Various Therapies for Central Centrifugal Alopecia

(CCCA Trial)

Overseen By Judy Holbrook, CRC

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: Wake Forest University Health Sciences

Must not be taking: Topical steroids, Minoxidil

Disqualifiers: Other hair loss, Inflammatory scalp disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 12

Duration: 8 months

250 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have used topical treatments for CCCA in the past 4 months or long-term oral antibiotics for hair loss in the past year.

What data supports the effectiveness of the drug triamcinolone acetonide for treating central centrifugal alopecia?

Triamcinolone acetonide is a corticosteroid known for its anti-inflammatory properties and is used in various skin conditions. Its long-lasting effects and unique binding mechanisms may contribute to its effectiveness in dermatologic diseases, although specific data for central centrifugal alopecia is not provided. ^{1 2 3 4 5}

Is the treatment for central centrifugal alopecia generally safe for humans?

Topical corticosteroids, like triamcinolone acetonide, have been shown to be effective and generally well-tolerated in treating skin conditions, though they can cause local side effects like skin thinning. Safety data from various studies suggest that while these treatments are effective, they should be used with caution to avoid potential adverse effects. ^{6 7 8 9 10}

How does the drug combination of Doxycycline, Minoxidil, and Triamcinolone Acetonide differ from other treatments for central centrifugal alopecia?

This drug combination is unique because it combines an antibiotic (Doxycycline), a hair growth stimulant (Minoxidil), and a potent anti-inflammatory steroid (Triamcinolone Acetonide) to address both the inflammatory and hair loss aspects of central centrifugal alopecia, whereas other treatments may focus on only one aspect. ^{11 12 13 14 15}

What is the purpose of this trial?

The objective of this study is to examine photos of CCCA patients taken before and after treatment to compare treatment outcomes between different treatment groups

Research Team

Amy McMichael, MD

Principal Investigator

Wake Forest Baptist Health Department of Dermatology

Eligibility Criteria

This trial is for African-American women aged 18-60 with a specific type of hair loss called CCCA, confirmed by clinical diagnosis and biopsy. They must have a certain level of disease severity but haven't had multiple steroid scalp injections or long-term oral antibiotics for hair loss in the past year. Those who've used topical treatments for CCCA recently are also excluded.

Inclusion Criteria

I have CCCA with a severity level between 1 and 4.

I am an African-American woman, aged 18-60, with a confirmed CCCA diagnosis and mild to moderate scalp hair loss.

I am an African-American woman aged between 18 and 60.

Exclusion Criteria

I have not had more than two steroid injections in my scalp in the last year.

I have not taken long-term antibiotics for hair loss in the past year.

I only have CCCA as my form of hair loss.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either topical steroid plus oral antibiotic or topical steroid plus intralesional steroid, followed by topical minoxidil after 8 months

8 months

Monthly visits for treatment monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Visits at Month 12 and Month 18-20

Treatment Details

Interventions

• Doxycyline
• Minoxidil
• Topical steroid class I-II
• Triamcinolone Acetonide

Trial Overview The study compares the effectiveness of different treatments on CCCA: Triamcinolone Acetonide (a steroid), class I-II topical steroids, Minoxidil (hair growth medication), and Doxycycline (an antibiotic). Patients' scalp photos before and after treatment will be used to assess results.

Participant Groups

Group I: Topical steroid plus intralesional steroid injection group Active Control 3 Interventions

Participants in this group receive topical steroid (class I-II applied once daily) plus intralesional steroid group (7.5mg/cc of kenaolog, max dose of 3 cc), and then topical minoxidil (5% solution or foam) after 8 months of treatment

Group II: Topical steroid plus oral antibiotic group Active Control 3 Interventions

Participants in this group receive topical steroid (class I-II applied once daily) plus oral antibiotic group (doxycyline 100 mg twice daily for 6 months), and then topical minoxidil (5% solution or foam) after 8 months of treatment.

Doxycyline is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Doxycycline for:

• Bacterial infections
• Severe acne
• Rosacea
• Malaria prevention
• Anthrax infection

Approved in European Union as Doxycycline for:

• Bacterial infections
• Severe acne
• Rosacea
• Malaria prevention
• Anthrax infection

Approved in Canada as Doxycycline for:

• Bacterial infections
• Severe acne
• Rosacea
• Malaria prevention
• Anthrax infection

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

The Skin of Color Society

Collaborator

Trials

1

Recruited

250+

Findings from Research

Intramuscular triamcinolone acetonide (Kenalog®) has a unique ability to provide long-lasting anti-inflammatory effects, making it distinct from other corticosteroids, which may be due to its low solubility in blood and slow absorption rate.

The efficacy of triamcinolone acetonide at low doses for treating dermatologic diseases suggests that its mechanism of action involves complex binding properties and metabolic pathways that are not yet fully understood, indicating potential for further research in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enigma of Intramuscular Triamcinolone Acetonide (Kenalog®) Efficacy. Shahinfar, S., Maibach, H.[2023]

Intralesional Kenalog (triamcinolone) is an effective treatment for skin conditions like nodulocystic acne, demonstrating its therapeutic potential.

However, this case highlights a rare but significant side effect: a granulomatous reaction, indicating that while the treatment is beneficial, it can also lead to adverse histopathological responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Granulomatous Reaction to Intralesional Kenalog (Triamcinolone) Injection in Acne: A Case Report. Song, Y., Guo, Y.[2020]

In a study of 31 eyes from 30 patients, subconjunctival injections of triamcinolone acetonide significantly improved visual acuity and reduced central macular thickness over 12 months, indicating its efficacy in treating uveitic macular edema.

The treatment was found to be safe, with no significant increase in intraocular pressure and only one cataract diagnosed, which occurred in an uninjected eye, suggesting minimal risk of adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safety and efficacy of subconjunctival triamcinolone injections in the management of uveitic macular edema: retrospective study of thirty-one cases]. Bleriot, A., Couret, C., Le Meur, G., et al.[2014]

A 24-year-old woman experienced an immediate hypersensitivity reaction to intralesional triamcinolone acetonide after 10 years of successful treatment for keloid scars, highlighting that such reactions, while uncommon, can occur even after multiple prior injections without issues.

Allergy testing confirmed a positive reaction specifically to triamcinolone acetonide, indicating that IgE-mediated hypersensitivity should be considered in patients receiving repeated injections of this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anaphylaxis following intralesional triamcinolone acetonide (Kenacort) injection. Laisuan, W., Wongsa, C., Dchapaphapeaktak, N., et al.[2020]

In a study of 64 eyes from 60 patients with non-infectious posterior uveitis, both triamcinolone acetonide and methylprednisolone acetate showed similar efficacy in improving symptoms after 6 weeks, with no significant difference in improvement rates.

However, triamcinolone treatment was associated with side effects such as prolonged upper lid ptosis and increased intraocular pressure, which were not observed in patients treated with methylprednisolone, suggesting that methylprednisolone may be a safer option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical trial to compare efficacy and side-effects of injection of posterior sub-Tenon triamcinolone versus orbital floor methylprednisolone in the management of posterior uveitis. Ferrante, P., Ramsey, A., Bunce, C., et al.[2016]

Hydrocortisone and its non-halogenated double-ester derivatives are less toxic to skin cells compared to conventional medium potency topical glucocorticoids like betamethasone valerate, suggesting a safer option for treating inflammatory skin diseases.

The study utilized an in vitro assay with human keratinocytes and fibroblasts to assess the cytotoxic effects of various glucocorticoids, revealing that hydrocortisone aceponate had significantly lower toxicity than betamethasone valerate, indicating potential for better local tolerance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discrimination of the toxic potential of chemically differing topical glucocorticoids using a neutral red release assay with human keratinocytes and fibroblasts. Korting, HC., Hülsebus, E., Kerscher, M., et al.[2019]

Amcinonide cream was classified as a very strong corticosteroid, while prednicarbate cream was found to be moderately strong, based on a series of tests including the vasoconstriction test conducted on healthy young individuals.

The vasoconstriction test proved to be an effective screening method for determining the potency of corticosteroid preparations, with results largely consistent across various other tests, although clinical evaluations are recommended for further validation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Comparative evaluation of the potencies of external corticoids with various test methods]. Koch, EM., Ott, R.[2016]

The study tested the common belief that higher concentrations of topical corticosteroids lead to greater biological activity using a vasoconstriction assay, which is linked to clinical effectiveness.

Results showed that for many brand-name formulations, higher concentrations do not always correlate with increased efficacy, indicating that the effectiveness of topical corticosteroids can vary significantly even among different concentrations of the same medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The same glucocorticoid in brand-name products. Does increasing the concentration result in greater topical biologic activity? Stoughton, RB., Wullich, K.[2010]

Cutivate was found to be the best topical corticosteroid cream among six evaluated, excelling in stiffness, grittiness, color, odor, homogeneity, pH, weight loss, and tackiness.

The other creams, including Elocon, Westcort, Lidex, and Kenalog, had similar properties to each other but were overall less favorable than Cutivate, while Valisone was rated lower due to its strong odor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of cosmetic and physicochemical properties of six topical corticosteroid creams. Hadzija, BW., Ambrose, WW.[2016]

Diflucortolone valerate (0.1%) has demonstrated good efficacy and tolerability in treating inflammatory and allergic skin conditions across multiple trials involving over 8,600 patients in Southeast Asia, with a rapid onset of effect.

In combination with other agents, such as chlorquinaldol and isoconazole nitrate, diflucortolone valerate showed superior efficacy in treating skin infections and conditions compared to standard treatments, confirming its value in dermatological practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diflucortolone valerate. Asian experience. Hoppe, G.[2022]

Terbinafine is the most effective systemic treatment for onychomycosis and is also safe for use in children, making it a preferred choice for dermatophyte infections.

For tinea capitis, terbinafine, itraconazole, and fluconazole are effective against Trichophyton species, while griseofulvin is recommended for Microsporum infections, highlighting the importance of species-specific therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mycology - an update Part 3: Dermatomycoses: topical and systemic therapy. Nenoff, P., Krüger, C., Paasch, U., et al.[2015]

Oral terbinafine, along with itraconazole and fluconazole, became a key systemic treatment option for onychomycosis starting in 1996, providing effective management for this fungal nail infection.

The introduction of topical treatments like efinaconazole and tavaborole in 2014 offered additional options for patients who may not be able to use systemic antifungals due to other health conditions or personal preferences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antifungal Drugs for Onychomycosis: Efficacy, Safety, and Mechanisms of Action. Rosen, T., Stein Gold, LF.[2018]

Oral antifungal treatments, such as itraconazole and terbinafine, are essential for extensive or chronic dermatophyte infections, while topical treatments are effective for localized infections like tinea corporis and tinea pedis.

New topical options like amorolfine and ciclopirox are now available for treating milder cases of onychomycosis, but patient education on hygiene and proper follow-up is crucial to prevent relapse of infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update in antifungal therapy of dermatophytosis. Gupta, AK., Cooper, EA.[2021]

A study evaluated the in vitro effectiveness of 11 antifungal drugs against Trichophyton verrucosum isolates from humans and animals, revealing that ciclopirox showed the strongest antifungal activity, while fluconazole had the weakest effect.

All tested drugs demonstrated satisfactory antifungal activity, with MICs for clotrimazole, ciclopirox, enilconazole, miconazole, naftifine, and terbinafine being below 1 μg/mL, suggesting they are promising candidates for treating T. verrucosum infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of in vitro activities of 11 antifungal agents against Trichophyton verrucosum isolates associated with a variety hosts and geographical origin. Łagowski, D., Gnat, S., Nowakiewicz, A., et al.[2020]

Itraconazole and terbinafine, two newer oral antifungal agents, allow for shorter and more effective treatment courses for onychomycosis compared to older oral agents, with both showing comparable efficacy against dermatophyte infections.

These newer antifungals have a favorable safety profile and are also effective against other fungal infections like tinea capitis and tinea versicolor, often requiring shorter treatment regimens than traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Management of Onychomycosis and Dermatomycoses. Del Rosso JQ, .[2020]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Enigma of Intramuscular Triamcinolone Acetonide (Kenalog®) Efficacy. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Granulomatous Reaction to Intralesional Kenalog (Triamcinolone) Injection in Acne: A Case Report. [2020]

3. France pubmed.ncbi.nlm.nih.gov

[Safety and efficacy of subconjunctival triamcinolone injections in the management of uveitic macular edema: retrospective study of thirty-one cases]. [2014]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Anaphylaxis following intralesional triamcinolone acetonide (Kenacort) injection. [2020]

5. Australia pubmed.ncbi.nlm.nih.gov

Clinical trial to compare efficacy and side-effects of injection of posterior sub-Tenon triamcinolone versus orbital floor methylprednisolone in the management of posterior uveitis. [2016]

6. England pubmed.ncbi.nlm.nih.gov

Discrimination of the toxic potential of chemically differing topical glucocorticoids using a neutral red release assay with human keratinocytes and fibroblasts. [2019]

7. Germany pubmed.ncbi.nlm.nih.gov

[Comparative evaluation of the potencies of external corticoids with various test methods]. [2016]

8. United States pubmed.ncbi.nlm.nih.gov

The same glucocorticoid in brand-name products. Does increasing the concentration result in greater topical biologic activity? [2010]

9. United States pubmed.ncbi.nlm.nih.gov

Comparison of cosmetic and physicochemical properties of six topical corticosteroid creams. [2016]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Diflucortolone valerate. Asian experience. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

Mycology - an update Part 3: Dermatomycoses: topical and systemic therapy. [2015]

12. United States pubmed.ncbi.nlm.nih.gov

Antifungal Drugs for Onychomycosis: Efficacy, Safety, and Mechanisms of Action. [2018]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Update in antifungal therapy of dermatophytosis. [2021]

14. Germany pubmed.ncbi.nlm.nih.gov

Comparison of in vitro activities of 11 antifungal agents against Trichophyton verrucosum isolates associated with a variety hosts and geographical origin. [2020]

15. United States pubmed.ncbi.nlm.nih.gov

Current Management of Onychomycosis and Dermatomycoses. [2020]