A Pilot Study to Examine the Efficacy and Tolerability of Sirolimus on Epidermal Nevi Lesions in Patients 6 Years Old and Above.
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Improvement of nevi flattening and normalization of skin color
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Patients 6 years of age or older with a non-inflammatory epidermal nevi
干预措施: sirolimus topical gel 0.2% (Drug)
结局指标
主要结局
Improvement of nevi flattening and normalization of skin color
时间窗: 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
次要结局
- Satisfaction scores of treatment(12 weeks)
- Patient-reported improvement of lesion(12 weeks)
- Reduction in peak itch score(12 weeks)
研究者
Amy Paller
Professor
Northwestern University