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Randomized Double-blind Study on the Benefit of Spironolactone for Treating Acne of Adult Woman. (FASCE)

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ClinicalTrials.gov Identifier: NCT03334682
Recruitment Status : Recruiting
First Posted : November 7, 2017
Last Update Posted : March 15, 2019
Sponsor:
Information provided by (Responsible Party):
Nantes University Hospital

Brief Summary:

Acne vulgaris of adult woman has increased over the past 10 years; it affects currently 20% to 30% of adult women.

The physiopathology of adult woman acne is distinguished from the teenager one by essentially 2 factors:

  • hormonal factor with a peripheral hyperandrogenism coupled with an hypersensibility of cutaneous androgens receptors of these women. But this point is still at the stage of hypothesis.
  • inflammatory factor linked with Propionibacterium Aces ; indeed these women received most of the time many cures of local and systematic antibiotics at the origin of resistant Propionibacterium Aces strains which lead to a chronical activation of cutaneous innate immunity.

On a therapeutic plan, four types of systemic treatment, approved in this indication are:

  • Tetracyclines which are problematic for the bacterial resistance and consequently constant relapse when they are stopped.
  • Zinc salts which target only the inflammatory lesions and were shown less effective than cycline
  • Antiandrogens, with acetate of cyproterone associated with risks of phlebitis and pulmonary embolism, and increase risk of triglycerides, cholesterol and hepatic balance.
  • The last alternative is represented by isotretinoin but the use in women of childbearing potential is binding because of the teratogen risks and the hyperandrogenism represents an identified risk of relapse.

In this context, the spironolactone could represent an interesting alternative. It blocks the 5-alpha-reductase receptors at sebaceous gland and inhibits Luteinizing hormone (LH) production at the pituitary level. It is not submitted to isotretinoin constraints, does not lead to bacterial resistance and targets the peripheral hyperandrogenism.

Currently, very few studies have been performed and on a weak number of patients but they showed that at low doses (lower than 200mg/day), spironolactone can be effective against acne.

In that context, it seemed clearly interesting to perform the first double-blind randomized study spironolactone vs cyclines which remains the moderate acne reference treatment and to demonstrate the superiority of spironolactone's efficacy in order to establish it as alternative way to cycline.


Condition or disease Intervention/treatment Phase
Acne Vulgaris Drug: spironolactone Drug: Doxycycline Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description: The products used in both arms will be over-encapsulated by the Pharmacy of Nantes University Hospital
Primary Purpose: Treatment
Official Title: Randomized Double-blind Study on the Benefit of Spironolactone for Treating Acne of Adult Woman.
Actual Study Start Date : January 31, 2018
Estimated Primary Completion Date : July 31, 2020
Estimated Study Completion Date : January 30, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Acne

Arm Intervention/treatment
Experimental: spironolactone
Spironolactone ARROW ® 75 mg, 150mg, orally, once a day during all the trial (12 months: 6 months on double-blinded spironolactone then 6 months on open-label spironolactone), + topical therapy during all the trial (benzoyl peroxide 5%)
Drug: spironolactone
Dispensation of spironolactone at each visit according to the arm description described above.

Active Comparator: doxycycline
(Doxycycline Sandoz 100 mg), 100mg/day during 3 months followed by placebo during 3 months, on double-blinded + topical therapy during all the trial (benzoyl peroxide 5%
Drug: Doxycycline
Dispensation of doxycycline then placebo, at each visit according to the arm description described above.




Primary Outcome Measures :
  1. Treatment efficacy [ Time Frame: Month 4 and Month 6 ]

    The treatment's efficacy will be determined by the rate of success in each arm. The best rate of success between Month 4 and Month 6 will be chosen for the final result. Rate of success, defined by a decrease of both Adult Female Acne Scoring Tool (AFAST) scores 1 and 2:

    1. AFAST score 1: decrease of at least 2 grades compared to baseline or to grade 0 if the baseline was at 1 and
    2. AFAST score 2: decrease to grade 1 if baseline was > 1 or to grade 0 if the baseline was at 1

    AFAST 1 (also called GEA) assesses the comedones (open and closed), the non-inflammatory lesions, the papules and pustules and the nodules. The stage is defined according to a global evaluation of severity of acne and ranges from Grade 0 (no acne) to Grade 5 (the worse situation).

    AFAST 2 assesses acne on an area from the left and right mandibular zone to the upper edge of the trunk and ranges from Grade 0 (no acne) to Grade 3 (the worse situation).



Secondary Outcome Measures :
  1. Clinical adverse events [ Time Frame: Within 12 months after randomization ]
    Number and type of Adverse Events (AE) and Serious Adverse Events (SAE) occurring from the beginning of the treatment until end of the follow-up

  2. Sodium abnormal values (biological adverse events) [ Time Frame: From 30 days to 7 days before randomization visit, Month 2, Month 4, Month 9 ]
    Sodium measurement (mmol/L)

  3. Potassium abnormal values (biological adverse events) [ Time Frame: From 30 days to 7 days before randomization visit, Month 2, Month 4, Month 9 ]
    potassium measurement (mmol/L)

  4. Chlore abnormal values (biological adverse events) [ Time Frame: From 30 days to 7 days before randomization visit, Month 2, Month 4, Month 9 ]
    Chlore measurement (mmol/L)

  5. Calcium abnormal values (biological adverse events) [ Time Frame: From 30 days to 7 days before randomization visit, Month 2, Month 4, Month 9 ]
    Calcium measurement (mmol/L)

  6. AFAST score 1 (GEA) at 0 or 1 [ Time Frame: Month 2, Month 4, Month 6, Month 9 and Month 12 ]
    Number of patients with AFAST score 1 (GEA) at 0 or 1.

  7. AFAST score 2 (Mandibular) at 0 or 1 [ Time Frame: Month 2, Month 4, Month 6, Month 9 and Month 12 ]
    Number of patients with AFAST score 2 (Mandibular) at 0 or 1.

  8. AFAST score 1 associated with AFAST score 2 at 0 or 1 [ Time Frame: M2, M4, M6, M9 and M12 ]
    Number of patients with both AFAST score 1 and AFAST score 2 at 0 or 1.

  9. Quality of life (cost-utility assessment and general quality of life assessment) [ Time Frame: Month 2, Month 4, Month 6, Month 9 and Month 12 ]
    EQ-5D (EuroQol 5 dimensions) questionnaire: The questionnaire focuses on five dimensions: mobility, personal autonomy, current activities, pain/discomfort, and anxiety/depression. For each of these dimensions, three answers are possible.

  10. Quality of life (specific to acne) [ Time Frame: Month 2, Month 4, Month 6, Month 9 and Month 12 ]
    Cardiff Acne disability Index (CADI) is a disease-specific questionnaire measuring disability induced by acne.

  11. Bacterial and parasital evaluations [ Time Frame: Day 0 (baseline) and Month 4 ]
    Presence of P acnes, M Furfur and S epidermidis, aureus

  12. Inflammatory lesions of the face [ Time Frame: Day 0 (baseline), Month 2, Month 4, Month 6, Month 9 and Month 12 ]
    Number of inflammatory lesions of the face

  13. retentional lesions of the face [ Time Frame: Day 0 (baseline), Month 2, Month 4, Month 6, Month 9 and Month 12 ]
    Number of retentional lesions of the face

  14. Face lesions [ Time Frame: Day 0 (baseline), Month 2, Month 4, Month 6, Month 9 and Month 12 ]
    Total number of face lesions

  15. Trunk lesions [ Time Frame: Day 0 (baseline), Month 2, Month 4, Month 6, Month 9 and Month 12 ]
    Factor F2 of ECLA scale ECLA ("Echelle de Cotation des Lésions d'Acné") is a scale for acne proposed by the dermatology research team of Nantes University Hospital. It is composed of 3 factors: Factor 1 (F1) counts the acne lesions on the face; Factor 2 (F2) counts the lesions acne on the trunk and Factor 3 (F3) counts the scars. In this study, the factor F2 will be used. The factor F2 assesses the extensive character of acne lesions on 5 defined areas: cervical areas (F2N); chest areas (F2C); back area (F2B) and arm area (F2A) according to a qualitative scale 0=absent, 1=poor 2=medium 3=significant. It is completed by the count of the present nodules in each area.

  16. Relapse [ Time Frame: Month 4 and Month 6 ]

    number of patients with relapse, defined as follows :

    1. AFAST score 1 (GEA score): increase of 2 points versus score of previous visit, in case of success Or
    2. AFAST score 2 (mandibular score): increase of 1 point versus score of previous visit, in case of success

  17. Reappearance of 10% and more of inflammatory lesions. [ Time Frame: Month 6 ]
    Number of patients with a reappearance of 10% and more of inflammatory lesions.

  18. Incremental cost-effectiveness ratio (cost per Quality-Adjusted Life-Year, QALY) of the comparison between the spironolactone and cycline. [ Time Frame: Month 6 ]
    costs: resources consumed, QALY: EQ-5D



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient with acne, with at least 10 inflammatory lesions and no more than 3 nodules
  • Patient who already had one cycline course for her acne treatment with a 3 months* wash out or who never had any cycline
  • Patient having signed an informed consent
  • Absence of use of oral antibiotics and Zinc salts in the last 30 days
  • Absence of use of systemic isotretinoin and antiandrogens in the last 6 months
  • Absence of microphysiotherapy in the last 15 da
  • Women of child-bearing age under contraception since 3 months (oral contraception, implant or IUD).
  • Patients with social security

Exclusion Criteria:

  • Patient affected by active /progressive diseases, as infections including Hidradenitis suppurativa, cancers, or endocrine syndrome (eg polycystic ovary syndrome), Addison's disease)
  • Patient affected by Rosacea
  • Patient with contra-indication to the use of one of the investigational products or auxiliary :

    • Patient with intolerance or hypersensitivity to cyclin's, spironolactone or to any ingredient present in associated benzoyl peroxide gel
    • Patient with significant impairment of renal excretory function, acute or chronic renal failure, anuria.
    • Patient with life-threatening or very severe hepatic impairment.(grade III or IV)
  • Patient with hyperkalaemia or strongly requiring potassium-sparing diuretics (eg amiloride, canrenoate, eplerenone, triamterene), or treated continuously with Angiotensin-converting-enzyme (ACE) inhibitors, angiotensin II antagonist, NSAIDs, heparin and molecular weight heparin, ciclosporin and tacrolimus.
  • Patient requiring topical isotretinoin or who stopped this drug since less than 2 weeks
  • Patient previously treated with spironolactone
  • Pregnant woman or likely to become pregnant or nursing and refusing to use an effective contraceptive method
  • Patient participating in another interventional clinical trial
  • Patient under guardianship or trusteeship

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03334682


Contacts
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Contact: Brigitte DRENO +33 240 08 31 18 brigitte.dreno@wanadoo.fr
Contact: Amir KHAMMARI +33 240 08 32 80 amir.khammari@chu-nantes.fr

Locations
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France
Chru Brest Not yet recruiting
Brest, France
Principal Investigator: Laurent MISERY         
CHU Caen Not yet recruiting
Caen, France
Contact: Anne Dompmartin, MD         
CHU Grenoble Not yet recruiting
Grenoble, France
Contact: Marie-Thérèse LECCIA         
CH La Rochelle Not yet recruiting
La Rochelle, France
Contact: Philippe Celerier, MD         
CH Le Mans Not yet recruiting
Le Mans, France
Contact: Nathalie BENETON         
CHU de Nantes - Dermatologie Recruiting
Nantes, France
Contact: Brigitte Dreno, PU PH         
Principal Investigator: Brigitte Dreno, PU PH         
CHU Poitiers Not yet recruiting
Poitiers, France
Contact: Ewa HAINAUT         
Cabinet du Dr Jean-Paul Claudel Not yet recruiting
Tours, France
Contact: Jean-Paul CLAUDEL         
CHRU Tours Not yet recruiting
Tours, France
Contact: Laurent Machet, MD         
Sponsors and Collaborators
Nantes University Hospital

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Responsible Party: Nantes University Hospital
ClinicalTrials.gov Identifier: NCT03334682     History of Changes
Other Study ID Numbers: RC16_0467
First Posted: November 7, 2017    Key Record Dates
Last Update Posted: March 15, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Acne Vulgaris
Acneiform Eruptions
Skin Diseases
Sebaceous Gland Diseases
Doxycycline
Spironolactone
Benzoyl Peroxide
Anti-Bacterial Agents
Anti-Infective Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Diuretics, Potassium Sparing
Diuretics
Natriuretic Agents
Dermatologic Agents