo Group | Transcriptional Markers of UV-induced Oxidative Stress in Nevi | SLC1A4 Biomarker | 9.40 markers of UV-induced oxidative stress | Standard Deviation 1.06 |
| Placebo Group | Transcriptional Markers of UV-induced Oxidative Stress in Nevi | SLC7A11 Biomarker | 9.03 markers of UV-induced oxidative stress | Standard Deviation 0.95 |
Comparison: GCLM Biomarker analysis.p-value: 0.76ANCOVA
Comparison: SLC1A4 Biomarker analysis.p-value: 0.63ANCOVA
Comparison: SLC7A11 Biomarker analysis.p-value: 0.27ANCOVA