Recruiting
Phase 1
Phase 2

Gentamicin

Sponsor:

University of Southern California

Code:

NCT03392909

Conditions

Recessive Dystrophic Epidermolysis Bullosa

Eligibility Criteria

Sex: All

Age: 7+

Healthy Volunteers: Not accepted

Interventions

Gentamicin

Study Details

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.

Conditions

Recessive Dystrophic Epidermolysis Bullosa

Study ID

NCT03392909

Start date

Jul 5, 2018

Status verified date

Nov, 2022

Completion date

Dec 1, 2023

Anticipated

Primary completion date

Dec 1, 2023

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 7+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

9 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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.

Interventions

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.

Primary outcome measure

  • Full-length type VII collagen expression [ Time Frame: 6 months ]
  • Generation of anchoring fibrils [ Time Frame: 6 months ]
  • Absence of gentamicin side effects [ Time Frame: 6 months ]

Central Contacts and Locations

Central contacts

David T Woodley, MD

626-533-6028dwoodley@usc.edu

Mei Chen, Ph.D

323-865-0621chenm@usc.edu

Locations

University of Southern California

Recruiting

Los Angeles, California, United States, 90033

Contacts

David Woodley, MD

323-865-0956dwoodley@usc.edu

Mei Chen, Ph.D

323-865-0621chenm@usc.edu

More Information

Sponsor

University of Southern California

Last update posted

Nov 3, 2022

Last verified

Nov, 2022

Keywords

  • Nonsense Mutations

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by University of Southern California on 2022-11-03.