Efficacy of Topical Gentamycin for Hereditary Hypotrichosis Simplex Caused by Nonsense Mutations in CDSN
Primary Purpose
Hereditary Hypotrichosis Simplex
Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Gentamicin Sulfate
Sponsored by
About this trial
This is an interventional treatment trial for Hereditary Hypotrichosis Simplex
Eligibility Criteria
Inclusion Criteria:
- Patients with hypotrichosis simplex of the scalp carrying a nonsense heterozygous mutation in the CDSN gene
- Patients 18 years of age or older
- Patient with normal hearing assessment within 30 days prior to treatment with the investigational drug
- Patients with normal liver and renal function
Exclusion Criteria:
- Patients with Hypotrichosis simplex of the scalp with no identified mutation in CDSN
- Patients under 18 years of age
- Patients with known hearing loss and renal and liver insufficiency
- Patients with impaired skin barrier over the scalp such as bruise, ulcer, erosion etc.
- Pregnancy and breastfeeding
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
No Intervention
Arm Label
Gentamicin Sulfate
No treatment
Arm Description
All subjects will be treated with topical gentamycin applied twice daily (1 fingertip unit (FTU)) to the right half of the scalp. Total study period: 6 months.
The medication won't be applied to the left half of the scalp.
Outcomes
Primary Outcome Measures
Hair density over the scalp
The Severity of Alopecia Tool (SALT) Score will be the measure of hair density as following: Percentage of terminal hair loss is determined at the top of the scalp (A), the back of the scalp (B), left side of the scalp (C) and right side of the scalp (D). The sum of A+B+C+D = SALT score.
Secondary Outcome Measures
The presence of vellus hairs
The appearance of vellus hair on the treated half scalp versus the untreated half scalp is a qualitative measure for Gentamycin efficacy
Activity of hair loss
The hair pull test will indicate if active hair loss is present or not, in the treated half of the scalp versus the untreated half of the scalp as a measure for Gentamycin efficacy
Photographic documentation
Pictures of the scalp will be taken to illustrate Gentamycin effect
Side effects
Patients will be asked if they experienced side effects of topical Gentamycin treatment: local site reactions such as erythema, , irritation, dryness
Full Information
NCT ID
NCT03492866
First Posted
March 18, 2018
Last Updated
April 8, 2018
Sponsor
Tel-Aviv Sourasky Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT03492866
Brief Title
Efficacy of Topical Gentamycin for Hereditary Hypotrichosis Simplex Caused by Nonsense Mutations in CDSN
Official Title
The Efficacy of Topical Gentamycin for the Treatment of Hereditary Hypotrichosis Simplex Caused by Heterozygous Nonsense Mutations in CDSN Encoding Corneodesmosin
Study Type
Interventional
2. Study Status
Record Verification Date
March 2018
Overall Recruitment Status
Unknown status
Study Start Date
April 2018 (Anticipated)
Primary Completion Date
February 2019 (Anticipated)
Study Completion Date
April 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tel-Aviv Sourasky Medical Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The scalp-limited for of hereditary hypotrichosis simplex (HHS; MIM146520) is an autosomal dominant form of non-syndromic alopecia which is caused by heterozygous nonsense mutations in the CDSN gene, encoding corneodesmosin (1). The disease features diffuse gradual scalp hair loss that starts in the middle of the first decade of life and progresses to total alopecia till the third decade of life. Recent studies have shown that aminoglycosides have the potential to induce readthrough of nonsense mutations in human cells.
The aim of this study is to investigate whether topical aminoglycosides (Gentamycin) may be beneficial for the treatment of HHS patients carrying nonsense mutations by inducing readthrough.
The Study goals:
To assess the short and long term efficacy of topical gentamycin for the treatment of hereditary hypotrichosis simplex caused by nonsense heterozygous mutations in CDSN.
The primary end point:
To assess scalp hair growth during study period as compared to baseline. Hair growth will be evaluated during enrollment and every 4 weeks. The secondary end points will be time to regrowth for determining efficacy.
Detailed Description
Study design: An open label one arm prospective study designed to evaluate the short and long term efficacy of topical gentamycin for the treatment of 8 patients with hypotrichosis simplex of the scalp.
Patients with hypotrichosis simplex of the scalp carrying a nonsense heterozygous mutation in the CDSN gene, who are eligible to the study based on inclusion/exclusion criteria, will sign the informed consent and will start to apply on the right half of scalp topical Gentamycin twice daily. The medication will not be applied to the left half of the scalp. Other local treatments to the scalp should be avoided during the study period. Daily oral medications are allowed. The patients will undergo general blood examination tests at baseline and every 4 weeks for safety measures. Blood tests include CBC, renal and liver function tests. Gentamycin levels will be assessed every 4 weeks.
Assessments on Visit 1:
Inclusion and exclusion criteria (including verifying normal hearing test at baseline prior to enrollment) Enrollment Baseline lab tests (CBC, renal and liver function tests) Physical exam SALT score Vellus hairs presence Pull test Patients self-assessment scale Photographs
Assessments on Follow up visits (every 4 weeks for a total of 6 months):
Physical exam Local site reactions SALT score Half head assessment Vellus hair presence Pull test Patients self-assessment scale Blood tests (CBC, renal and liver function tests) and gentamycin levels Photographs
Study withdrawal:
Patients with serious side effects of Gentamycin topical treatment such as hearing loss and impaired renal function or other serious side effect that according to the investigator judgment might jeopardize the patient's health. These are unexpected via local application and in the presence of intact skin.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hereditary Hypotrichosis Simplex
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Model Description
Assessing in 8 patients the efficacy of topical gentamycin treatment on 1 side of the scalp by determining the amount of hair loss on the treated versus the untreated side of the scalp
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
8 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Gentamicin Sulfate
Arm Type
Active Comparator
Arm Description
All subjects will be treated with topical gentamycin applied twice daily (1 fingertip unit (FTU)) to the right half of the scalp. Total study period: 6 months.
Arm Title
No treatment
Arm Type
No Intervention
Arm Description
The medication won't be applied to the left half of the scalp.
Intervention Type
Drug
Intervention Name(s)
Gentamicin Sulfate
Intervention Description
Topical treatment of 1 side of the scalp twice daily during 6 months
Primary Outcome Measure Information:
Title
Hair density over the scalp
Description
The Severity of Alopecia Tool (SALT) Score will be the measure of hair density as following: Percentage of terminal hair loss is determined at the top of the scalp (A), the back of the scalp (B), left side of the scalp (C) and right side of the scalp (D). The sum of A+B+C+D = SALT score.
Time Frame
During 6 months of treatment
Secondary Outcome Measure Information:
Title
The presence of vellus hairs
Description
The appearance of vellus hair on the treated half scalp versus the untreated half scalp is a qualitative measure for Gentamycin efficacy
Time Frame
During 6 months of treatment
Title
Activity of hair loss
Description
The hair pull test will indicate if active hair loss is present or not, in the treated half of the scalp versus the untreated half of the scalp as a measure for Gentamycin efficacy
Time Frame
During 6 months of treatment
Title
Photographic documentation
Description
Pictures of the scalp will be taken to illustrate Gentamycin effect
Time Frame
During 6 months of treatment
Title
Side effects
Description
Patients will be asked if they experienced side effects of topical Gentamycin treatment: local site reactions such as erythema, , irritation, dryness
Time Frame
During 6 months of treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with hypotrichosis simplex of the scalp carrying a nonsense heterozygous mutation in the CDSN gene
Patients 18 years of age or older
Patient with normal hearing assessment within 30 days prior to treatment with the investigational drug
Patients with normal liver and renal function
Exclusion Criteria:
Patients with Hypotrichosis simplex of the scalp with no identified mutation in CDSN
Patients under 18 years of age
Patients with known hearing loss and renal and liver insufficiency
Patients with impaired skin barrier over the scalp such as bruise, ulcer, erosion etc.
Pregnancy and breastfeeding
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Udi Ben Dor
Phone
054-3177030
Email
udibd@tlvmc.gov.il
First Name & Middle Initial & Last Name or Official Title & Degree
Orna Dagan
Phone
054-4708065
Email
ornad@tlvmc.gov.il
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Liat Samuelov
Organizational Affiliation
Deprt. of Dermatology, Tel Aviv Sourasky MC
Official's Role
Study Director
12. IPD Sharing Statement
Learn more about this trial
Efficacy of Topical Gentamycin for Hereditary Hypotrichosis Simplex Caused by Nonsense Mutations in CDSN
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