Using Topical Sirolimus 2% for Patients With Epidermolysis Bullous Simplex (EBS) Study
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Skin and Soft Tissue Infections, Dermatology |
| Therapuetic Areas: | Dermatology / Plastic Surgery |
| Healthy: | No |
| Age Range: | 4 - Any |
| Updated: | 9/8/2018 |
| Start Date: | May 2016 |
| End Date: | December 13, 2020 |
A Prospective, Double-Blind, Cross-Over, Pilot Study to Assess Safety and Efficacy of Topical Sirolimus 2% in the Treatment of Plantar Blistering in Patients With Epidermolysis Bullous Simplex (EBS)
Epidermolysis bullosa (EB) simplex is a rare orphan disease caused by a mutation in DNA
leading to abnormal dominant keratins in the skin. Patients with EB simplex develop lifelong
painful thick soles on their feet, and current standard of care is supportive. This pilot
study will target the dominant mutant keratin proteins in the skin to ameliorate the severity
of EB simplex. The purpose is to improve the function of EB simplex feet with an application
of topical sirolimus, 2%. The investigators plan on inhibiting the mTOR pathway to down
regulate the translation of defective keratin proteins and work through anti proliferative
pathways.
leading to abnormal dominant keratins in the skin. Patients with EB simplex develop lifelong
painful thick soles on their feet, and current standard of care is supportive. This pilot
study will target the dominant mutant keratin proteins in the skin to ameliorate the severity
of EB simplex. The purpose is to improve the function of EB simplex feet with an application
of topical sirolimus, 2%. The investigators plan on inhibiting the mTOR pathway to down
regulate the translation of defective keratin proteins and work through anti proliferative
pathways.
The proposed 40 week pilot study being conducted is a prospective, double-blind, randomized,
placebo-controlled crossover study. Participants will be assigned to treat both feet with
either topical sirolimus, 2% cream daily or placebo (vehicle-control) for 12 weeks, followed
by a 4 week washout period, then re-treatment to both feet will occur by the cross-over
intervention.
These studies will exploit the naturally occurring transcriptional regulation of keratin
sequences, the known gene aberration causing EB simplex, and assess the potential for mTOR
pathway inhibition in treatment of the patient's plantar lesions. The objective of this study
is to assess (1) the safety of topical rapamycin for plantar lesions for the treatment of EB
simplex, and 2) test if topical rapamycin to improves the clinical severity of lesional skin,
including pain and itch, in subjects with EB simplex at the end of treatment versus baseline
and compared to an intrasubject placebo treated control. Wound size measurement, quality of
life evaluation will be assessed using epidermolysis bullosa (QOLEB), and EB disease activity
and Scarring Index (EBDASI). With the results of this pilot study, physicians would be able
to transition from supportive care (the current state of the art for EB simplex) to targeted
molecular therapeutics, leading to improved mobility and quality of life for patients with EB
simplex.
placebo-controlled crossover study. Participants will be assigned to treat both feet with
either topical sirolimus, 2% cream daily or placebo (vehicle-control) for 12 weeks, followed
by a 4 week washout period, then re-treatment to both feet will occur by the cross-over
intervention.
These studies will exploit the naturally occurring transcriptional regulation of keratin
sequences, the known gene aberration causing EB simplex, and assess the potential for mTOR
pathway inhibition in treatment of the patient's plantar lesions. The objective of this study
is to assess (1) the safety of topical rapamycin for plantar lesions for the treatment of EB
simplex, and 2) test if topical rapamycin to improves the clinical severity of lesional skin,
including pain and itch, in subjects with EB simplex at the end of treatment versus baseline
and compared to an intrasubject placebo treated control. Wound size measurement, quality of
life evaluation will be assessed using epidermolysis bullosa (QOLEB), and EB disease activity
and Scarring Index (EBDASI). With the results of this pilot study, physicians would be able
to transition from supportive care (the current state of the art for EB simplex) to targeted
molecular therapeutics, leading to improved mobility and quality of life for patients with EB
simplex.
Inclusion Criteria:
Subjects must:
- Be capable of understanding the purpose and risks of the study and sign a written
Informed Consent Form (ICF); Legally authorized representative of subjects willing and
able to give consent for children 4-18 yo.
- Be male or female with a diagnosis of EBS
- Minimum EBDASI feet activity score of 2/10
- Age - 4 years or older
- Ability to complete 12 study visits within a 40-week period, each for approximately
30-60 minutes.
- Anticipated life expectancy ≥52 weeks.
- Males and females of childbearing potential should be using an effective means of
contraception.
- Laboratory values within the range of normal for the participating institution unless
the PI feels they are not clinically relevant
- Be able to comply with all study requirements
Exclusion Criteria:
- Allergy to sirolimus or components of the vehicle ointment
- Pregnancy, breast feeding
- Prior history of liver disease
- Serious known concurrent medical illness or infection, which could potentially present
a safety risk and/or prevent compliance with the requirements of the treatment
program.
- Known immunodeficiency virus or syndrome including those with:
- Acquired Immunodeficiency Syndrome (AIDS)
- Human Immunodeficiency Virus (HIV)
- Hepatitis B
- Prior history of grafting surgeries or other surgeries in the dermatologic treatment
area
- History of significant condition in the dermatologic treatment area such as trauma,
which could impair evaluation for the treatment of EBS or non-healing chronic wound.
- Use of other investigational drugs within 30 days of the screening visit and/or has
not recovered from any side effects of prior investigational drugs or procedure in the
affected area (e.g., a biopsy).
- Use of acitretin within the last 1 month
- Use of Roaccutane within last 3 months
- Botox injections to the feet within the last 6 months.
- Participant is planning extra physical activities within the next 3 months.
- Amputated foot
We found this trial at
1
site
Click here to add this to my saved trials
