Gentamicin Therapy for Recessive Dystrophic Epidermolysis Bullosa Patients With Nonsense Mutations

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: NCT03012191
Recruitment Status : Unknown
Verified January 2017 by David Woodley, University of Southern California.
Recruitment status was:  Recruiting
First Posted : January 6, 2017
Last Update Posted : January 6, 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 caused by mutations in the COL7A1 gene that encodes for type VII collagen (C7), the major component of anchoring fibrils (AFs), structures that mediate epidermal-dermal adherence. Thirty percent of RDEB patients have nonsense mutations. The investigators recently demonstrated in 5 such patients that intradermal and topical gentamicin induced "read-through" of their nonsense mutations and created robust and sustained new C7 and AFs at the dermal-epidermal junction (DEJ) of their skin and also stimulated wound closure and reduced new blister formation. No untoward side effects occurred. Herein, the investigators propose evaluating the safety and efficacy of intravenous gentamicin in these patients. In theory, this intravenous administration has the possibility of treating simultaneously all of the patients' skin wounds. The investigators also propose optimizing the concentration and manner of delivery of topical gentamicin. The unambiguous milestones will be increased C7 and AFs in the patients' DEJ, improved EB Disease Activity Scores, and absence of significant gentamicin side effects.

Condition or disease Intervention/treatment Phase
Recessive Dystrophic Epidermolysis Bullosa Drug: Gentamicin Sulfate Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 7 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Study Start Date : January 2017
Estimated Primary Completion Date : January 2018

Arm Intervention/treatment
Experimental: Gentamicin Drug: Gentamicin Sulfate

Primary Outcome Measures :
  1. Increased expression of full-length type VII collagen as assessed by immunofluorescence [ Time Frame: 6 months ]
  2. Generation of new anchoring fibrils as assessed by immuno-electron microscopy [ Time Frame: 6 months ]
  3. Absence of gentamicin side effects especially the detection of any ototoxicity or nephrotoxicity [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. Improved epidermolysis bullosa Disease Activity Scores [ Time Frame: 6 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 as assessed by genotyping-

Exclusion Criteria:

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

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 identifier (NCT number): NCT03012191

Contact: David Woodley, MD 3238650956
Contact: Mei Chen, Ph.D 3238650621

United States, California
University of Southern California Recruiting
Los Angeles, California, United States, 90033
Contact: David Woodley, MD    323-865-0956   
Contact: Mei Chen, Ph.D    3238650621   
Sponsors and Collaborators
University of Southern California

Responsible Party: David Woodley, Professor, University of Southern California Identifier: NCT03012191     History of Changes
Other Study ID Numbers: HS-16-00788
First Posted: January 6, 2017    Key Record Dates
Last Update Posted: January 6, 2017
Last Verified: January 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