Comparative Effectiveness Study of Spironolactone Versus Doxycycline for Acne

• ClinicalTrials.gov Identifier: NCT04582383
• Recruitment Status: Recruiting
• First Posted: October 9, 2020
• Last Update Posted: October 25, 2022
• Sponsor: University of Pennsylvania
• Information provided by (Responsible Party): University of Pennsylvania

Study Description

Brief Summary:

Acne is common illness of adolescents and young adults which is associated with substantial morbidity. While topical treatments are often sufficient for mild acne, moderate to severe acne often requires treatment with systemic medications such as oral antibiotics, hormonal therapies such spironolactone, and isotretinoin. Sebum overproduction is fundamental to the pathogenesis of acne with associated disordered keratinization and subsequent microbial colonization and inflammation resulting in the clinical manifestations of acne. Given the influence of hormones on sebum production, therapies that address these underlying hormonal factors such as spironolactone and oral contraceptive pills represent an underutilized treatment option for women with acne and could help decrease the use of long-term oral antibiotics in this patient population. The purpose of this trial is to evaluate the comparative effectiveness of spironolactone versus doxycycline hyclate (tetracycline class antibiotic) for women with acne.

Condition or disease	Intervention/treatment	Phase
Acne	Drug: Spironolactone; Drug: Doxycycline Hyclate	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 400 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: 200 participants will be randomized to treatment with spironolactone 100mg/day and 200 participants will be randomized to treatment with doxycycline hyclate 100mg/day.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Multi-Center Comparative Effectiveness Study of Spironolactone Versus Doxycycline Hyclate for the Treatment of Acne in Women
• Actual Study Start Date: March 30, 2022
• Estimated Primary Completion Date: July 31, 2025
• Estimated Study Completion Date: July 31, 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: Spironolactone; In this arm, participants will receive spironolactone 100mg/day for the entirety of the study. To maximize the generalizability of the study, participants will be allowed to continue their current topical regimen as long as no changes were made in the 4 weeks prior to randomization. No additions to their topical regimen may be made during the study period.	Drug: Spironolactone; Dispensation of spironolactone according to the arm description.
Active Comparator: Doxycycline hyclate; This arm is an active-comparator arm in which participants will receive doxycycline hyclate 100mg/day for the entirety of the study. To maximize the generalizability of the study, participants will be allowed to continue their current topical regimen as long as no changes were made in the 4 weeks prior to randomization. No additions to their topical regimen may be made during the study period.	Drug: Doxycycline Hyclate; Dispensation of doxycycline hyclate according to the arm description.

Outcome Measures

Primary Outcome Measures :

1. Absolute change in inflammatory papules and pustules [ Time Frame: Baseline to Week 16 ]
   Difference in change in inflammatory papules and pustules between those randomized to spironolactone versus doxycycline hyclate

Secondary Outcome Measures :

1. Percentage achieving Investigator Global Assessment (IGA) Success (IGA grade of clear or almost clear; grade 0 or 1) [ Time Frame: Baseline to Week 8, and Week 16 ]
   Difference in percentage achieving IGA success between those randomized to spironolactone versus doxycycline hyclate
2. Change in comedonal lesions [ Time Frame: Baseline to Week 8, and Week 16 ]
   Difference in change in comedonal lesions between those randomized to spironolactone versus doxycycline hyclate
3. Change in Acne-QoL, an acne-specific quality of life measure [ Time Frame: Baseline to Week4, Week 8, Week 12, and Week 16 ]
   Difference in change in Acne-QoL score between those randomized to spironolactone versus doxycycline hyclate. There are 4 subscales: self perception, scored 0-30; role social, scored 0-24; role-emotional, scored 0-30; and acne symptoms, scored 0-30. Higher scores indicate better quality of life.
4. Change in Dermatology Life Quality Index (DLQI), a dermatology-specific quality of life measure [ Time Frame: Baseline to Week4, Week 8, Week 12, and Week 16 ]
   Difference in change in DLQI score between those randomized to spironolactone versus doxycycline hyclate. Scores range from 0-30, with lower scores indicated better quality of life.
5. Patient global assessment [ Time Frame: Baseline to Week4, Week 8, Week 12, and Week 16 ]
   Difference in change in patient global assessment scores between those randomized to spironolactone versus doxycycline hyclate.
6. Percentage on any topical medication at baseline who discontinued at least one of these topical medications (i.e. topical retinoid, benzoyl peroxide, and topical antibiotic) [ Time Frame: Baseline to Week 16 ]
   Difference between those randomized to spironolactone versus doxycycline hyclate

Eligibility Criteria

• Ages Eligible for Study: 16 Years to 40 Years (Child, Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Female sex assigned at birth
• Age 16-40 years old
• Acne defined as at least 10 inflammatory papules or pustules and an Investigator's Global Assessment (IGA) score of at least 2 as measured by the Comprehensive Acne Severity Scale
• Not currently pregnant or planning to become pregnant

Exclusion Criteria:

• Pregnancy
• Heart disease
• Renal disease
• Liver disease
• Orthostatic hypotension
• Addison's disease
• History of hyperkalemia
• Allergy to tetracycline-class antibiotic
• Allergy to spironolactone
• Concomitant use of medications known to interact with spironolactone or doxycycline or that may increase the risk for hyperkalemia, including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, eplerenone, nonsteroidal anti-inflammatory drugs, and digoxin.
• Treatment with spironolactone, an oral antibiotic, laser, photodynamic therapy, or chemical peel within the past 4 weeks
• Treatment with isotretinoin within the past 3 months
• Treatment with a drospirenone containing combined oral contraceptive
• Sebacia laser treatment within the past 12 months

Contacts and Locations

Contacts

Contact: David J Margolis, MD, PhD; 215-662-2590; margo@pennmedicine.upenn.edu

Contact: John S Barbieri, MD, MBA; 6172645932; jbarbieri@bwh.harvard.edu

Locations

United States, Arkansas

Johnson Dermatology; Recruiting

Fort Smith, Arkansas, United States, 72916

Contact: Sandra Johnson, MD

United States, California

University of California San Francisco; Recruiting

San Francisco, California, United States, 94115

Contact: Katrina Abuabara, MD

United States, Florida

University of Miami; Recruiting

Miami, Florida, United States, 33136

Contact: Jonette Keri, MD

New Horizon Research Center; Recruiting

Miami, Florida, United States, 33165

Contact: Lazaro Nunez, MD

United States, Indiana

Dawes Fretzin Clinical Research Group; Recruiting

Indianapolis, Indiana, United States, 46250

Contact: Scott Fretzin, MD

United States, Massachusetts

Brigham and Women's Hospital; Recruiting

Boston, Massachusetts, United States, 02115

Contact: John Barbieri, MD, MBA

United States, Ohio

Ohio State University Medical Center; Recruiting

Columbus, Ohio, United States, 43215

Contact: Benjamin Kaffenberger, MD

United States, Oregon

Oregon Health and Science University; Recruiting

Portland, Oregon, United States, 97239

Contact: Teri Greiling, MD, PhD

United States, Pennsylvania

Penn State University (Hershey Medical Center); Recruiting

Hershey, Pennsylvania, United States, 17033

Contact: Joslyn Kirby, MD

University of Pennsylvania; Recruiting

Philadelphia, Pennsylvania, United States, 45209

Contact: David Margolis, MD, PhD

Principal Investigator: David Margolis, MD, PhD

Sponsors and Collaborators

University of Pennsylvania

More Information

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT04582383
• Other Study ID Numbers: R34AR074733-01A1 ( U.S. NIH Grant/Contract )
• First Posted: October 9, 2020
• Last Update Posted: October 25, 2022
• Last Verified: October 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: IPD will be available to research teams within 1 year following study completion.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP)
• Time Frame: 1 year following study completion

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by University of Pennsylvania:

spironolactone; doxycycline

Additional relevant MeSH terms:

Acne Vulgaris; Acneiform Eruptions; Skin Diseases; Sebaceous Gland Diseases; Doxycycline; Spironolactone; 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