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Intravenous Gentamicin Therapy for Recessive Dystrophic Epidermolysis Bullosa (RDEB)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03392909
Recruitment Status : Recruiting
First Posted : January 8, 2018
Last Update Posted : November 4, 2020
Information provided by (Responsible Party):
David Woodley, University of Southern California

Tracking Information
First Submitted Date  ICMJE January 2, 2018
First Posted Date  ICMJE January 8, 2018
Last Update Posted Date November 4, 2020
Actual Study Start Date  ICMJE July 5, 2018
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 2, 2018)
  • Full-length type VII collagen expression [ Time Frame: 6 months ]
    Increased expression of full-length type VII collagen as assessed by immunofluorescence
  • Generation of anchoring fibrils [ Time Frame: 6 months ]
    Generation of new anchoring fibrils as assessed by immuno-electron microscopy
  • Absence of gentamicin side effects [ Time Frame: 6 months ]
    Absence of gentamicin side effects, especially the detection of any ototoxicity or nephrotoxicity
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 2, 2018)
  • Improved Disease Activity scores [ Time Frame: 6 months ]
    Improved epidermolysis bullosa Disease Activity scores
  • Improved Quality of Life score [ Time Frame: 6 months ]
    Improved Quality of Life score
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Intravenous Gentamicin Therapy for Recessive Dystrophic Epidermolysis Bullosa (RDEB)
Official Title  ICMJE Restoration of Full-Length Type VII Collagen in RDEB Patients With Nonsense Mutations After Intravenous Gentamicin Treatment
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 milestones will be increased C7 and AFs in the patients' DEJ, improved EB Disease Activity Scores, and absence of gentamicin side effects.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Recessive Dystrophic Epidermolysis Bullosa
Intervention  ICMJE Drug: Gentamicin
Short-term intravenous gentamicin therapy should have the advantage of treating all of the patient's multiple skin wounds simultaneously. Six patients (three adults and 3 children) will receive intravenous gentamicin (7.5 mgs/kg) daily for 14 days and then stopped. Three adult patients will receive intravenous gentamicin (7.5mg/kg) biweekly for three months and then stopped.
Other Name: Gentamicin Sulfate
Study Arms  ICMJE Experimental: Intravenous Gentamicin
Intravenous gentamicin (7.5 mgs/kg) daily for for either 14 days and then stopped or twice weekly for three months and then stopped.
Intervention: Drug: Gentamicin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 2, 2018)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2021
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Provision of signed and dated informed consent form
  • Stated willingness to comply with all study procedures and availability for the duration of the study
  • Male or female, aged 7 and up can participate in the 14 day IV gentamicin trial. Male or female, aged 18 and up can participate in the 3 month IV gentamicin trial.
  • Been diagnosed with recessive dystrophic epidermolysis bullosa (RDEB) and with a nonsense mutation in the COL7A1 gene.
  • Immunofluorescence evaluation of skin biopsies reveals absence or decreased intensity of C7 expression at their DEJ (dermal epidermal junction) compared with normal human skin biopsies.
  • Cultured fibroblasts from patient skin synthesize and secrete full-length, 290kDa C7 alpha chains in the presence of supplemented gentamicin (400 μg/ml in culture).
  • Ability to sit or lie down for over 30 minutes for IV infusions. For those in the 3 month trial, to be willing to continue treatment at home under the supervision of licensed and trained infusion nurses.

Exclusion Criteria:

  • Recent exposure to gentamicin within the past 6 weeks.
  • Pre-existing known auditory impairment.
  • Pre-existing known renal impairment.
  • Pre-existing known allergies to aminoglycosides or sulfate compounds.
  • Pregnancy or lactation
  • Current use of medications with known ototoxicity or nephrotoxicity.
  • Current enrollment in another experimental clinical trial involving systemic treatment with C7 or C7 producing products for the treatment of RDEB.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 7 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: David T Woodley, MD 626-533-6028
Contact: Mei Chen, Ph.D 323-865-0621
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT03392909
Other Study ID Numbers  ICMJE HS-17-00995
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party David Woodley, University of Southern California
Study Sponsor  ICMJE University of Southern California
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: David T. Woodley, MD Professor, University of Southern California
Principal Investigator: Mei Chen, Ph.D Professor, University of Southern California
PRS Account University of Southern California
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP