Spironolactone vs Doxycycline for Acne

(SD-ACNE Trial)

Recruiting at 14 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

350 Participants Needed

Trial Summary

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 data supports the effectiveness of the drug Doxycycline Hyclate for treating acne?

Research shows that Doxycycline Hyclate, when used in low doses, effectively reduces acne lesions. In a study, 11 out of 12 participants experienced a 50% reduction in acne lesions after eight weeks of treatment with Doxycycline Hyclate. ^{1 2 3 4 5}

Is doxycycline generally safe for treating acne?

Doxycycline is generally considered safe for treating acne, with fewer severe side effects compared to other similar antibiotics like minocycline. However, it can cause some side effects such as gastrointestinal issues, photosensitivity (increased sensitivity to sunlight), and in rare cases, more serious reactions. ^{1 2 6 7 8}

How does the drug Spironolactone vs Doxycycline for Acne differ from other acne treatments?

This treatment is unique because it combines spironolactone, which is typically used for hormonal acne due to its ability to block certain hormones, with doxycycline, an antibiotic that reduces inflammation and bacteria. This combination targets both hormonal and bacterial causes of acne, potentially offering a more comprehensive approach than using either drug alone. ^{1 2 3 6 9}

What is the purpose of this trial?

This trial compares two treatments for women with moderate to severe acne. One treatment helps balance hormones to reduce skin oiliness, while the other kills bacteria and reduces inflammation. The goal is to see which treatment is more effective and potentially reduce the need for long-term antibiotic use.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

References

1. Croatia pubmed.ncbi.nlm.nih.gov

The treatment of acne vulgaris with low dosage doxycycline. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Efficacy of minocycline compared with tetracycline in treatment of acne vulgaris. [2013]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Sarecycline: A Review of Preclinical and Clinical Evidence. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Effects of subantimicrobial-dose doxycycline in the treatment of moderate acne. [2022]

5. France pubmed.ncbi.nlm.nih.gov

A comparison of the efficacy and safety of lymecycline and minocycline in patients with moderately severe acne vulgaris. [2013]

6. France pubmed.ncbi.nlm.nih.gov

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

7. England pubmed.ncbi.nlm.nih.gov

The use and safety of doxycycline hyclate and other second-generation tetracyclines. [2022]

8. United States 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. [2018]

9. United States 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. [2013]