Secretome TGF Beta 3

NCT07137130 | Not Yet Recruiting

• 1 other identifier: TGF B3
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

A therapeutic modality currently being developed for melasma is secretome. Secretome is a bioactive molecule secreted by mesenchymal stem cells in a conditioned medium containing a large number of growth factors, cytokines, various macromolecules, and extracellular vesicles, including microvesicles and exosomes, that can stimulate various biological reactions, particularly in modulating new tissue formation. Secretome can provide a depigmenting effect by increasing the proliferation and migration of epidermal keratinocytes, which contain melanin pigment, in line with increased fibroblast synthesis. Secretomes contain various cytokines and growth factors, one of which is transforming growth factor (TGF)-β. TGF-β is primarily secreted by fibroblasts (FB) and, to a lesser extent, by keratinocytes, and plays a crucial role in regulating melanocyte function. TGF-β has been reported to inhibit cAMP/protein kinase A signaling and induce GLI2, which then suppresses microphthalmia-associated transcription factor (MITF), a central transcription factor in melanogenesis. A study by Moon et al. in Korea examined TGF-β3. Moon et al. examined the effects of TGF-β3 on melanogenesis in human melanocytes co-cultured with skin cells irradiated with ultraviolet (UV) light, and in UV-irradiated human skin. The results showed that UVB irradiation or stem cell factor (SCF)/endothelin-1 (ET-1) increased melanogenesis. TGF-β3 effectively inhibited melanin accumulation and tyrosinase activity by downregulating the extracellular signal-regulated kinase (ERK)/microphthalmia-associated transcription factor (MITF) pathway. TGF-β3 increased the expression of keratinocyte differentiation markers. Mechanistically, TGF-β3 inhibits melanogenesis by inhibiting MITF expression, which is regulated by ERK. TGF-β1 reduces MITF but at the risk of inducing skin fibrosis. However, in the study by Moon et al., the aforementioned TGF Beta 1 function was not found in TGF-β3. Furthermore, TGF-β3 restored skin differentiation function in UV-irradiated keratinocytes. To date, there have been no clinical trials comparing intradermal injection of concentrated secretome with intradermal injection of concentrated secretome with the addition of TGF-β3 as a melasma therapy in Indonesia, thus encouraging researchers to conduct further research.

Conditions

Melasma

Outcome Measures

Primary Outcomes (6)

• Change of Melasma Severity based on Patient's Tolerability Assesment (PtGA).

  one method of evaluating the response to therapy in melasma which is assessed subjectively by the patient. The response to therapy can be assessed as follows No or slight response: \< 25% improvement Moderate response: 25% - 50% improvement Good response: 50% improvement - \< 75% Excellent response: improvement \> 75% The response is said to be good if the score is above 50% since the previous visit

  re-evaluation on day 14, 28, 42, 56 and day 84 of therapy

• Change of Melasma Severity based on modified Melasma Severity Index (mMASI) score

  The range of values for mMASI is between 0 and 24 which can then be divided into mild melasma (0-8), moderate (8-16), and severe (16-24). improvement occurs if the mMASI score decreases by \<50% from the previous visit worsening if score persists or mMASI Score Increase \>50% re-evaluation on day 14, 28, 42, 56 and day 84 of therapy

  re-evaluation on day 14, 28, 42, 56 and day 84 of therapy

• Change of Melasma Severity based on Dermoscopy

  based on Dermoscopy Telangiectasis score assessment using a 5-point dermoscopy-scale: 0 = No visible capillaries. 1 = Elongated capillaries accompanied by dilation, not visible to the naked eye. 2 = Moderate telangiectasis that is beginning to be visible to the naked eye. 3 = Severe telangiectasis characterized by reduced capillary loops. 4 = Very severe telangiectasis characterized by dilatation and loss of capillary loops.

  re-evaluation on day 84 of therapy

• Change of Melasma Severity based on Wood's Lamp

  Epidermal Type/ Dermal Typed/ Mixed Typed

  re-evaluation on day 84 of therapy

• Change of Melanin Index Based on Mexameter

  improves if there is a decrease in melanin levels \> 50% from the initial visit It is said to be bad or persistent if there is no decrease in melanin levels or there is a decrease of \<50%

  re-evaluation on day 14, 28, 42, 56 and day 84 of therapy

• Change of Erytema Index Based on Mexameter

  improves if there is a decrease in Erytema levels \> 50% from the initial visit It is said to be bad or persistent if there is no decrease in erythema levels or there is a decrease of \<50%

  re-evaluation on day 14, 28, 42, 56 and day 84 of therapy

Study Arms (2)

Secretome raw material group

EXPERIMENTAL

Group A, the treatment group, used Secretome (raw material) 3ml Intradermal injection, Sunscreen in the morning and used Tretinoin cream 0,05% at night and cleanser which was used in the morning and evening before using the cream.

Drug: Concentrated secretome Injection 3 mL; Drug: Concentrated secretome Injection 3 mL with addition of TGF Beta 3

Secretome raw material with addition of TGF Beta 3 group

EXPERIMENTAL

Group B, the treatment group, used Secretome (raw material) 3ml with addition of TGF Beta 3 Intradermal injection, Sunscreen in the morning and used Tretinoin cream 0,05% at night and cleanser which was used in the morning and evening before using the cream.

Drug: Concentrated secretome Injection 3 mL; Drug: Concentrated secretome Injection 3 mL with addition of TGF Beta 3

Interventions

Concentrated secretome Injection 3 mL DRUG

The secretome used in this research comes from mesenchymal stem cells from adipose tissue produced by Dr. Cipto Mangunkusumo Hospital Stem Cell Medical Technology. The secretome produced by mesenchymal stem cells is collected, centrifuged to separate it from debris, and followed by filtration with a 0.22 μm pore filter to ensure sterility. Next, the concentration process is carried out using tangential flow filtration with the Spin-X UF 500® concentrator, packaged, and stored at -80 degrees Celsius. The product used is a sterile product, which is tested for sterility and total protein content. When it is to be used, the secretome is removed from the freezer, warmed (thawing), and injected into the patient according to a predetermined method.

Secretome raw material group; Secretome raw material with addition of TGF Beta 3 group

Concentrated secretome Injection 3 mL with addition of TGF Beta 3 DRUG

The secretome used in this research comes from mesenchymal stem cells from adipose tissue produced by Dr. Cipto Mangunkusumo Hospital Stem Cell Medical Technology. The secretome produced by mesenchymal stem cells is collected, centrifuged to separate it from debris, and followed by filtration with a 0.22 μm pore filter to ensure sterility. Next, the concentration process is carried out using tangential flow filtration with the Spin-X UF 500® concentrator, packaged, and stored at -80 degrees Celsius. The product used is a sterile product, which is tested for sterility and total protein content. When it is to be used, the secretome is removed from the freezer, warmed (thawing), and injected into the patient according to a predetermined method after the secretome is ready, TGF beta 3 will be added to secretome

Secretome raw material group; Secretome raw material with addition of TGF Beta 3 group

Eligibility Criteria

• Age: 30 Years - 60 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Women diagnosed with melasma.
• Women without melasma and have areas of skin that are clinically free of lesions for SP control.
• years old.
• Fitzpatrick skin type IV-V.
• Willing to be a research subject by signing a research consent form (Informed Consent).

You may not qualify if:

• Pregnant and breastfeeding women.
• Currently using hormonal contraception or have ever used contraception hormones in the last 6 months.
• Using topical therapy for melasma, for example corticosteroids, tretinoin, hydroquinone, and other therapies that whiten or brighten the skin in the last 2 weeks.
• Using topical triple combination cream therapy for at least 3 months and did not show significant improvement
• Using systemic therapy for melasma, for example antioxidants or tranexamic acid in the last 4 weeks.
• History of superficial peeling therapy in the last 4 weeks.
• History of deep peeling therapy, laser or mechanical abrasion in the last 6 months.
• Using drugs that are photosensitizers such as tetracycline, phenytoin, carbamazepine, spironolactone.
• History of blood clotting disorders or on blood thinning therapy.
• Allergy to tranexamic acid.
• Have other skin complaints that may interfere with the evaluation of melasma, for example post-inflammatory hyperpigmentation, Hori's nevus, Ota's nevus, pigmented contact dermatitis, and other pigmentation disorders
• Difficulty complying with treatment.

Sponsors & Collaborators

• Indonesia University: lead

Study Sites (1)

Dr. Cipto Mangunkusumo Hospital

Central Jakarta, D.k.i Jakarta, 10430, Indonesia

Location

Related Publications (1)

• Moon HR, Jung JM, Kim SY, Song Y, Chang SE. TGF-beta3 suppresses melanogenesis in human melanocytes cocultured with UV-irradiated neighboring cells and human skin. J Dermatol Sci. 2020 Aug;99(2):100-108. doi: 10.1016/j.jdermsci.2020.06.007. Epub 2020 Jun 24.

  PMID: 32620316 BACKGROUND

MeSH Terms

Conditions

Melanosis

Condition Hierarchy (Ancestors)

Hyperpigmentation; Pigmentation Disorders; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

Prof. Dr. dr. Irma Bernadette S. Sitohang, Sp.DVE, Subsp.DKE IBSS Irma IBSS M.D, Ph.D, M.D, Ph.D

CONTACT

+62818130761; irma_bernadette@yahoo.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. M.D, Ph.D (Principal Investigator and Clinical Professor)

Study Record Dates

• First Submitted: August 6, 2025
• First Posted: August 22, 2025
• Study Start: February 14, 2026
• Primary Completion (Estimated): May 14, 2026
• Study Completion (Estimated): December 20, 2026
• Last Updated: August 22, 2025

Record last verified: 2025-08

Locations

ID (1)