Comparative Effectiveness Study of Spironolactone Versus Doxycycline for Acne (SD-ACNE)

A Randomized, Double-Blind, Multi-Center Comparative Effectiveness Study of Spironolactone Versus Doxycycline Hyclate for the Treatment of Acne in Women

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Acne
• Intervention / Treatment: Drug: Spironolactone; Drug: Doxycycline Hyclate

• Study Type: Interventional
• Enrollment (Estimated): 350
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Fort Smith, Arkansas, United States, 72916
      • Johnson Dermatology
  • California
    • San Francisco, California, United States, 94115
      • University of California San Francisco
    • Sherman Oaks, California, United States, 92866
      • Cura Clinical Research
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
    • Miami, Florida, United States, 33165
      • New Horizon Research Center
  • Indiana
    • Indianapolis, Indiana, United States, 46250
      • Dawes Fretzin Clinical Research Group
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • New York
    • New York, New York, United States, 10016
      • New York University
    • North New Hyde Park, New York, United States, 11042
      • Northwell Health
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Dermatologists of Central States
    • Columbus, Ohio, United States, 43215
      • Ohio State University Medical Center
  • Oregon
    • Gresham, Oregon, United States, 97030
      • Cyn3rgy Research
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Philadelphia, Pennsylvania, United States, 45209
      • University of Pennsylvania
  • Texas
    • Arlington, Texas, United States, 76011
      • Arlington Research Center
    • Frisco, Texas, United States, 75034
      • North Texas Center for Clinical Research
    • Houston, Texas, United States, 77004
      • CCS Texas

Participation Criteria

Eligibility Criteria

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

Description

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
• Sebacia laser treatment within the past 12 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute change in inflammatory lesion count	Difference in change in inflammatory lesion count between those randomized to spironolactone versus doxycycline hyclate	Baseline to Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage achieving Investigator Global Assessment (IGA) Success (IGA grade of clear or almost clear; grade 0 or 1)	Difference in percentage achieving IGA success between those randomized to spironolactone versus doxycycline hyclate	Baseline to Week 8, and Week 16
Change in comedonal lesions	Difference in change in comedonal lesions between those randomized to spironolactone versus doxycycline hyclate	Baseline to Week 8, and Week 16
Change in Acne-QoL, an acne-specific quality of life measure	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.	Baseline to Week4, Week 8, Week 12, and Week 16
Change in Dermatology Life Quality Index (DLQI), a dermatology-specific quality of life measure	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.	Baseline to Week4, Week 8, Week 12, and Week 16
Patient global assessment	Difference in change in patient global assessment scores between those randomized to spironolactone versus doxycycline hyclate.	Baseline to Week4, Week 8, Week 12, and Week 16
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)	Difference between those randomized to spironolactone versus doxycycline hyclate	Baseline to Week 16

Collaborators and Investigators

• Sponsor: University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2022
• Primary Completion (Actual): February 14, 2026
• Study Completion (Estimated): July 31, 2027

Study Registration Dates

• First Submitted: September 30, 2020
• First Submitted That Met QC Criteria: October 7, 2020
• First Posted (Actual): October 9, 2020

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: spironolactone; doxycycline
• Additional Relevant MeSH Terms: Skin Diseases; Acneiform Eruptions; Sebaceous Gland Diseases; Skin and Connective Tissue Diseases; Acne Vulgaris; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Pregnanes; Steroids; Fused-Ring Compounds; Lactones; Naphthacenes; Pregnenes; Tetracyclines; Doxycycline; Spironolactone
• Other Study ID Numbers: R34AR074733-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD will be available to research teams within 1 year following study completion.
• IPD Sharing Time Frame: 1 year following study completion
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• 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