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Trial registered on ANZCTR


Registration number
ACTRN12622000522718p
Ethics application status
Not yet submitted
Date submitted
20/03/2022
Date registered
1/04/2022
Date last updated
17/04/2023
Date data sharing statement initially provided
1/04/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Comparison of the efficacy of two triple therapy topical combinations in the treatment of melasma
Scientific title
Comparison of the efficacy of two triple therapy topical combinations in the treatment of melasma in adults
Secondary ID [1] 306255 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melasma 325668 0
Condition category
Condition code
Skin 323018 323018 0 0
Dermatological conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Combination topical therapy of:
1. Thiamidol 100g
2. Retinoic acid 0.05%, 0.1g
3. Dexamethasone acetate 0.1%, 0.1g
Patients will be instructed to apply a pea-sized (approximately 2mL) amount of the combination product across their entire face every night for 12 consecutive weeks. Patients will also be instructed to apply a teaspoon amount of SPF 50 sunscreen 3 times a day for the same treatment period as well as 12 weeks after cessation of the combination therapy while the skin is expected to remain photosensitive due to the residual effects of treatment.
Medication adherence will be evaluated at the end of the 12-week treatment period by assessing the amount of remaining product.
Intervention code [1] 323149 0
Treatment: Drugs
Comparator / control treatment
Combination topical therapy of:
1. Hydroquinone 5%, 5g
2. Retinoic acid 0.1%, 0.1g
3. Dexamethasone acetate 0.1%, 0.1g
4. Excipial hydro 100g
This combination is commonly referred to as the 'Kligman's Trio' or 'Kligman's formula' and is the current gold standard treatment for melasma. Patients will be instructed to apply a pea-sized (approximately 2mL) amount of the combination product across their entire face every night for 12 consecutive weeks. Patients will also be instructed to apply a teaspoon amount of SPF 50 sunscreen 3 times a day for the same treatment period as well as 12 weeks after cessation of the combination therapy while the skin is expected to remain photosensitive due to the residual effects of treatment.
Medication adherence will be evaluated at the end of the 12-week treatment period by assessing the amount of remaining product.
Control group
Active

Outcomes
Primary outcome [1] 330786 0
Treatment efficacy, measured using the modified melasma area and severity index (mMASI) score.
Timepoint [1] 330786 0
Assessed after 12 weeks of treatment (week 12) and 12 weeks after treatment cessation (week 24), comparing to mMASI score at baseline (measured at week 0).
Secondary outcome [1] 407553 0
Tolerance, as assessed using a visual scale ranging from 0 to 10 quantifying the degree of erythema, dry skin, irritation and flaking. The component scores will be assessed as a composite outcome.
Timepoint [1] 407553 0
Assessed after 12 weeks of treatment (week 12) and 12 weeks after treatment cessation (week 24).
Secondary outcome [2] 407554 0
Effectiveness, measured by colorimetric evaluation of skin pigmentation changes in lesional and perilesional skin. A mexameter will be used for this.
Timepoint [2] 407554 0
Assessed after 12 weeks of treatment (week 12), and 12 weeks after cessation of treatment (week 24), comparing to colorimetry score at baseline (measured at week 0).
Secondary outcome [3] 407555 0
Quality of life, as assessed using the Melasma Quality of Life (MELASQOL) self-questionnaire.
Timepoint [3] 407555 0
Assessed after 12 weeks of treatment (week 12), and 12 weeks after cessation of treatment (week 24), comparing to MELASQOL score at baseline (measured at week 0).
Secondary outcome [4] 407556 0
Overall patient perception of products, as evaluated through the question "have the products you have used to improve your melasma reduced its severity" with a 5-point Likert scale answer option ranging from strongly agree to strongly disagree.
Timepoint [4] 407556 0
Assessed after 12 weeks of treatment (week 12).

Eligibility
Key inclusion criteria
- Patient clinically diagnosed with melasma
- If patient is of childbearing age, she will be required to use a reliable contraceptive for at least 1 month and agree not to change her contraceptive status for the duration of the study
- Patient who has signed the written informed consent form for study participation
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Women who are pregnant or breast-feeding or who are planning for pregnancy during the course of the study. (A urine b-HCG or urine dipstick test will be performed)
- Patient with another pigmentation disorder on the face.
- Patient with other dermatoses that may interfere with the evaluation or application of the products involved in the study.
- Patient who has used a depigmentation agent in the month prior to inclusion.
- Patient who has used a local corticosteroid on the skin, eyes, nose or mouth (inhaled corticosteroid) or systemic corticosteroids during the month prior to inclusion.
- Patient who has used local tretinoin or hydroquinone in the month prior to inclusion.
- Patient on chronic anti-inflammatory therapies (patient accepted into study if cumulative NSAID use is less than 10 days over the duration of the study).
- Patient with a clinically significant history of allergy, especially to the components of the products studied.
- Vulnerable persons including people under the age of 18 and those who are unable to take care of or protect themselves against harm or exploitation.
- Patient being in a situation that, in the investigator's opinion, may interfere with optimal participation in the study.
- Patient who is participating or has participated in another clinical drug trial in the month prior to inclusion.
- Patient who cannot communicate effectively with the investigator or who cannot follow the instructions involved in the study.
- Patient who is refusing to be photographed as part of the study.
- Patient who withdraws their informed consent from the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation will take place at the off-site Atara compounding pharmacy.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/08/2023
Actual
Date of last participant enrolment
Anticipated
1/10/2023
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 310603 0
Self funded/Unfunded
Name [1] 310603 0
Michelle Rodrigues
Country [1] 310603 0
Australia
Primary sponsor type
Individual
Name
Michelle Rodrigues
Address
Chroma Dermatology: Ground Floor, suite 15/202 Jells Rd, Wheelers Hill VIC 3150
Country
Australia
Secondary sponsor category [1] 311796 0
None
Name [1] 311796 0
Address [1] 311796 0
Country [1] 311796 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 310208 0
Bellberry Limited
Ethics committee address [1] 310208 0
123 Glen Osmond Road Eastwood Adelaide
South Australia 5063
Ethics committee country [1] 310208 0
Australia
Date submitted for ethics approval [1] 310208 0
10/01/2022
Approval date [1] 310208 0
Ethics approval number [1] 310208 0

Summary
Brief summary
Melasma is a common disorder of hyperpigmentation, primarily affecting the face. It can affect all racial types but predominately affects women with darker skin types.

The exact cause of melasma is unknown, but it is thought to be due to many things including pregnancy, hormonal contraception, and sunlight. Melasma can be very difficult to treat and often frustrating for the patient and doctor with evidence showing that it may adversely affect quality of life.

The standard topical treatment for melasma that has been used since the 1970’s, is a combination agent including hydroquinone 5%, retinoic acid 0.1% and dexamethasone acetate 0.1% (commonly called “Kligman’s Trio”). Although this treatment is effective, it frequently causes skin irritation, and the hydroquinone is largely responsible for this. Hydroquinone also carries a risk of causing skin discolouration with long-term use.

Thiamidol, like hydroquinone, is a depigmentation agent. Recent studies showed that thiamidol was better than hydroquinone in treating melasma while causing fewer side effects (Arrowitz et al, Journal of Investigative Dermatology, 2019). Replacing hydroquinone with thiamidol in this readily prescribed depigmentation formula has never been studied.

Therefore, this study aims to determine if topical thiamidol + retinoic acid + dexamethasone acetate combination treats melasma as well as the standard Kligman's Trio.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 116866 0
Dr Michelle Rodrigues
Address 116866 0
Chroma Dermatology: Ground Floor, suite 15/202 Jells Rd, Wheelers Hill VIC 3150
Country 116866 0
Australia
Phone 116866 0
+61 3 85606946
Fax 116866 0
Email 116866 0
[email protected]
Contact person for public queries
Name 116867 0
Michelle Rodrigues
Address 116867 0
Chroma Dermatology: Ground Floor, suite 15/202 Jells Rd, Wheelers Hill VIC 3150
Country 116867 0
Australia
Phone 116867 0
+61 3 85606946
Fax 116867 0
Email 116867 0
[email protected]
Contact person for scientific queries
Name 116868 0
Michelle Rodrigues
Address 116868 0
Chroma Dermatology: Ground Floor, suite 15/202 Jells Rd, Wheelers Hill VIC 3150
Country 116868 0
Australia
Phone 116868 0
+61 3 85606946
Fax 116868 0
Email 116868 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
15448Study protocol    383452-(Uploaded-17-03-2022-00-13-37)-Study-related document.docx
15449Informed consent form    383452-(Uploaded-17-03-2022-00-13-50)-Study-related document.docx



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.