The Influence of Peripheral Androgen Conversion at Women Adult Acne

Quality of Life Clinical Trial

Official title:

The Influence of Peripheral Androgen Conversion at Toll-like Receptors-2 and CD1d Expressions in Human Keratinocytes as Well as Their Modulation After 6 Months Treatment With Oral Contraceptive.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01850095
• Other study ID #: 1622/11
• Status: Recruiting
• Phase: N/A
• First received: May 1, 2013
• Last updated: May 8, 2013
• Start date: March 2012
• Est. completion date: January 2015

Study information

• Verified date: May 2013
• Source: Federal University of São Paulo
• Contact: marco rocha, md
• Phone: 55-11-55799331
• Email: marcoderm[@]hotmail.com
• Is FDA regulated: No
• Health authority: Brazil: Ministry of HealthBrazil: National Committee of Ethics in ResearchBrazil: National Health Surveillance Agency
• Study type: Interventional

Clinical Trial Summary

Acne vulgaris is a chronic inflammatory disease that affects the pilosebaceous unit. Recent studies have demonstrated an increase number of acne cases in adult women. These cases are predominantly normoandrogenic and have some clinical differences when compared with the most common group, the adolescent. The local glandular metabolism converts some hormonal precursors to more active substances that increase the sebum production, leaving these areas more prone to increase the colonization to Propionibacterium Acnes (P. Acnes). Toll-like receptor 2, expressed by inflammatory cells play a crucial role in the innate immune response to this bacterium. Previous studies confirm that exist a reduced expression of CD1d by keratinocytes in acne lesion, what can be interpreted as a low antigen-present function. The influence of hormonal alteration in the sebaceous glands could modulate the expressions of TLR-2 and CD1d explaining the persistence of lesions in adult women. The change to more estrogenic metabolism, with use of specific contraceptive pills could normalize this immune-mediated inflammatory process.

Objective

To analyze how the peripheral androgen conversion can influence the toll-like receptor 2 and CD1d expression in women with inflammatory acne before and after 6 months of oral contraceptives with anti-androgen activity.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: January 2015
• Est. primary completion date: June 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 26 Years to 44 Years

Eligibility

Inclusion Criteria:

To all:

1. Signing the consent form before any study procedures;

2. women aged 26 to 44 years, not pregnant and in good health;

3. no topical treatment for acne in the past three months,

4. absence of the use of oral antibiotics in the last 3 months;

5. absence of the use of isotretinoin in the last 2 years;

6. absence of oral contraceptive use in the last 3 months;

7. absence of clinical evidence of immunosuppression and

8. accordance with the conditions of study, ability to understand and strictly follow the instructions given.

For the oral contraceptives group:

1. No contraindications to the use hormonal contraceptives.

For the azelaic acid group:

1. Absence of hypersensitivity to azelaic acid.

Exclusion Criteria:

For all

1. Women who do not agree with the conditions of the study or without the ability to understand and closely follow the guidelines received without availability to attend the revaluations or who refuse to sign the Informed Consent Form;

2. pregnant or lactating women;

3. use of the following oral medications: cortisone derivatives, lithium, anticonvulsants, isoniazid, oral contraceptives, androgens, danazol, iodides, bromides, disulfiram, cyclosporine, azathioprine, thiuram, vitamins B2, B6 and B12;

4. treatment of facial skin with topical retinoids (tretinoin and adapalene), azelaic acid, benzoyl peroxide, clindamycin, erythromycin, nicotinamina, alone or in combination, in the past 3 months;

5. treatment with oral antibiotics in the past 3 months;

6. acnogenics cosmetics.

For the group treated with oral contraceptives:

1. Presence of contraindications to oral contraceptive use:

1. Smokers over 35 years;

2. history of deep venous thrombosis;

3. history of stroke;

4. history of breast cancer;

5. presence of jaundice, and severe active liver disease or biliary disease;

6. diabetes mellitus for more than 20 years or eye injury, or neurological impairment;

7. blood pressure greater than or equal to 160 to 100 for systolic and diastolic;

8. cardiovascular disease and

9. presence of severe headache associated with blurred vision frequently.

For the group treated with azelaic acid:

1.Presense of allergic and / or irritating symptoms to the use of azelaic acid.

For the control group 1:

1. History, clinical signs and / or laboratory evidence of hyperandrogenism. 2 .Presence of inflammatory acne.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Acne
• Quality of Life

Intervention

Drug:
• treatment azelaic acid (azelan)
treatment for 6 months
• dorspirenone/ethynil estradiol

Locations

Country	Name	City	State
Brazil	Federal University of São Paulo-Dermatology	são Paulo

Sponsors (4)

Lead Sponsor	Collaborator
Marco Alexandre Dias da Rocha	Associacao Fundo de Incentivo a Psicofarmcologia, Bayer, Fleury

Country where clinical trial is conducted

Brazil, 

References & Publications (9)

Bhambri S, Del Rosso JQ, Bhambri A. Pathogenesis of acne vulgaris: recent advances. J Drugs Dermatol. 2009 Jul;8(7):615-8. — View Citation

Gollnick H, Cunliffe W, Berson D, Dreno B, Finlay A, Leyden JJ, Shalita AR, Thiboutot D; Global Alliance to Improve Outcomes in Acne. Management of acne: a report from a Global Alliance to Improve Outcomes in Acne. J Am Acad Dermatol. 2003 Jul;49(1 Suppl):S1-37. Review. — View Citation

Goulden V, Clark SM, Cunliffe WJ. Post-adolescent acne: a review of clinical features. Br J Dermatol. 1997 Jan;136(1):66-70. — View Citation

Goulden V, Stables GI, Cunliffe WJ. Prevalence of facial acne in adults. J Am Acad Dermatol. 1999 Oct;41(4):577-80. — View Citation

Kurokawa I, Danby FW, Ju Q, Wang X, Xiang LF, Xia L, Chen W, Nagy I, Picardo M, Suh DH, Ganceviciene R, Schagen S, Tsatsou F, Zouboulis CC. New developments in our understanding of acne pathogenesis and treatment. Exp Dermatol. 2009 Oct;18(10):821-32. doi: 10.1111/j.1600-0625.2009.00890.x. Epub 2009 Jun 23. Review. — View Citation

Poli F, Dreno B, Verschoore M. An epidemiological study of acne in female adults: results of a survey conducted in France. J Eur Acad Dermatol Venereol. 2001 Nov;15(6):541-5. — View Citation

Shen Y, Wang T, Zhou C, Wang X, Ding X, Tian S, Liu Y, Peng G, Xue S, Zhou J, Wang R, Meng X, Pei G, Bai Y, Liu Q, Li H, Zhang J. Prevalence of acne vulgaris in Chinese adolescents and adults: a community-based study of 17,345 subjects in six cities. Acta Derm Venereol. 2012 Jan;92(1):40-4. doi: 10.2340/00015555-1164. — View Citation

Thiboutot D. Acne: hormonal concepts and therapy. Clin Dermatol. 2004 Sep-Oct;22(5):419-28. Review. — View Citation

White GM. Recent findings in the epidemiologic evidence, classification, and subtypes of acne vulgaris. J Am Acad Dermatol. 1998 Aug;39(2 Pt 3):S34-7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Application of the questionnaire index of quality of life in Acne	AcneQol (Girman et al, 1996, Martin et al, 2001, Fehnel et al, 2003),	6 months	No
Other	Immunohistochemical analysis with quantitative digital blind:	For immunohistochemistry will be used the following markers: a polyclonal rabbit anti-TLR2 (ABBIOTEC 251,110) Biogen, Brazil.; mouse monoclonal anti-CD1d, clone NOR3.2 (Genway 20-272-1903). Biogen, Brazil.; Statistical comparisons are made between the following groups: control group 2 and the region with inflammatory lesions in the treatment group, region and region inflammatory non-inflammatory group of medications and treatment before inflammatory region before and after treatment.	6 months	No
Other	Serological blood measurements	Comparison of serological blood measurements of free and total testosterone, dihydroepiandrosterone sulfate (DHEAS), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and androsterone glucuronide, before and after the treatment.	6 months	No
Primary	Clinical evaluation of the treatment group	by the researcher: by counting the inflammatory lesions. by the research subjects: the general appearance of skin at the time of study entry and after the treatment. Will be used a 4-point scale: 0 = no acne, 1 = mild acne, moderate acne, and 2 = 4 = severe acne.	6 months	No
Secondary	Photographic study of the treatment group	This evaluation will be performed by two independent dermatologists, the degree of change in the intensity of acne, comparing the pre and post treatment photos through a 5-point scale: -2 = much worse, -1 = worse, 0 = unchanged; +1 = better, +2 = much better.	6 months	No