Recruiting

Early Phase 1

SpironolactoneDoes Spironolactone Normalize Sleep-wake Luteinizing Hormone Pulse Frequency in Pubertal Girls With Hyperandrogenism?

Sponsor:

University of Virginia

Code:

NCT04723862

Conditions

Hyperandrogenism

Polycystic Ovary Syndrome

Puberty

Eligibility Criteria

Sex: Female

Age: 10 - 17

Healthy Volunteers: Accepted

Interventions

Spironolactone

Placebo

Study Details

Brief summary:

The purpose of this study is to determine if, in mid- to late pubertal girls with hyperandrogenism (HA), androgen-receptor blockade (spironolactone) alone normalizes sleep-wake luteinizing hormone (LH) pulse frequency (primary endpoint) and overall LH and follicle-stimulating hormone secretion (secondary endpoints).

Conditions

Hyperandrogenism

Polycystic Ovary Syndrome

Puberty

Study ID

NCT04723862

Start date

Nov 12, 2021

Status verified date

Jul, 2025

Completion date

Dec 1, 2025

Anticipated

Primary completion date

Oct 1, 2025

Anticipated

Eligibility Criteria

Sex: Female

Age: 10 - 17

Healthy Volunteers: Accepted

Inclusion Criteria:

Mid- to late pubertal adolescent girls as signified by either (a) post-menarcheal status (Tanner breast stages 2-5) or (b) Tanner breast stage of 4 or 5 (whether pre-menarcheal or post-menarcheal) ages 10-17 years.
Hyperandrogenism, defined as a serum (calculated) free testosterone concentration greater than the Tanner stage-specific reference range and/or clinical hirsutism
General good health (excepting obesity, hyperandrogenism, PCOS, and adequately-treated hypothyroidism)
Willing to strictly avoid pregnancy with use of reliable non-hormonal methods during the study period.

Exclusion Criteria:

Inability/incapacity to provide informed consent
Males will be excluded (hyperandrogenism is unique to females)
Age < 10 or > 17 years (this study is designed to elucidate mechanisms underlying emerging PCOS in mid- to late pubertal adolescent girls
Post-menarcheal by > 4 years
Obesity resulting from a well-defined endocrinopathy, or genetic syndrome
To ensure that blood withdrawal is within safe limits, weight < 21.5 kg is an exclusion criterion.
Since underweight can alter pulsatile LH secretion, BMI-for-age percentile < 5 is an exclusion criterion.
Positive pregnancy test or current lactation. Subjects with a positive pregnancy test will be informed of the result by the screening physician. Under Virginia law, parental notification is not required for minors. However, the screening physician will encourage the subject to tell her parent(s). We will counsel the adolescent about the importance of appropriate prenatal care/counseling. We will offer appropriate follow-up at the Teen Health Clinic at UVA and/or encourage the adolescent to secure prompt care via their primary care physician's office.
Evidence for non-physiologic or non-PCOS causes of hyperandrogenism and/or anovulation
Evidence of virilization (e.g., rapidly progressive hirsutism, deepening of the voice, clitoromegaly)
Total testosterone > 150 ng/dl, which suggests the possibility of virilizing ovarian or adrenal tumor.
DHEA-S elevation > 1.5 times the upper reference range limit. Mild elevations may be seen in adolescent HA and in PCOS, and will be accepted in these groups.
Early morning 17-hydroxyprogesterone > 300 ng/dl measured in the follicular phase, which suggests the possibility of congenital adrenal hyperplasia (if elevated during the luteal phase, the 17-hydroxyprogesterone will be repeated during the follicular phase). NOTE: if a 17-hydorxyprogesterone > 300 ng/dl is confirmed on repeat testing, an ACTH stimulated 17-hydroxyprogesterone < 1000 ng/dl performed by the subject's personal physician will be required for study participation.
Any abnormal TSH concentration will trigger repeat testing. In many cases when TSH is initially abnormal, a repeat TSH will be normal. These subjects will be permitted to continue study. If TSH remains abnormal on repeat testing, the subject will be referred to her primary medical provider. In some cases, a participant's primary medical provider will elect to simply observe a mildly low (> 0.1) or mildly elevated (< 10) if stable. In such cases, we will accept a TSH between 0.3 and 7 (inclusive) if it has remained stable for at least 6 months-such TSH values are exceedingly unlikely to influence the central reproductive axis or to influence the risks of the study. Notably, subjects with reasonably-treated primary hypothyroidism-reflected by TSH values between 0.3 and 7-on a stable dose of thyroid hormone (i.e., same dose for at least 2 months) will not be excluded.
Prolactin concentration > 30 ng/mL (confirmed on repeat). Mild prolactin elevations may be seen in adolescents and women with HA/PCOS or obesity.
History and/or physical exam findings suggestive of Cushing's syndrome, adrenal insufficiency, or acromegaly.
History and/or physical exam findings suggestive of hypogonadotropic hypogonadism (e.g., symptoms of estrogen deficiency) including functional hypothalamic amenorrhea (which may be suggested by a constellation of symptoms including restrictive eating patterns, excessive exercise, psychological stress, etc.)
Persistent hemoglobin < 11.5 g/dL for non-African American subjects; hemoglobin < 11.0 g/dL for African American subjects (confirmed on repeat). Importantly, documentation of a hemoglobin ≥ 11.0 g/dL for African American subjects or ≥ 11.5 g/dL for non-African American subjects in the month prior to the CRU admission is required for frequent sampling protocol in the CRU.
Severe thrombocytopenia (platelets < 50,000 cells/microliter) or leukopenia (total white blood count < 4,000 cells/microliter)
Previous diagnosis of diabetes, fasting glucose ≥ 126 mg/dl, or a hemoglobin A1c ≥ 6.5%
Persistently abnormal sodium or potassium concentration. Bicarbonate concentrations < 20 or > 30.
Liver test abnormalities, with two exceptions: (1) mild bilirubin elevations will be accepted in the setting of known Gilbert's syndrome or when the subject's primary care provider provides a presumptive diagnosis of Gilbert's syndrome and has no plans for further work-up; (2) mild transaminase (ALT, AST) elevations may be seen in obese/HA/PCOS girls, so stable elevations < 1.5 times the upper limit of normal will be accepted in this group.
Absolute contraindications to spironolactone use include history of allergy to spironolactone, anuria, acute renal insufficiency, significant impairment of renal excretory function, hyperkalemia, primary adrenal insufficiency (Addison's disease), and concomitant use of eplerenone
Significant history of cardiac or pulmonary dysfunction (e.g., known or suspected congestive heart failure, asthma requiring intermittent systemic corticosteroids, etc.)
Decreased renal function evidenced by GFR < 60 ml/min/1.73m2
History of cancer diagnosis and/or treatment (with the exception of basal cell or squamous cell skin carcinoma) unless they have remained clinically disease free (based on appropriate surveillance) for five years.

Study Design

Enrollment

32 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

experimental: Spironolactone

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

placebo comparator: Placebo

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

Interventions

Spironolactone

Spironolactone is an androgen-receptor blocker commonly used (off-label) for hyperandrogenism. The spironolactone dose will be 50 mg taken orally twice daily (for two weeks before admission to the Clinical Research Unit).

Placebo

Placebo contains only inert ingredients and is not expected to exert any direct physiological effects.

Primary outcome measure

Change in Sleep-Associated Luteinizing Hormone (LH) Pulse Frequency Between Admission With Spironolactone Versus Placebo [ Time Frame: Baseline to 2 months ]

Central Contacts and Locations

Central contacts

Melissa Gilrain, BS

434-243-6911 mg7zb@hscmail.mcc.virginia.edu

Christine Burt Solorzano, MD

434-243-6911 cmb6w@hscmail.mcc.virginia.edu

Locations

Center for Research in Reproduction, University of Virginia

Recruiting

Charlottesville, Virginia, United States, 22908

Contacts

Melissa Gilrain, BS

434-243-6911 pcos@virginia.edu

Christine M Burt Solorzano, MD

434-924-9084 pcos@virginia.edu

Principal Investigator:

Christine M Burt Solorzano, MD

More Information

Sponsor

University of Virginia

Last update posted

Aug 5, 2025

Last verified

Jul, 2025

Keywords

Hyperandrogenism
Polycystic ovary syndrome
Puberty

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Virginia on 2025-08-05.