U01AR079752

A Randomized, Double-Blind, Multi-Center Comparative Effectiveness Study of Spironolactone versus Doxycycline Hyclate for the Treatment of Acne in Women - Project Summary/Abstract

Acne is one of the most common diseases worldwide, affecting 85% of adolescents and often persisting into adulthood. Acne is responsible for a greater global burden of disease than psoriasis, cellulitis, and melanoma. Although mild acne can usually be managed with topical medications, moderate to severe acne often requires treatment with systemic medications such as oral antibiotics, spironolactone, and isotretinoin.

While these medications are a standard part of care, there are very few randomized clinical trials showing efficacy and none that show comparative effectiveness between these commonly used treatment options. The Institute of Medicine has identified this area as one of the top priorities for comparative effectiveness research. In addition, little is known about the effects of these different treatments on the microbiome.

Previous work by our group has shown oral antibiotics are the most common systemic medication used in the treatment of acne, and patients frequently use them for more than one year. In fact, dermatologists prescribe more antibiotics per capita than any other specialty. However, prolonged antibiotic use may be associated with a variety of adverse outcomes including bacterial antibiotic resistance, pharyngitis, collagen vascular illnesses, inflammatory bowel disease, and breast and colon cancer.

As a result, there is growing international interest and attention, specifically from the Centers for Disease Control, regarding improving antibiotic stewardship in the outpatient setting. Multiple clinical guidelines for acne have recommended reducing the use of antibiotics through the use of non-antimicrobial therapies and by limiting the duration of therapy.

For women with moderate to severe acne, spironolactone may represent an effective, well-tolerated therapeutic alternative to oral antibiotics. Originally developed as a potassium-sparing diuretic, for many years it has also been used off-label for acne due to its potential impact on hormonal pathogenesis of this disease. However, despite expert opinion supporting the use of spironolactone in the treatment of acne, its use remains relatively uncommon, and clinical evidence demonstrating the effectiveness of spironolactone is limited to small, often retrospective studies. Trials comparing the effectiveness of spironolactone to that of other medications such as oral antibiotics are lacking.

In Specific Aim 1, we will conduct a double-blind randomized controlled non-inferiority comparative effectiveness study of spironolactone versus doxycycline for women with acne. Since oral tetracycline-class antibiotics like doxycycline are currently the most common systemic medication prescribed for acne, the results of this trial will have substantial implications for the treatment of acne.

In Specific Aim 2, we will evaluate the impact of spironolactone versus doxycycline treatment on the microbiome, which will provide valuable insights regarding the relative effects of antibiotic (doxycycline) versus non-antibiotic (spironolactone) acne treatments on the microbiome.

This trial will significantly influence healthcare practice with respect to the treatment of moderate to severe acne in women and inform policy regarding more appropriate use of antibiotics throughout medicine.

Trustees Of The University Of Pennsylvania

THE NATIONAL INSTITUTE OF AND MUSCULOSKELETAL AND SKIN DISEASES (NIAMS) MISSION IS TO SUPPORT RESEARCH INTO THE CAUSES, TREATMENT, AND PREVENTION OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES, TRAINING OF BASIC AND CLINICAL SCIENTISTS TO CARRY OUT THIS RESEARCH, AND DISSEMINATION OF INFORMATION ON RESEARCH PROGRESS IN THESE DISEASES. THE EXTRAMURAL PROGRAM PROMOTES AND SUPPORTS BASIC, TRANSLATIONAL, AND CLINICAL STUDIES OF SYSTEMIC RHEUMATIC AND AUTOIMMUNE DISEASES, SKIN BIOLOGY AND DISEASES, BONE BIOLOGY AND DISEASES, MUSCLE BIOLOGY AND DISEASES, AND JOINT BIOLOGY AND DISEASES AND ORTHOPAEDICS. NIAMS SYSTEMIC RHEUMATIC AND AUTOIMMUNE DISEASES PROGRAMS ADDRESS BASIC, TRANSLATIONAL, AND CLINICAL RESEARCH, INCLUDING CLINICAL TRIALS AND OBSERVATIONAL AND MECHANISTIC STUDIES, FOCUSED ON IMMUNE-MEDIATED ARTHRITIS AND AUTOIMMUNE-RELATED ACUTE AND CHRONIC DISORDERS IN ADULTS AND CHILDREN. NIAMS SKIN BIOLOGY AND DISEASES PROGRAMS SUPPORT BASIC, TRANSLATIONAL, AND CLINICAL RESEARCH IN SKIN, INCLUDING BOTH COMMON AND RARE SKIN DISEASES. THESE PROGRAMS INCLUDE INVESTIGATIONS OF THE BASIC MOLECULAR, CELLULAR, AND DEVELOPMENTAL BIOLOGY OF SKIN, AS WELL AS STUDIES OF SKIN AS AN IMMUNE, SENSORY, ENDOCRINE, AND METABOLIC ORGAN. NIAMS BONE BIOLOGY AND DISEASES PROGRAMS SUPPORT RESEARCH ON THE CONTROL OF BONE FORMATION, RESORPTION, AND MINERALIZATION AS WELL AS THE EFFECTS OF SIGNALING MOLECULES ON BONE CELLS. THEY SUPPORT CLINICAL STUDIES OF INTERVENTIONS TO PREVENT FRACTURES ASSOCIATED WITH OSTEOPOROSIS AND RESEARCH INTO LESS COMMON BONE DISEASES. NIAMS MUSCLE BIOLOGY AND DISEASES PROGRAMS ENCOURAGE RESEARCH ON MUSCLE DEVELOPMENTAL BIOLOGY, GROWTH, MAINTENANCE, AND HYPERTROPHY, PHYSIOLOGY OF CONTRACTION, STRUCTURAL BIOLOGY OF THE CONTRACTILE APPARATUS, DISEASE MECHANISMS, BIOMARKERS AND OUTCOME MEASURES, AND DEVELOPMENT AND CLINICAL TESTING OF THERAPIES FOR CONDITIONS INCLUDING THE MUSCULAR DYSTROPHIES. NIAMS JOINT BIOLOGY, DISEASES, AND ORTHOPAEDICS PROGRAMS SUPPORT A BROAD SPECTRUM OF RESEARCH CENTERED ON THE INTERPLAY AMONG THE BODY'S MUSCLES, BONES, AND CONNECTIVE TISSUES. THEY ENCOURAGE TISSUE ENGINEERING AND REGENERATIVE MEDICINE RESEARCH, MOLECULAR BIOLOGY, IMAGING, AND CLINICAL RESEARCH, AND THE TREATMENT AND PREVENTION OF ORTHOPAEDIC CONDITIONS. NIAMS PARTICIPATES IN THE SMALL BUSINESS INNOVATION RESEARCH (SBIR) AND SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAMS. THE SBIR PROGRAM IS INTENDED TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE STTR PROGRAM IS INTENDED TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.846 - Arthritis, Musculoskeletal and Skin Diseases Research

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [HHS - NIH]

Philadelphia, Pennsylvania 191044865 United States

Single Zip Code

NIAMS Clinical Trial Implementation Cooperative Agreement (U01 Clinical Trial Required) (PAR-18-594)

Amendment Since initial award the End Date has been extended from 07/31/26 to 07/31/27 and the total obligations have increased 249% from $1,040,468 to $3,635,308.