At a glance
ClinicalIndex Comparison Record- ✓RDEB patients with a nonsense mutation in COL7A1 in either one or two alleles
- ✓Absence or decrease in C7 expression at the dermal-epidermal junction compared to normal skin
- ✕Pre-existing renal or auditory impairment
- ✕Allergies to aminoglycosides or sulfate compounds
- ✕Pregnancy
- ✕Exposure to gentamicin within the past 6 weeks
Standardized by ClinicalIndex from the ClinicalTrials.gov record · verify against the source.
Gentamicin Therapy for Recessive Dystrophic Epidermolysis Bullosa Patients With Nonsense Mutations
In Brief
A Phase 2 clinical trial evaluating Gentamicin Sulfate for Recessive Dystrophic Epidermolysis Bullosa. Completed, enrolled 6 participants across 1 site.
Detailed 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.
Study Details
Timeline
Interventions
Participants will be divided into three cohorts: topical gentamicin; Topical gentamicin with microneedle roller assistance; IV gentamicin. While the intervention is the same drug, the topical gentamicin is compounded into a 0.5% ointment and the IV gentamicin is prepared to 7.5 mg/kg body weight and administered over a 30 minutes.