Spironolactone vs Doxycycline for Acne

(SD-ACNE Trial)

Not currently recruiting at 19 trial locations

Overseen By David J Margolis, MD, PhD

Age: < 65

Sex: Female

Trial Phase: Phase 4

Sponsor: University of Pennsylvania

Must not be taking: Ace inhibitors, Arbs, Nsaids, Digoxin

Disqualifiers: Pregnancy, Heart disease, Renal disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two treatments for acne: spironolactone, a hormone-based therapy, and doxycycline, an antibiotic. The goal is to determine which treatment is more effective for women with acne beyond occasional spots, specifically those with at least 10 noticeable pimples or pustules. Participants may continue using their usual skin treatments if they have not changed them recently. The trial seeks women who are not pregnant or planning to become pregnant and do not have certain health issues, such as heart or kidney disease. As a Phase 4 trial, the treatments are already FDA-approved and proven effective, aiming to understand how they benefit more patients.

Will I have to stop taking my current medications?

You may need to stop taking certain medications that interact with spironolactone or doxycycline, such as some blood pressure medications and anti-inflammatory drugs. If you're currently using spironolactone, oral antibiotics, or certain acne treatments, you might need to stop them for a specific period before joining the trial.

What is the safety track record for these treatments?

Research has shown that spironolactone is generally well-tolerated for treating acne, with many women using it without major issues. However, side effects are common. Some people may need to urinate more often; one study found this occurred in about 29% of users. There is also a small risk of developing high potassium levels, though this is rare, especially in women under 45.

Doxycycline, a commonly used antibiotic for acne and other infections, can cause side effects. In one study, 40.2% of users reported issues such as stomach upset or increased sensitivity to sunlight. It is important to note that doxycycline can harm an unborn baby, making it unsafe during pregnancy.

Both treatments have been used for a long time, and their side effects are well-known, making them relatively safe options for many people considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about spironolactone for acne because it offers a hormone-targeting approach, unlike the standard antibiotics or topical treatments. Spironolactone works by blocking androgen receptors, which can reduce oil production in the skin, a major factor in acne development. This makes it particularly promising for individuals with hormonal acne, offering an alternative for those who may not respond well to traditional treatments like doxycycline.

What evidence suggests that this trial's treatments could be effective for acne?

This trial will compare the effectiveness of spironolactone and doxycycline hyclate for treating acne. Research has shown that spironolactone can help treat acne in women. In one study, 19% of women saw improvement after 12 weeks, compared to just 6% who took a placebo (a pill with no active medicine). Another study found that spironolactone worked even better after 24 weeks than after 12 weeks by addressing hormonal causes of acne.

Participants in another arm of this trial will receive doxycycline hyclate, which effectively reduces red, swollen acne spots. In a study, 33% of people had a good or excellent response. Doxycycline has been safely used for acne for a long time, making it a dependable choice for many. These treatments work differently: spironolactone targets hormones, while doxycycline is an antibiotic. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for women aged 16-40 with moderate to severe acne, not pregnant or planning pregnancy. Participants must have at least 10 inflamed pimples and a certain severity score on an acne scale. Excluded are those with allergies to tetracycline antibiotics, heart/liver/renal disease, history of high potassium levels, recent use of specific acne treatments or drugs that interact with the trial medications.

Inclusion Criteria

Not currently pregnant or planning to become pregnant

I was assigned female at birth.

I am between 16 and 40 years old.

Exclusion Criteria

I have kidney disease.

I have had Sebacia laser treatment in the last year.

I am not taking medications that could react badly with spironolactone or doxycycline.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either spironolactone or doxycycline hyclate 100mg/day for the entirety of the study

16 weeks

Visits at baseline, Week 4, Week 8, Week 12, and Week 16

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Doxycycline Hyclate
• Spironolactone

Trial Overview

The study compares Spironolactone (a hormonal therapy) against Doxycycline Hyclate (an antibiotic) in treating women's acne. It aims to see which treatment is more effective while potentially reducing long-term antibiotic use by addressing hormonal factors influencing sebum production.

How Is the Trial Designed?

Group I: Spironolactone Experimental Treatment 1 Intervention

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.

Group II: Doxycycline hyclate Active Control 1 Intervention

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.

Doxycycline Hyclate is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Doxycycline Hyclate for:

• Acne
• Malaria
• Skin infections
• Sexually transmitted infections
• Lyme disease

Approved in European Union as Doxycycline Hyclate for:

• Acne
• Malaria
• Skin infections
• Sexually transmitted infections
• Lyme disease

Approved in Canada as Doxycycline Hyclate for:

• Acne
• Malaria
• Skin infections
• Sexually transmitted infections
• Lyme disease

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Published Research Related to This Trial

In a 16-week study involving 12 participants with inflammatory acne, a maintenance dose of 20 mg of doxycycline hyclate taken twice daily was effective in maintaining improvement after an initial treatment phase.

After the first eight weeks of treatment with 100 mg daily, 11 out of 12 subjects showed a 50% reduction in acne lesions, and those who continued with the lower dose of doxycycline maintained their improvement, while the placebo group did not.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The treatment of acne vulgaris with low dosage doxycycline. Parish, LC., Parish, JL., Routh, HB., et al.[2022]

Doxycycline hyclate (DH) has a favorable safety profile, especially in its delayed-release form (Doryx), compared to the standard powder form (Vibramycin), making it a safer option for treating conditions like acne and rosacea.

Despite historical safety concerns associated with tetracyclines, including gastrointestinal issues and effects on tooth development, subantimicrobial dosing of DH has shown to be effective and safe for acne treatment, supporting its continued use in dermatology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use and safety of doxycycline hyclate and other second-generation tetracyclines. Sloan, B., Scheinfeld, N.[2022]

In a study involving 51 adults with moderate acne, treatment with subantimicrobial-dose doxycycline significantly reduced the number of acne lesions compared to placebo, demonstrating its efficacy in improving clinical outcomes.

The treatment was well tolerated and did not alter skin flora or increase antibiotic resistance, indicating it is a safe option for managing moderate acne without the risk of promoting resistant bacteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of subantimicrobial-dose doxycycline in the treatment of moderate acne. Skidmore, R., Kovach, R., Walker, C., et al.[2022]

In a study involving 144 patients with moderately severe acne, lymecycline and minocycline were found to be equally effective in reducing both inflammatory and non-inflammatory acne lesions, with lymecycline reducing inflammatory lesions by 50.6% and minocycline by 52.2%.

Both treatments were well tolerated, with only 4.3% of lymecycline and 4.1% of minocycline recipients experiencing mild treatment-related adverse events, and lymecycline showed slightly fewer gastrointestinal and dermatological side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of the efficacy and safety of lymecycline and minocycline in patients with moderately severe acne vulgaris. Grosshans, E., Belaïch, S., Meynadier, J., et al.[2013]

In a study of 49 patients with moderate acne, minocycline showed a faster time to achieve noninflammatory acne status compared to tetracycline, with twice as many patients reaching this status after six weeks.

Both treatments had similar side effects, and no significant abnormalities were found in blood tests, indicating that minocycline is a safe and effective option for treating acne.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of minocycline compared with tetracycline in treatment of acne vulgaris. Hubbell, CG., Hobbs, ER., Rist, T., et al.[2013]

Sarecycline is a newly approved oral antibiotic specifically designed for treating moderate to severe acne vulgaris in patients aged 9 and older, marking the first novel systemic antibiotic for acne in decades.

It has a narrower antibacterial spectrum, primarily targeting C. acnes and some Gram-positive bacteria, which may lead to fewer side effects and a lower risk of developing antibiotic resistance compared to broader-spectrum tetracyclines like minocycline and doxycycline.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sarecycline: A Review of Preclinical and Clinical Evidence. Moore, AY., Del Rosso, J., Johnson, JL., et al.[2023]

A review by the French National Pharmacovigilance Committee found that minocycline was associated with more frequent and severe adverse effects compared to doxycycline during tetracycline therapy.

Minocycline was linked to a higher incidence of life-threatening hypersensitivity reactions and autoimmune effects, indicating a less favorable risk-benefit balance, especially for treating acne.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fewer adverse effects with doxycycline than with minocycline. [2013]

In a phase 2 study involving 285 patients aged 12 to 45, sarecycline at doses of 1.5 mg/kg and 3.0 mg/kg significantly reduced inflammatory acne lesions compared to placebo, demonstrating its efficacy as a treatment for moderate to severe acne.

Sarecycline was found to be safe and well tolerated, with low rates of adverse events, including gastrointestinal issues, and no serious adverse events reported, suggesting it has a favorable safety profile compared to other antibiotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Sarecycline, a Novel, Once-Daily, Narrow Spectrum Antibiotic for the Treatment of Moderate to Severe Facial Acne Vulgaris: Results of a Phase 2, Dose-Ranging Study. Leyden, JJ., Sniukiene, V., Berk, DR., et al.[2018]

Doxycycline calcium demonstrated a dose-response effect in treating moderate to severe inflammatory acne, with the highest dose (2.4 mg/kg/day) showing significant improvement compared to placebo over a 12-week period.

The study confirmed that higher doses not only improved acne symptoms but also had a measurable incidence of gastrointestinal side effects, indicating a need for careful dose management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, phase 2, dose-ranging study in the treatment of moderate to severe inflammatory facial acne vulgaris with doxycycline calcium. Leyden, JJ., Bruce, S., Lee, CS., et al.[2013]

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