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Using Topical Sirolimus 2% for Patients With Epidermolysis Bullous Simplex (EBS) Study

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02960997
First Posted: November 10, 2016
Last Update Posted: November 14, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Joyce Teng, Stanford University
  Purpose
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.

Condition Intervention Phase
Epidermolysis Bullosa Simplex Epidermolysis Bullosa Simplex Kobner Weber-Cockayne Syndrome Drug: Sirolimus, 2% Drug: Vehicle Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Joyce Teng, Stanford University:

Primary Outcome Measures:
  • Foot Health Status Questionnaire [ Time Frame: Change from Baseline to End of Treatment completion at 32 Week ]
    Foot function utilizing the validated Foot Health Status Questionnaire (FHSQ) as a change from baseline to the end of each treatment.


Secondary Outcome Measures:
  • FitBit® / pedometer [ Time Frame: Baseline and through study treatment completion at 32-weeks ]
  • plantar defect size using 3D Photography [ Time Frame: Change in total defect area from Baseline, clinical visits at Week 4, Week 12, Week 16, Week 28, through study treatment completion at 32-weeks ]
    Plantar defect size measurements using 3D photography (% change in total defect area) from baseline to the end of each treatment.

  • Child Dermatological Quality of Life Questionnaire [ Time Frame: Baseline and through study treatment completion at 32-weeks ]
  • The Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) Disease Severity Scale [ Time Frame: Baseline and through study treatment completion at 32-weeks ]

Estimated Enrollment: 8
Study Start Date: May 2016
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: May 31, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
Sirolimus, 2% topical ointment will be used during randomization
Drug: Sirolimus, 2%
Placebo Comparator: Vehicle
A placebo topical ointment will be used during randomization.
Drug: Vehicle
Other Name: Placebo

Detailed Description:

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.

  Eligibility

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Ages Eligible for Study:   5 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 5-18 yo.
  • Be male or female with a diagnosis of EBS
  • Minimum EBDASI feet activity score of 2/10
  • Age - 5 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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02960997


Locations
United States, California
Stanford University
Palo Alto, California, United States, 94304
Sponsors and Collaborators
Stanford University
Investigators
Study Chair: Joyce M Teng, MD, PhD Stanford School of Medicine
  More Information

Publications:

Responsible Party: Joyce Teng, Director of Pediatric Dermatology, Stanford University
ClinicalTrials.gov Identifier: NCT02960997     History of Changes
Other Study ID Numbers: 35498
First Submitted: June 15, 2016
First Posted: November 10, 2016
Last Update Posted: November 14, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Keywords provided by Joyce Teng, Stanford University:
epidermolysis bullosa simplex

Additional relevant MeSH terms:
Epidermolysis Bullosa
Epidermolysis Bullosa Simplex
Cockayne Syndrome
Skin Abnormalities
Congenital Abnormalities
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases
Skin Diseases, Vesiculobullous
Dwarfism
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Nervous System Diseases
Abnormalities, Multiple
DNA Repair-Deficiency Disorders
Metabolic Diseases
Sirolimus
Everolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs