Does Spironolactone Normalize Sleep-wake Luteinizing Hormone Pulse Frequency in Pubertal Girls With Hyperandrogenism? — CBS010  

Polycystic Ovary Syndrome Clinical Trial

Official title: Does Spironolactone Normalize Sleep-wake Luteinizing Hormone (LH) Pulse Frequency in Pubertal Girls With Hyperandrogenism? (CBS010)

Status Recruiting

Clinical Trial 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).

Clinical Trial Description

This is a randomized, placebo-controlled, double-blinded crossover study to test the following hypothesis: In mid- to late pubertal girls with hyperandrogenism, spironolactone (50 mg twice daily) for 2 weeks will reduce sleep-associated luteinizing hormone (LH) pulse frequency compared to placebo treatment. To test this hypothesis, 16 late pubertal girls (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], but no more than 4 years post-menarcheal) with hyperandrogenism (serum [calculated] free testosterone concentration greater than the Tanner stage-specific reference range and/or clinical hirsutism) will undergo two clinical research unit (CRU) admissions separated by at least 4 weeks. During each admission, blood will be obtained every 10 minutes through an indwelling IV catheter from 1600 to 0700 h. This will allow full characterization of pulsatile LH secretion in addition to other hormone measurements. Formal polysomnography will be performed during CRU admissions. Subjects will be randomized to be pretreated for 2 weeks with either spironolactone (an androgen receptor blocker commonly used for hyperandrogenism) or placebo prior to the first admission; subjects will be pretreated with the other medication (placebo or spironolactone) for 2 weeks before the second admission in accordance with a cross-over design. The primary endpoint is LH pulse frequency while asleep. (LH pulse frequency while awake is an important secondary endpoint). The sleep-associated LH pulse frequency data from the spironolactone and placebo admissions will be analyzed via a hierarchical linear mixed model (HLMM). Secondary endpoints will include the relationships between sleep stages and LH pulse initiation (analyzed as per Lu et al., Neuroendocrinology 2018 [Epub ahead of print - doi: 10.1159/000488110]), and we will test the following hypothesis: In mid- to late pubertal girls with hyperandrogenism, spironolactone will enhance the ability of rapid eye movement (REM) sleep to inhibit LH pulse initiation. ;

Related Conditions & MeSH terms

• Hyperandrogenism
• Polycystic Ovary Syndrome
• Puberty

• NCT number: NCT04723862
• Study type: Interventional
• Source: University of Virginia
• Contact: Melissa Gilrain, BS
• Phone: 434-243-6911
• Email: mg7zb@hscmail.mcc.virginia.edu
• Status: Recruiting
• Phase: Early Phase 1
• Start date: November 12, 2021
• Completion date: October 1, 2025