Spironolactone for Hyperandrogenism in Pubertal Girls

(CBS010 Trial)

Overseen By Melissa Gilrain, BS

Age: < 18

Sex: Female

Trial Phase: Phase < 1

Sponsor: University of Virginia

Must be taking: Spironolactone

Must not be taking: Eplerenone

Disqualifiers: Diabetes, Virilization, Cancer, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 2 weeks per treatment period

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests spironolactone to determine if it can help girls in mid- to late puberty with hyperandrogenism (high levels of male hormones) by regulating their hormone cycles, especially during sleep. The study aims to understand how this medication affects hormone release over time. Participants will receive either spironolactone or a placebo for a short period. Girls who have started puberty and experience symptoms like excess hair growth due to high testosterone levels might be suitable for this study. As an Early Phase 1 trial, this research focuses on understanding how spironolactone works in people, offering participants a chance to contribute to groundbreaking insights.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are taking medications that might interact with spironolactone, such as eplerenone, you may need to stop those. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that spironolactone is likely to be safe for humans?

Research shows that spironolactone is generally safe and well-tolerated. Studies have found that a daily dose of 25-100 mg is considered safe. This medication often treats hormone imbalance issues, such as excess male hormones in females. Although spironolactone is widely used and has a good safety record, all medications can have side effects. Common side effects include dizziness or changes in blood pressure. Always consult the study team or your doctor if you have any concerns. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Spironolactone is unique because it targets hyperandrogenism by blocking androgen receptors and reducing testosterone levels, which is different from standard treatments like oral contraceptives that mainly regulate hormone levels indirectly. Researchers are excited about spironolactone because it directly tackles the root cause of excess androgen, potentially offering a more targeted and effective approach. Additionally, spironolactone is already well-known for its safety profile in other conditions, which could make it a promising option for pubertal girls experiencing hyperandrogenism.

What evidence suggests that spironolactone might be an effective treatment for hyperandrogenism?

Studies have shown that spironolactone can lower male hormone levels in girls with excess hormones. One study demonstrated that taking spironolactone for 12 weeks reduced hormone production from the ovaries and adrenal glands. Another study found that spironolactone improved ovulation in girls with high male hormone levels. It also reduced skin oil, aiding acne caused by excess male hormones. In this trial, participants will receive either spironolactone or a placebo for 2 weeks as pretreatment. These findings suggest that spironolactone could help manage symptoms in girls with elevated male hormone levels. ^{4 6 7 8 9}

Who Is on the Research Team?

Christine M Burt Solorzano, MD

Principal Investigator

University of Virginia Center for Research in Reproduction

Are You a Good Fit for This Trial?

This trial is for mid to late pubertal girls aged 10-17 with hyperandrogenism, which could be high testosterone levels or excessive hair growth. They should be in good health overall and agree to avoid pregnancy using non-hormonal methods during the study.

Inclusion Criteria

I am committed to using non-hormonal birth control methods during the study.

I am a girl aged 10-17, either after my first period or in the later stages of puberty.

You have high levels of testosterone in your blood or show signs of excessive hair growth.

Exclusion Criteria

Your total testosterone level is higher than 150 ng/dl.

I have symptoms or a diagnosis of low testosterone due to pituitary or hypothalamic causes.

You are pregnant or currently breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are pretreated with spironolactone or placebo for 2 weeks before each clinical research unit admission

2 weeks per treatment period

2 admissions (in-person)

Crossover

Participants switch treatments between spironolactone and placebo for another 2 weeks before the second admission

2 weeks per treatment period

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Spironolactone

Trial Overview The trial tests if Spironolactone, a medication that blocks androgen receptors, can normalize sleep-wake luteinizing hormone pulse frequency in these girls. The study also looks at its effects on other hormones like LH and FSH compared to a placebo.

How Is the Trial Designed?

Group I: Spironolactone Experimental Treatment 1 Intervention

Prior to the first or second admission (randomly determined), participants will be pretreated for 2 weeks with spironolactone (50 mg twice daily).

Group II: Placebo Placebo Group 1 Intervention

Prior to the first or the second admission (randomly determined), participants will be pretreated for 2 weeks with placebo (twice daily).

Spironolactone is already approved in United States, European Union for the following indications:

Approved in United States as Aldactone for:

• High blood pressure
• Heart failure
• Liver scarring
• Kidney disease
• Low blood potassium
• Early puberty in boys
• Acne
• Excessive hair growth in women

Approved in European Union as Aldactone for:

• Fluid retention due to heart failure
• Liver scarring
• Kidney disease
• High blood pressure
• Low blood potassium

Who Is Running the Clinical Trial?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Published Research Related to This Trial

The combination of spironolactone and testolactone effectively manages familial male precocious puberty by maintaining plasma testosterone levels while blocking its receptor, as shown in an 18-month pilot study followed by an extended treatment of 2 to 4.2 years in eight boys.

As boys continued treatment, they experienced a rise in gonadotropin levels, leading to a diminished response to the therapy; however, adding the LHRH agonist deslorelin successfully reduced peak LH, plasma testosterone, and bone maturation rate, helping to regain control over puberty.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of familial male precocious puberty with spironolactone, testolactone, and deslorelin. Laue, L., Jones, J., Barnes, KM., et al.[2018]

In a study of nine boys aged 3.3 to 7.7 years with familial male precocious puberty, a combination of the antiandrogen spironolactone and the estrogen synthesis inhibitor testolactone effectively normalized growth rates and bone maturation after at least six months of treatment.

The combined therapy also helped control symptoms like acne and aggressive behavior without significant adverse effects, although further research is needed to evaluate long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of familial male precocious puberty with spironolactone and testolactone. Laue, L., Kenigsberg, D., Pescovitz, OH., et al.[2013]

In a study of 13 women with anovulatory oligomenorrhea and hyperandrogenism, treatment with spironolactone led to ovulation in 85% of participants and significant reductions in hormone levels such as LH and testosterone over six menstrual cycles.

Spironolactone also improved symptoms of hirsutism in 70% of the women and restored regular menstrual cycles in 85%, with only mild side effects reported, indicating its efficacy and safety as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction of ovulation with spironolactone (Aldactone) in anovulatory oligomenorrheic and hyperandrogenic women. Evron, S., Shapiro, G., Diamant, YZ.[2019]

In a study of 34 hirsute adolescents treated with spironolactone for 8 months, 70.6% showed significant improvement in hirsutism, indicating its efficacy as a treatment.

All participants experienced a decrease in testosterone levels, suggesting that spironolactone effectively reduces androgen levels, which is likely a key mechanism in alleviating hirsutism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The treatment of hirsutism in adolescent girls with spironolactone]. Malinova, M.[2013]

A review of five studies indicates that spironolactone may be an effective treatment for hirsutism in women with polycystic ovary syndrome (PCOS), showing a positive trend in outcomes.

The research highlights that while various treatment options exist for hirsutism, spironolactone has demonstrated promising results in addressing this common issue associated with PCOS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spironolactone for hirsutism in polycystic ovary syndrome. Christy, NA., Franks, AS., Cross, LB.[2013]

Spironolactone, at a dose of 5 mg/kg daily for one week, significantly increased serum LH levels by 60% in boys with delayed puberty, indicating its potential efficacy in stimulating gonadotropin secretion.

The drug's mechanism involves blocking testosterone synthesis and competing for androgen receptors, but individual responses varied, especially in patients with Kallmann's syndrome, highlighting the need for larger doses to achieve consistent results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spironolactone stimulation of gonadotropin secretion in boys with delayed adolescence. Santen, RJ., Kulin, HE., Loriaux, DL., et al.[2018]

In a study of 63 women with hyperandrogenic skin disorders due to polycystic ovary syndrome (PCOS), spironolactone was found to be an effective and safe treatment, with significant improvement reported after an average of 25.7 months of therapy.

The effects of spironolactone were long-lasting, with 38 patients maintaining improvement for an average of 33.7 months after stopping the medication, although some experienced relapse within 17.5 months, particularly those with the ovulatory PCOS phenotype.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Lasting Effects of Spironolactone after its Withdrawal in Patients with Hyperandrogenic Skin Disorders. Sabbadin, C., Beggiao, F., Keiko Vedolin, C., et al.[2023]

In a study of 100 children, spironolactone was commonly used in diuretic regimens, particularly for those with heart disease and chronic lung disease, with an average treatment duration of 16 days.

While initial use of spironolactone was associated with hyperkalemia (high potassium levels), long-term use led to hypokalemia (low potassium levels), highlighting the need for careful potassium monitoring in pediatric patients, especially those on multiple diuretics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with spironolactone in pediatrics. Buck, ML.[2013]

In a study of 82 young women with polycystic ovary syndrome (PCOS), both spironolactone and metformin improved menstrual cycle frequency and reduced hirsutism, but spironolactone was more effective in these areas.

Spironolactone was associated with fewer adverse events compared to metformin, making it a safer option for managing symptoms of PCOS, while both medications improved insulin sensitivity and hormonal levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of efficacy of spironolactone with metformin in the management of polycystic ovary syndrome: an open-labeled study. Ganie, MA., Khurana, ML., Eunice, M., et al.[2013]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04075149

Does Treatment of Androgen Excess Using Spironolactone ... This is a non-randomized, clinical pilot study testing whether 16 weeks of spironolactone improves ovulation rates in post-menarcheal girls with androgen excess ...

2. allclinicaltrials.com allclinicaltrials.com/study/NCT01422759

Effect of Spironolactone on Adrenal or Ovarian Androgen ... Whether 12 weeks of spironolactone can reduce androgen production from ovaries and adrenal glands of girls with obesity and androgen excess.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8826298/

Female Adult Acne and Androgen Excess The most used antiandrogen, spironolactone, has been shown to decrease sebum production [128]. Small placebo-controlled prospective studies have shown ...

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT01422759/effect-of-spironolactone-on-adrenal-or-ovarian-androgen-production-in-overweight-pubertal-girls-with-androgen-excess

Effect of Spironolactone on Adrenal or Ovarian Androgen ... This study will test whether spironolactone administration can ameliorate androgen (male hormone) overproduction in overweight pubertal girls ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0889854521005027

HYPERANDROGENISM IN THE ADOLESCENT SUMMARY. Problems of hyperandrogenism are becoming increasingly recognized in the female adolescent. Manifestations of androgen excess can have both farreaching ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01422759?term=AREA%5BConditionSearch%5D(%22Hyperandrogenism%22)%20AND%20AREA%5BInterventionSearch%5D(%22mineralocorticoid%20receptor%20antagonists%22)&rank=6

Effect of Spironolactone on Adrenal or Ovarian Androgen ... Also called a data safety and monitoring board, or DSMB. Early Phase 1 (formerly listed as Phase 0). A phase of research used to describe exploratory trials ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10010138/

The Efficacy and Safety of Oral and Topical Spironolactone ... Spironolactone is an effective and safe treatment of androgenic alopecia which can enhance the efficacy when combined with other conventional treatments such ...

8. clinicaltrial.be clinicaltrial.be/en/details/75577?per_page=100&recruiting=1&enrolling_by_invitation=0&active_not_recruiting=0&not_yet_recruiting=0&completed=0&only_recruiting=1&only_eligible=0

Effect of Spironolactone on Adrenal or Ovarian Androgen P... This study will test whether spironolactone administration can ameliorate androgen (male hormone) overproduction in overweight pubertal ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10424142/

Efficacy and safety of anti-androgens in the management ... ... Androgen Excess & PCOS Society criteria, and using a form of contraception. ... data suggests that 25–100 mg daily of spironolactone appears to be safe.