The Influence of Peripheral Androgen Conversion at Women Adult Acne

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by Federal University of São Paulo
Sponsor:
Collaborators:
Fleury
Associacao Fundo de Incentivo a Psicofarmcologia
Bayer
Information provided by (Responsible Party):
Marco Alexandre Dias da Rocha, Federal University of São Paulo
ClinicalTrials.gov Identifier:
NCT01850095
First received: May 1, 2013
Last updated: May 8, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention
Acne
Quality of Life
Drug: treatment azelaic acid (azelan)
Drug: dorspirenone/ethynil estradiol

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Diagnostic
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.

Resource links provided by NLM:


Further study details as provided by Federal University of São Paulo:

Primary Outcome Measures:
  • Clinical evaluation of the treatment group [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Photographic study of the treatment group [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Application of the questionnaire index of quality of life in Acne [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    AcneQol (Girman et al, 1996, Martin et al, 2001, Fehnel et al, 2003),

  • Immunohistochemical analysis with quantitative digital blind: [ Time Frame: 6 months ] [ Designated as safety issue: No ]

    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.


  • Serological blood measurements [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 60
Study Start Date: March 2012
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: treatment 1
topical acid azelaic, used 2 times a day for 6 months
Drug: treatment azelaic acid (azelan)
treatment for 6 months
Other Name: azelaic acid (azelan)
Active Comparator: treatment 2
contraceptive with drospirenone/ethinyl estradiol used for 6 months
Drug: dorspirenone/ethynil estradiol
Other Name: (yaz)
No Intervention: control
control group ( only take biopsies and blood samples )

  Eligibility

Ages Eligible for Study:   26 Years to 44 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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.

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  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01850095

Contacts
Contact: marco rocha, md 55-11-55799331 marcoderm@hotmail.com

Locations
Brazil
Federal University of São Paulo-Dermatology Recruiting
são Paulo, Brazil, 04038-001
Contact: marco rocha, md    55-11-55799331    marcoderm@hotmail.com   
Principal Investigator: marco rocha, md         
Sub-Investigator: edileia bagatin, Phd         
Sponsors and Collaborators
Marco Alexandre Dias da Rocha
Fleury
Associacao Fundo de Incentivo a Psicofarmcologia
Bayer
Investigators
Principal Investigator: marco rocha, md UNIFESP-EPM
  More Information

Publications:

Responsible Party: Marco Alexandre Dias da Rocha, MD, Federal University of São Paulo
ClinicalTrials.gov Identifier: NCT01850095     History of Changes
Other Study ID Numbers: 1622/11
Study First Received: May 1, 2013
Last Updated: May 8, 2013
Health Authority: Brazil: Ministry of Health
Brazil: National Committee of Ethics in Research
Brazil: National Health Surveillance Agency

Keywords provided by Federal University of São Paulo:
acne
adult
women
TLR
CD1d
androgens

Additional relevant MeSH terms:
Acne Vulgaris
Acneiform Eruptions
Skin Diseases
Facial Dermatoses
Sebaceous Gland Diseases
Androgens
Contraceptive Agents
Estradiol valerate
Estradiol 17 beta-cypionate
Estradiol 3-benzoate
Contraceptives, Oral
Estradiol
Polyestradiol phosphate
Azelaic acid
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Reproductive Control Agents
Therapeutic Uses
Contraceptive Agents, Female
Estrogens
Antineoplastic Agents
Dermatologic Agents

ClinicalTrials.gov processed this record on August 28, 2014