Active topical nail solution versus placebo for the treatment of pedal onychomycosis
| ISRCTN | ISRCTN77852934 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN77852934 |
| Secondary identifying numbers | AFMC 16 |
- Submission date
- 18/07/2024
- Registration date
- 27/07/2024
- Last edited
- 22/01/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English Summary
Background and study aims
This study focuses on onychomycosis (toenail fungus) and aims to compare therapeutic outcomes between an active topical solution that is applied to the affected toenail and a placebo (inactive) solution. Toenail fungus, also known as onychomycosis or tinea unguium, is a very common pathology that affects many people the world over, and it can be difficult to eradicate.
Who can participate?
Males and non-pregnant females 18 years of age or older who have been diagnosed with pedal onychomycosis involving at least one toenail
What does the study involve?
Participants will be randomly allocated to either the active or placebo (inactive) topical toenail solution group. At the first (baseline) study visit, the participant will answer a questionnaire that provides information about the influence that toenail fungus has on the individual, the study doctor will take a photograph of the most representative (index) toenail and make a measurement of the thickness of the nail, a specimen of the nail will be obtained for mycological assessment (a PAS stain to identify the microscopic presence or absence of fungus in the toenail), and basic information about the participants medical history and physical status will be obtained. At follow-up visits 3, 7 and 9 months later, the medical history and physical status information, questionnaire, a new photograph and measurement of the index toenail, and a specimen for the PAS stain test will be obtained. The outcomes will be compared between the active and placebo (inactive) treatment groups, with the aim of determining whether or not the active treatment group eliminated the presence of fungus in the toenail and improved the participants' outcomes.
What are the possible benefits and risks of participating?
Participants may potentially benefit by getting the active topical agent toenail solution and if a participant is randomly assigned to the placebo topical nail solution, they will be eligible to receive the active agent after completion of the study follow-up period. Potential risks of participating in the study are unlikely and include the possibility of developing skin irritation or sensitivity to the applied solution. It is also possible that toenail fungus could worsen in a participant assigned to the placebo group. However, as noted, such participants will be eligible to receive the active solution.
Where is the study run from?
The office of D. Scot Malay, DPM, MSCE, Philadelphia (USA)
When is the study starting and how long is it expected to run for?
April 2019 to October 2024
Who is funding the study?
Marlinz Pharma (USA)
Who is the main contact?
D. Scot Malay, malaydsm@gmail.com
Contact information
Public, Scientific
Penn Podiatry University City
3801 Filbert Street, Suite 111
Philadelphia
19146
United States of America
 ORCID ID |
0000-0002-2400-5629 |
|---|---|
| Phone | +1 (0)4848440755 |
| malaydsm@gmail.com |
Principal Investigator
Foot & Ankle Specialists of Nevada
3212 Wisteria Tree Street
Las Vegas, Nevada
89135
United States of America
| Phone | +1 (0)(702) 701-3186 (cell) Contact: Self |
|---|---|
| docbregman@gmail.com |
Study information
| Study design | Multicenter interventional double-blind randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | GP practice |
| Study type | Treatment |
| Scientific title | A randomized, controlled trial to determine the efficacy of active topical nail solution versus placebo nail solution for the treatment of pedal onychomycosis |
| Study acronym | RCTATNP |
| Study hypothesis | Participants undergoing topical application of the active topical nail solution for the treatment of toenail onychomycosis will display a higher incidence of nail plate improvement, both clinical and mycological, in comparison to participants undergoing application of the topical placebo agent. |
| Ethics approval(s) |
Approved 14/05/2021, WCG IRB (1019 39th Avenue, Suite 120, Puyallup, Washington, 98374, United States of America; +1 (0)855 818 2289; jkelly@cgirb.com), ref: 20211891 |
| Condition | Onychomycosis (tinea unguium) localized to toenails |
| Intervention | The main clinical disease under evaluation is toe onychomycosis. Participants will be males and non-pregnant females 18 years of age or older who have been diagnosed with distal subungual onychomycosis (DSO) involving at least one toenail. Diagnosis of this condition is to be made on the basis of history, physical examination, and a mycological inspection that includes a tissue examination for fungal hyphae (PAS stain). Evidence of fungal hyphae will be considered a positive confirmation of the diagnosis of toenail onychomycosis. All participants will be randomized to either the active topical nail solution group, antifungal solution treatment, or to the placebo nail solution group. Randomization will be carried out by means of electronic random number generation under the authority of a co-investigator (HRK), who will prepare sealed, sequentially numbered envelopes for each study site (A to J), and mail the envelopes to the designated coordinator for each study site. In each sealed envelope will be a tube containing a topical solution, either the active topical nail solution or the placebo nail solution, consistent with the random number list, which will determine whether or not the placebo or active topical nail solution is contained in the tube. Each tube will be numbered in sequential numeric order from 1 to n, and recorded in the investigator’s master list, which will serve to record the random allocation code, detailing whether or not the placebo nail solution or the active topical nail solution was dispensed in the designated tube dispensed to each volunteer participant enrolled. Each tube will be labelled with the alphanumeric designation that denotes the distinct study site (A to J), and the distinct participant (1, 2, 3,…n). The labeled tubes will be mailed to the study sites in blocks of 10, and replenished based on the prevalence of enrolment at each site. At each study site, the investigator will open, in sequential numeric order, a sealed envelope and dispense the labeled tube to the eligible participant in consecutive order. Neither the study doctors responsible for enrolling and assessing the participants, nor the participants themselves, will know which of the treatment groups the participant will be in. The nail solution with its labelled envelope will be stored in a secure location at each site investigator’s office. The topical antifungal medication under investigation is Tolcylen™. It will be provided by Marlinz Pharma, Houston, TX, the study funding Sponsor. The topical therapy will be applied in accordance with the existing FDA-approved method for the use of this cosmetic agent. Administration of the interventions, active and placebo, will continue for no longer than nine (9) months. Administration of the topical agent may stop sooner if clinical and mycological evidence of cures are identified prior to nine (9) months. Participants in the control group will apply a placebo topical solution to the involved toe nail/s. Preparation of the placebo solution, dimethicone 5%, was undertaken with the aim of making it as close as possible to the active topical nail solution in terms of color and texture, and other physical characteristics. The placebo nail solution, like the active topical nail solution, meets the FDA’s safe ingredient criteria for an over-the-counter topical agent. The placebo, like the active topical nail solution, will be supplied in three (3) 7.5 ml tubes with a controlled-release applicator mechanism that allows a thin coat of the solution to be applied at a time, and the instructions for application specify that only a thin coat of solution to be applied daily to under the leading edge, borders of the toenail and the entire surface of the toenail. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Therapeutic effect |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Tolcylen™ |
| Primary outcome measure | Mycological presence or absence of fungal hyphae detected using Periodic Acid-Schiff (PAS) stain of toenail fragments at baseline, 3, 7 and 9 months |
| Secondary outcome measures | 1. Quality of life measured using ONYCOE-t™ quality of life outcome score at baseline, 3, 7 and 9 months 2. Clinical appearance of an involved toenail assessed using the Visible Nail Plate Involvement Score at baseline, 3, 7 and 9 months |
| Overall study start date | 10/04/2019 |
| Overall study end date | 01/10/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 100 Years |
| Sex | Both |
| Target number of participants | 70 |
| Participant inclusion criteria | 1. Male or female participants aged 18 years or older 2. If female is of childbearing potential, she must not be pregnant at the time of enrollment and she must be using an accepted form of birth control during the study treatment period (acceptable forms include: post-menopausal, surgical sterility, complete abstinence, sterilized sexual partner, tubal occlusion, copper-T intrauterine device, levonorgestrel-releasing intrauterine device, medroxyprogesterone injections, etonogestrel implants, combined pills, norelgestromin/ethinyl estradiol transdermal system, intravaginal device, or Cerazette pill; and for males the use of a condom with spermicide or surgical sterility) 3. Participant has a diagnosis of onychomycosis diagnosed by means of history, physical examination, and positive (evidence of fungal hyphae) mycological tissue examination by periodic acid-Schiff (PAS) staining 4. At least one toenail with distal subungual involvement, localized to any toe, with at least 10% involvement and including up to 100% involvement of the visible nail plate, any nail plate thickness, with the index nail being the most involved per inspection by the on-site investigator and agreed upon by the designated co-investigator study doctor (Hye Kim, DPM), who will inspect specific clinical photographs of the involved nail/s (the photographs will be obtained at each study site using a specified method, as demonstrated to site investigators, so that the clinical features are appropriately demonstrated) 5. Participant has an intact protective cutaneous sensation as measured with the Ipswich test for loss of protective sensation (10-gram monofilament) 6. Participant has an intact cutaneous barrier, with or without the presence of hyperkeratotic lesions, with or without concomitant tinea pedis or interdigital maceration, or with or without a history of previous skin ulceration, but without active or current pedal ulceration 7. Participant must be a satisfactory candidate for the proposed topical antifungal or placebo intervention 8. Participant must display the ability to understand and give informed consent to participation, on a voluntary basis, in the research study |
| Participant exclusion criteria | 1. Presence of dermatophytoma, defined as thick masses of fungal hyphae and necrotic keratin between the nail plate and nail bed 2. Use of any systemic antifungal therapeutic agents within 7 months before the baseline visit, or topical antifungal agent on the feet within 1 month preceding the baseline measurement visit 3. Candidate with moccasin tinea pedis involving greater than 50% of either plantar surface 4. Candidate requires the use of narcotic analgesic or non-steroidal anti-inflammatory drug/s for 48 hours prior to baseline visit or at any follow-up clinical evaluations 5. Candidate has an active drug/alcohol dependence or abuse history 6. Candidate has a loss of protective pedal sensation or open cutaneous compromise involving the ipsilateral foot 7. Candidate has trauma to the nail that resulting in permanent nail plate discoloration or shape 8. Candidate displays radiographic evidence of abnormal lytic or proliferative bone lesion in the toe/s of interest, including recent or healing of an acute fracture, if clinical inspection indicates the potential presence of subungual exostosis (radiographs will be obtained and paid for in the course of usual and customary care, outside of participation in this study) 9. Candidate has had previous nail matrix ablative surgery, either chemical or cold steel, on any of the involved digits 10. Candidate presents systemic or local contraindications to the proposed application of the topical antifungal nail solution or the placebo agent, such as an uncontrolled cardiac, neurological, hepatic, renal, metabolic, or hematological disease or impairment that has been identified 11. Candidate suffers from malignant, or bacterial or viral infectious cause/s of nail plate dystrophy 12. Candidate shows signs of substantial peripheral circulatory insufficiency 13. Candidate is currently participating in another surgical, device, or drug study or has participated in any research study involving an investigational device or drug, or surgical procedure, within the preceding 30 days 14. Candidate is allergic to any of the study products 15. Candidate is unwilling or unable to comply with the study procedures 16. Candidate is affiliated with the investigator or persons working at a study site, or patient who is an employee of the sponsor’s company 17. Candidate is institutionalized because of legal or regulatory order 18. Candidate is unable to provide informed consent to voluntarily participate in clinical research. |
| Recruitment start date | 25/08/2021 |
| Recruitment end date | 31/07/2024 |
Locations
Countries of recruitment
- United States of America
Study participating centres
Douglasville, Georgia
31533
United States of America
St Cloud, Minnesota
56303
United States of America
Potomac, Maryland
20854
United States of America
Valatie, New York
12184
United States of America
Las Vegas, Nevada
89135
United States of America
Fort Collins, Colorado
80526
United States of America
Augusta, Georgia
30909
United States of America
Brownsville, Texas
78526
United States of America
Sponsor information
Industry
15115 Park Row, Suite 100
Houston, Texas
77084
United States of America
| Phone | +1 (0)844 398 5656 |
|---|---|
| info@marlinzpharma.com | |
| Website | info@marlinzpharma.com |
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 01/12/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Stored in non-publicly available repository, Data sharing statement to be made available at a later date |
| Publication and dissemination plan | After completion of data collection and analysis, a report of the results will be prepared for submission to a peer-reviewed journal for consideration for publication. |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Other files | Case report forms, consent forms, other files | 12/08/2024 | No | No | |
| Protocol file | 01/07/2019 | 12/08/2024 | No | No | |
| Statistical Analysis Plan | 12/08/2024 | No | No | ||
| Dataset | Excel file | 22/01/2025 | No | No | |
| Other files | OnyCOE form | 22/01/2025 | No | No | |
| Other files | VNPIS form | 22/01/2025 | No | No |
Additional files
- ISRCTN77852934 SAP.pdf
- ISRCTN77852934 Protocol 01July2019.pdf
- ISRCTN77852934.zip
- Case report forms, consent forms, other files
- ISRCTN77852934 Final Dataset ISRCTN.xlsx
- Excel file
- ISRCTN77852934 OnyCOE Form.pdf
- OnyCOE form
- ISRCTN77852934 VNPIS Form Used.pdf
- VNPIS form
Editorial Notes
22/01/2025: The following changes were made to the trial record:
1. A dataset was uploaded as an additional file.
2. Forms used in the study were uploaded as additional files.
12/08/2024: The following changes were made to the trial record:
1. The statistical analysis plan was uploaded as an additional file.
2. Uploaded protocol (not peer-reviewed) as an additional file.
3. A zipped folder of other files was uploaded as an additional file.
18/07/2024: Study's existence confirmed by WCG IRB.
