Epidermal Nevi
Conditions
Keywords
epidermal nevi, topical sirolimus, Hyftor, mTOR
Brief summary
We hypothesize that topical sirolimus could suppress the mTOR activation of linear verrucous epidermal nevi, particularly when the variants are involving genes upstream of mTOR and perhaps even those of the RAS pathway through crosstalk and downstream signaling. Indeed, a recent study noted a few cases of epidermal nevi that were improved within 3-4 months by the use of topical sirolimus. We propose to perform a pilot study of epidermal nevi to observe the impact of treatment twice daily of epidermal nevi with serial photography and scoring to capture alterations during the 3 months of the study. We will also grade local tolerance to the topical gel.
Detailed description
Epidermal nevi are skin growths that develop because of a genetic change that occurs after conception, meaning only some skin cells are affected. These growths appear as thickened, often darker areas of skin that form lines or swirls. On the arms and legs, they usually appear as straight streaks, while on the trunk and face they follow curved patterns called the lines of Blaschko, which reflect how skin cells develop before birth. These skin changes are caused by specific genetic changes that turn on certain cell growth pathways inside skin cells. Most linear verrucous epidermal nevi involve one of two major pathways that control cell growth: the PI3K/AKT/mTOR pathway or the RAS/MAPK pathway. In more than 40% of cases, changes in the FGFR3 or PIK3CA genes cause constant activation of the PI3K/AKT/mTOR pathway, leading to excess skin growth. Sirolimus (also called rapamycin) is a medication that blocks the mTOR pathway, slowing down cell growth and protein production. Medications like this are already used to treat certain cancers caused by overactive mTOR signaling. Topical sirolimus is FDA-approved as a 0.2% gel (Hyftor) to treat facial angiofibromas in people with tuberous sclerosis complex (TSC). In TSC, genetic changes cause the mTOR pathway to be overly active, leading to skin growths called angiofibromas. Studies have shown that applying sirolimus to the skin can reduce the size and visibility of these lesions.
Interventions
DRUGsirolimus topical gel 0.2%
Topical sirolimus will be applied twice daily to the nevi with a maximum daily dose of 600 mg for patients 6-11 years of age and 800 mg for patients 12 years and older.
Sponsors
Northwestern University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients 6 years of age or above with a non-inflammatory epidermal nevi * Lesion(s) that have been present for at least 3 years and are relatively stable * At least 2 cm in length (ideally continuous, but can be cumulatively) * The lesions is raised, hyperpigmented compared to the surrounding skin, and is noninflammatory with a physician global assessment (PGA) of at least 3 (moderate). * Agree to avoid emollient use at the nevus site throughout the study * Agree to not bath or shower 2 hours post-application, knowing that the gel can be applied after bathing or showering.
Exclusion criteria
* Patients currently or recently (within past 4 weeks) using a topical keratolytic or topical anti-inflammatory medication at the lesional site (i.e. topical steroid, topical retinoid, alpha-OH acid) * Pregnant or planning to become pregnant during the course of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Improvement of nevi flattening and normalization of skin color | 12 weeks | The extent of nevi improvement will be scored at baseline and week 12 from standardized photographs by two independent asessors with an adjudicator (if needed). The score will be defined as follows: 0 = 100% improvement 1. = 90-99% improvement 2. = 69-89% improvement 3. = 50-69% improvement 4. = 30-49% improvement 5. = 10-29% improvement 6. = 0-9% improvement 7. = worsening |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Satisfaction scores of treatment | 12 weeks | Patients (and parents/LAR) will be asked for their satisfaction of the treatment (not satisfied, satisfied, very satisfied) at week 12 |
| Patient-reported improvement of lesion | 12 weeks | Patients (and parents/LAR) will be asked their self-evaluation of lesion improvment from 0-5 (0= cleared, 1= almost cleared, 2= good improvement, 3= slight improvement, 4= no change, 5= worse) at baseline and week 12 |
| Reduction in peak itch score | 12 weeks | At least 2-point reduction in peak itch NRS score (on a scale of 0-10, 0=no itch and 10=worse itch) from baseline to week 12 |
Countries
United States
Contacts
CONTACTDermatology CTU
PRINCIPAL_INVESTIGATORAmy Paller, MD
Northwestern University
Outcome results
None listed