Gentamicin Therapy for Recessive Dystrophic Epidermolysis Bullosa (RDEB) Nonsense Mutation Patients

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. Identifier: NCT02698735
Recruitment Status : Enrolling by invitation
First Posted : March 4, 2016
Last Update Posted : April 11, 2017
Information provided by (Responsible Party):
David Woodley, University of Southern California

Brief Summary:
Recessive dystrophic epidermolysis bullosa (RDEB) is an incurable, devastating, inherited skin disease for which there is only supportive care. RDEB is due to mutations in COL7A1 gene that encodes for type VII collagen (C7), the major component of anchoring fibrils (AFs) mediating epidermal-dermal adherence. Approximately 20% of COL7A1 mutations are nonsense mutations leading to premature stop codons and a truncated C7 with diminished function. The investigators demonstrated that aminoglycosides such as gentamicin readily induce premature termination codon (PTC) "read through" and produce biologically functional C7 in 22 reported COL7A1 nonsense mutations. Importantly, aminoglycoside-induced C7 reversed the abnormal RDEB cell phenotype and incorporated into the dermal-epidermal junction. Herein, the investigators propose the first clinical trial of gentamicin (topical and intradermal) in RDEB patients with nonsense mutations that the investigators have fully characterized. The milestones include increased C7 and AFs at the patients' dermal-epidermal junction, improved RDEB Disease Activity Score, and absence of significant gentamicin side effects.

Condition or disease Intervention/treatment Phase
Recessive Dystrophic Epidermolysis Bullosa Drug: Gentamicin Drug: Placebo Not Applicable

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Study Start Date : February 2016
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : December 2017

Arm Intervention/treatment
Experimental: Gentamicin
Gentamicin antibiotic
Drug: Gentamicin
Placebo Comparator: Placebo
Vehicle control
Drug: Placebo

Primary Outcome Measures :
  1. Restoration of full-length type VII collagen as assessed by immunofluorescence. [ Time Frame: 3 months ]
  2. Restoration of anchoring fibrils as assessed by transmission electron microscopy. [ Time Frame: 3 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients with recessive dystrophic epidermolysis bullosa (RDEB) who have bona fide nonsense mutations in the COL7A1 gene

Exclusion Criteria:

  • RDEB patients who do not have a nonsense mutation in their COL7A1 gene

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: David Woodley, Professor of Dermatology, University of Southern California Identifier: NCT02698735     History of Changes
Other Study ID Numbers: HS-15-00821
First Posted: March 4, 2016    Key Record Dates
Last Update Posted: April 11, 2017
Last Verified: April 2017

Additional relevant MeSH terms:
Epidermolysis Bullosa
Epidermolysis Bullosa Dystrophica
Skin Abnormalities
Congenital Abnormalities
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases
Skin Diseases, Vesiculobullous
Collagen Diseases
Connective Tissue Diseases
Anti-Bacterial Agents
Anti-Infective Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action