MelasmaPhase 4NCT03475524
USE THE SYSTEMIC METFORMIN IN MELASMA
A Phase 4 study testing MetFORMIN 1000 Mg Oral Tablet, Trichloroacetic Acid Peeling and MetFORMIN 500 Mg Oral Tablet in people with Melasma, run by Assiut University at 1 site in Egypt.
Trial summary
Melasma is a chronic and relapsing acquired dyschromia due to an increased epidermal-melanin unit activity that affects sun-exposed areas mainly in women throughout the reproductive years. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Melasma
- What is being tested?
- MetFORMIN 1000 Mg Oral Tablet, Trichloroacetic Acid Peeling and MetFORMIN 500 Mg Oral Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Apr 2019to Aug 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- All patients above 18 years old with melasma.
- With Fitzpatrick skin phototypes ranging from Type III-V will recruited.
Who cannot join
- Pregnant or nursing women.
- Current use of hormonal birth control medication or any hormonal therapy, Use of topical hydroquinone within 3 months of study, Use of topical steroids within 1 month of study, Regular use of tanning parlors and History of laser or dermabrasion to the face within 9 months of study.
- Occupation involving primarily outdoor activities.
- History of kidney dysfunction diabetic (excluded by history and laboratory), Significant cardiovascular or respiratory disease and any other systemic diseases(i.e,history of endocrine disorders).
- patients with poor wound healing, recurrent herpes labialis and current skin infection (facial warts, molluscum contagiosum, history of hypertrophic scar/keloids, active dermatosis of atopic, seborrheic or other eczematous type).
- Photosensitivity,
Trial locations and contacts
1 site in 1 country.
Egypt1 site, 1 recruiting
- Recruiting
Assuit University
Asyut, 71111
Radwa Bakr, 01119988115
sahar Ismail, saharsotohy@yahoo.com
About this study
Official title: THE METFORMIN AND TRICHLOROACETIC ACID IN TREATMENT OF MELASMA
Melasma is a chronic and relapsing acquired dyschromia due to an increased epidermal-melanin unit activity that affects sun-exposed areas mainly in women throughout the reproductive years. It is more common in women, accounting for 90% of all cases.The majority of patients are in third and fourth decades of their life. There are several risk factors that influence its appearance including genetic predisposition,exposure to heat and UV radiation, pregnancy, and exogenous hormones (such as oral contraceptives,thyroid hormones, and hormone replacement therapy). Other factors implicated are phototoxic drugs, anticonvulsant medications,and the use of certain cosmetics. Types of melasma are epidermal, dermal and mixed according to location of melanin.
Read the detailed description
Its pathogenesis is not fully understood, nevertheless there is evidence that melanogenesis in melasma differ from tanning and post-inflammatory hyperpigmentations as well as there is an involvement of the whole epidermal melanin unit in the process (not just hypertrophic melanocytes), mastocytes, fibroblast and endothelium derived cytokines, as well as there are upper dermal abnormalities different from other acquired pigmentary disorders. Patients with melasma have also been found to have higher markers of oxidative stress status.
Melasma has significant impact on patients physical health, interpersonal relationships ,social-well being and self- esteem as they refused to leave their house, felt inferior to others, and incessantly thought about their melasma being.
Melasma is often resistant to treatment and frustrating for both patients and clinician. In spite of presence of several methods for treatment of melasma exacted as, Topical compounds that include the Kligman's formula which is the triple combination of ( retinoid, hydroquinone, and steroid) and azelaic. Chemical peels (e.g., glycolic, β hydroxyl, and trichloroacetic acid )although these must be used cautiously in patients with darker skin. Laser and Light therapies represent potentially promising options for patients who are refractory to other modalities, but they also carry significant risk of worsening the disease.
Recently, some reports refer to the use of metformin in treatment of melasma. Metformin is antidiabetic drugs that was shown to exert its biological effect by decreasing cyclic adenosine phosphate , which is a well known modulator of melanin synthesis. Metformin decreased skin pigmentation in vivo with minimal side effects, suggesting a potential application of metformin in the treatment of hyperpigmentation disorders. Where the metformin was applied topically onto a mouse tail, whitening of the tail was observed. In addition, metformin decreased the epidermal level of melanin when metformin was applied to human skin punch biopsies and to reconstructed human epidermis. When melanocytes were treated with metformin, basal level of total melanin (eumelanin and pheomelanin) were reduced significantly. Also metformin blocked forskolin and alpha melanocyte-stimulating hormone which increase the levels of melanin. Metformin decrease levels of tyrosinase, tyrosinase-related protein-1 and tyrosinase-related protein-2.
- Conditions
- Melasma
- Being tested
- MetFORMIN 1000 Mg Oral Tablet, Placebos, Trichloroacetic Acid Peeling, MetFORMIN 500 Mg Oral Tablet
- Medical subject headings
- Melanosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetFORMIN 1000 Mg Oral TabletDrug
Also called Glucophage
oral tablet 1ooomg systemic metformin will be given to group
PlacebosDrug
oral placebos will be given to control beside trichloracetic acid peeling
Trichloroacetic Acid PeelingDrug
Trichloroacetic acid peeling to the three groups
MetFORMIN 500 Mg Oral TabletDrug
Also called Glucophage
oral tablet 500 mg
| Study group | Role | What they receive |
|---|---|---|
| study Metformin 1000 mg | Experimental | Not described Receives: Drug: MetFORMIN 1000 Mg Oral Tablet; Drug: Trichloroacetic Acid Peeling |
| study Metformin 500 mg | Experimental | Not described Receives: Drug: Trichloroacetic Acid Peeling; Drug: MetFORMIN 500 Mg Oral Tablet |
| control group | Placebo comparator | Not described Receives: Drug: Placebos; Drug: Trichloroacetic Acid Peeling |
What is being measured
The primary outcome is the main question the study is designed to answer.
degree of improvement of melasma
Melasma Area and Severity Index score will be calculated for patients before and after treatment to all patientsscore is calculated by multiplying the area of involvement with the square of pigmentation as given in the formula:
MSI = 0.4 (a × p 2 ) l + 0.4 (a × p 2 ) r + 0.2 (a × p 2 ) n
In the formula, "a" stands for "area of involvement," "p" for "severity of pigmentation," "l" for left face, "r" for right face, and "n" for nose.
The area involved, as well as the severity of pigmentation is scored from 0 to 4Score 0:No visible pigmentation,score 1 :rarely visible pigmentation scor e 2:mild pigmentation score3: moderate pigmentation score 4:sever pigmentation.scoringfor area of involvement less than or equal 10% area involved-scor1,11-30%-score2 ,31-60%-score3 and more than 60%-score 4
. patient will be photographed at baseline and after every two weeks interval and one month after the last session
Measured: up to 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2018
- Study start1 Apr 2019
- Primary completionAug 2021 (estimated)
- Study completionAug 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for MelasmaStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Karima Nageh, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03475524
- Sponsor's protocol ID
- MTM
- Status last verified
- Aug 2021
- First submitted
- 14 Mar 2018
- Last updated
- 3 Aug 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Handel AC, Miot LD, Miot HA. Melasma: a clinical and epidemiological review. An Bras Dermatol. 2014 Sep-Oct;89(5):771-82. doi: 10.1590/abd1806-4841.20143063.
PubMed 25184917Moubasher AE, Youssef EM, Abou-Taleb DA. Q-switched Nd: YAG laser versus trichloroacetic acid peeling in the treatment of melasma among Egyptian patients. Dermatol Surg. 2014 Aug;40(8):874-82. doi: 10.1097/DSS.0000000000000065.
PubMed 25068546Brianezi G, Handel AC, Schmitt JV, Miot LD, Miot HA. Changes in nuclear morphology and chromatin texture of basal keratinocytes in melasma. J Eur Acad Dermatol Venereol. 2015 Apr;29(4):809-12. doi: 10.1111/jdv.12453. Epub 2014 Mar 14.
PubMed 24629163Kong SH, Suh HS, Choi YS. Treatment of Melasma with Pulsed-Dye Laser and 1,064-nm Q-Switched Nd:YAG Laser: A Split-Face Study. Ann Dermatol. 2018 Feb;30(1):1-7. doi: 10.5021/ad.2018.30.1.1. Epub 2017 Dec 26.
PubMed 29386825Lehraiki A, Abbe P, Cerezo M, Rouaud F, Regazzetti C, Chignon-Sicard B, Passeron T, Bertolotto C, Ballotti R, Rocchi S. Inhibition of melanogenesis by the antidiabetic metformin. J Invest Dermatol. 2014 Oct;134(10):2589-2597. doi: 10.1038/jid.2014.202. Epub 2014 Apr 22.
PubMed 24756109Sarkar R, Arora P, Garg VK, Sonthalia S, Gokhale N. Melasma update. Indian Dermatol Online J. 2014 Oct;5(4):426-35. doi: 10.4103/2229-5178.142484.
PubMed 25396123Sheth VM, Pandya AG. Melasma: a comprehensive update: part I. J Am Acad Dermatol. 2011 Oct;65(4):689-697. doi: 10.1016/j.jaad.2010.12.046.
PubMed 21920241Sheth VM, Pandya AG. Melasma: a comprehensive update: part II. J Am Acad Dermatol. 2011 Oct;65(4):699-714. doi: 10.1016/j.jaad.2011.06.001.
PubMed 21920242Majid I, Haq I, Imran S, Keen A, Aziz K, Arif T. Proposing Melasma Severity Index: A New, More Practical, Office-based Scoring System for Assessing the Severity of Melasma. Indian J Dermatol. 2016 Jan-Feb;61(1):39-44. doi: 10.4103/0019-5154.174024.
PubMed 26955093Ismail SA, Mohamed GA, Mohamedeen KN, Sotohy RSA, Bakr RM. Does Systemic Metformin Have a Role in Treating Melasma? Dermatol Surg. 2024 Apr 1;50(4):366-371. doi: 10.1097/DSS.0000000000004092. Epub 2024 Feb 28.
PubMed 38416809
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- THE METFORMIN AND TRICHLOROACETIC ACID IN TREATMENT OF MELASMA
- ClinicalTrials.gov ID
- NCT03475524
- Acronym / sponsor ID
- MTM
- Conditions
- Melasma
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 1 Apr 2019 (actual)
- Primary completion
- Aug 2021 (estimated)
- Study completion
- Aug 2021 (estimated)
- First posted
- 23 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Melasma is a chronic and relapsing acquired dyschromia due to an increased epidermal-melanin unit activity that affects sun-exposed areas mainly in women throughout the reproductive years. It is more common in women, accounting for 90% of all cases.The majority of patients are in third and fourth decades of their life. There are several risk factors that influence its appearance including genetic predisposition,exposure to heat and UV radiation, pregnancy, and exogenous hormones (such as oral contraceptives,thyroid hormones, and hormone replacement therapy). Other factors implicated are phototoxic drugs, anticonvulsant medications,and the use of certain cosmetics. Types of melasma are epidermal, dermal and mixed according to location of melanin.
Detailed description
Its pathogenesis is not fully understood, nevertheless there is evidence that melanogenesis in melasma differ from tanning and post-inflammatory hyperpigmentations as well as there is an involvement of the whole epidermal melanin unit in the process (not just hypertrophic melanocytes), mastocytes, fibroblast and endothelium derived cytokines, as well as there are upper dermal abnormalities different from other acquired pigmentary disorders. Patients with melasma have also been found to have higher markers of oxidative stress status.
Melasma has significant impact on patients physical health, interpersonal relationships ,social-well being and self- esteem as they refused to leave their house, felt inferior to others, and incessantly thought about their melasma being.
Melasma is often resistant to treatment and frustrating for both patients and clinician. In spite of presence of several methods for treatment of melasma exacted as, Topical compounds that include the Kligman's formula which is the triple combination of ( retinoid, hydroquinone, and steroid) and azelaic. Chemical peels (e.g., glycolic, β hydroxyl, and trichloroacetic acid )although these must be used cautiously in patients with darker skin. Laser and Light therapies represent potentially promising options for patients who are refractory to other modalities, but they also carry significant risk of worsening the disease.
Recently, some reports refer to the use of metformin in treatment of melasma. Metformin is antidiabetic drugs that was shown to exert its biological effect by decreasing cyclic adenosine phosphate , which is a well known modulator of melanin synthesis. Metformin decreased skin pigmentation in vivo with minimal side effects, suggesting a potential application of metformin in the treatment of hyperpigmentation disorders. Where the metformin was applied topically onto a mouse tail, whitening of the tail was observed. In addition, metformin decreased the epidermal level of melanin when metformin was applied to human skin punch biopsies and to reconstructed human epidermis. When melanocytes were treated with metformin, basal level of total melanin (eumelanin and pheomelanin) were reduced significantly. Also metformin blocked forskolin and alpha melanocyte-stimulating hormone which increase the levels of melanin. Metformin decrease levels of tyrosinase, tyrosinase-related protein-1 and tyrosinase-related protein-2.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| study Metformin 1000 mg | Experimental | Drug: MetFORMIN 1000 Mg Oral Tablet, Drug: Trichloroacetic Acid Peeling |
| study Metformin 500 mg | Experimental | Drug: Trichloroacetic Acid Peeling, Drug: MetFORMIN 500 Mg Oral Tablet |
| control group | Placebo comparator | Drug: Placebos, Drug: Trichloroacetic Acid Peeling |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- All patients above 18 years old with melasma.
- With Fitzpatrick skin phototypes ranging from Type III-V will recruited.
Key exclusion criteria (6 listed)
- Pregnant or nursing women.
- Current use of hormonal birth control medication or any hormonal therapy, Use of topical hydroquinone within 3 months of study, Use of topical steroids within 1 month of study, Regular use of tanning parlors and History of laser or dermabrasion to the face within 9 months of study.
- Occupation involving primarily outdoor activities.
- History of kidney dysfunction diabetic (excluded by history and laboratory), Significant cardiovascular or respiratory disease and any other systemic diseases(i.e,history of endocrine disorders).
- patients with poor wound healing, recurrent herpes labialis and current skin infection (facial warts, molluscum contagiosum, history of hypertrophic scar/keloids, active dermatosis of atopic, seborrheic or other eczematous type).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetFORMIN 1000 Mg Oral TabletAlso: Glucophageoral tablet 1ooomg systemic metformin will be given to group | Drug | study Metformin 1000 mg |
| Placebosoral placebos will be given to control beside trichloracetic acid peeling | Drug | control group |
| Trichloroacetic Acid PeelingTrichloroacetic acid peeling to the three groups | Drug | control group, study Metformin 1000 mg, study Metformin 500 mg |
| MetFORMIN 500 Mg Oral TabletAlso: Glucophageoral tablet 500 mg | Drug | study Metformin 500 mg |
Primary outcome
degree of improvement of melasma
Time frame: up to 3 months
Melasma Area and Severity Index score will be calculated for patients before and after treatment to all patientsscore is calculated by multiplying the area of involvement with the square of pigmentation as given in the formula: MSI = 0.4 (a × p 2 ) l + 0.4 (a × p 2 ) r + 0.2 (a × p 2 ) n In the formula, "a" stands for "area of involvement," "p" for "severity of pigmentation," "l" for left face, "r" for right face, and "n" for nose. The area involved, as well as the severity of pigmentation is scored from 0 to 4Score 0:No visible pigmentation,score 1 :rarely visible pigmentation scor e 2:mild pigmentation score3: moderate pigmentation score 4:sever pigmentation.scoringfor area of involvement less than or equal 10% area involved-scor1,11-30%-score2 ,31-60%-score3 and more than 60%-score 4 . patient will be photographed at baseline and after every two weeks interval and one month after the last session
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2021.
- Results publication: PubMed 25184917Handel AC, Miot LD, Miot HA. Melasma: a clinical and epidemiological review. An Bras Dermatol. 2014 Sep-Oct;89(5):771-82. doi: 10.1590/abd1806-4841.20143063.
- Results publication: PubMed 25068546Moubasher AE, Youssef EM, Abou-Taleb DA. Q-switched Nd: YAG laser versus trichloroacetic acid peeling in the treatment of melasma among Egyptian patients. Dermatol Surg. 2014 Aug;40(8):874-82. doi: 10.1097/DSS.0000000000000065.
- Results publication: PubMed 24629163Brianezi G, Handel AC, Schmitt JV, Miot LD, Miot HA. Changes in nuclear morphology and chromatin texture of basal keratinocytes in melasma. J Eur Acad Dermatol Venereol. 2015 Apr;29(4):809-12. doi: 10.1111/jdv.12453. Epub 2014 Mar 14.
- Results publication: PubMed 29386825Kong SH, Suh HS, Choi YS. Treatment of Melasma with Pulsed-Dye Laser and 1,064-nm Q-Switched Nd:YAG Laser: A Split-Face Study. Ann Dermatol. 2018 Feb;30(1):1-7. doi: 10.5021/ad.2018.30.1.1. Epub 2017 Dec 26.
- Results publication: PubMed 24756109Lehraiki A, Abbe P, Cerezo M, Rouaud F, Regazzetti C, Chignon-Sicard B, Passeron T, Bertolotto C, Ballotti R, Rocchi S. Inhibition of melanogenesis by the antidiabetic metformin. J Invest Dermatol. 2014 Oct;134(10):2589-2597. doi: 10.1038/jid.2014.202. Epub 2014 Apr 22.
- Results publication: PubMed 25396123Sarkar R, Arora P, Garg VK, Sonthalia S, Gokhale N. Melasma update. Indian Dermatol Online J. 2014 Oct;5(4):426-35. doi: 10.4103/2229-5178.142484.
- Results publication: PubMed 21920241Sheth VM, Pandya AG. Melasma: a comprehensive update: part I. J Am Acad Dermatol. 2011 Oct;65(4):689-697. doi: 10.1016/j.jaad.2010.12.046.
- Results publication: PubMed 21920242Sheth VM, Pandya AG. Melasma: a comprehensive update: part II. J Am Acad Dermatol. 2011 Oct;65(4):699-714. doi: 10.1016/j.jaad.2011.06.001.
- Results publication: PubMed 26955093Majid I, Haq I, Imran S, Keen A, Aziz K, Arif T. Proposing Melasma Severity Index: A New, More Practical, Office-based Scoring System for Assessing the Severity of Melasma. Indian J Dermatol. 2016 Jan-Feb;61(1):39-44. doi: 10.4103/0019-5154.174024.
- Derived from this study: PubMed 38416809Ismail SA, Mohamed GA, Mohamedeen KN, Sotohy RSA, Bakr RM. Does Systemic Metformin Have a Role in Treating Melasma? Dermatol Surg. 2024 Apr 1;50(4):366-371. doi: 10.1097/DSS.0000000000004092. Epub 2024 Feb 28.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing MetFORMIN 1000 Mg Oral Tablet, Trichloroacetic Acid Peeling and MetFORMIN 500 Mg Oral Tablet in people with Melasma, run by Assiut University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sahar Ismail, professor (01007074449, saharsotohy@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
degree of improvement of melasma (time frame: up to 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03475524, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2021.