Hyperandrogenemia and Altered Day-night LH Pulse Patterns

NCT03068910 | Recruiting Early Phase 1 DMC FDA Drug

• 2 other identifiers: 18489P50HD028934
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if, in mid- to late pubertal girls with hyperandrogenism, androgen-receptor blockade (spironolactone) improves the ability of progesterone to acutely reduce waking luteinizing hormone pulse frequency (primary endpoint).

Conditions

Hyperandrogenism; Polycystic Ovary Syndrome; Puberty

Keywords

Hyperandrogenism; Polycystic ovary syndrome; Puberty

Outcome Measures

Primary Outcomes (1)

• Luteinizing hormone (LH) pulse frequency

  LH pulse frequency while awake vs. while asleep

  During first CRU admission and during the second CRU admission (which occurs at least 2 months after the first)

Study Arms (2)

Spironolactone

EXPERIMENTAL

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

Drug: Micronized progesterone; Drug: Placebo

Placebo

PLACEBO COMPARATOR

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

Drug: Spironolactone; Drug: Placebo

Interventions

Micronized progesterone DRUG

Micronized progesterone 0.8 mg/kg at 0700, 1500, 2300 and 0700 h. Progesterone is a natural hormone.

Spironolactone

Spironolactone DRUG

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 DRUG

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

Placebo; Spironolactone

Eligibility Criteria

• Age: 10 Years - 17 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Mid- to late pubertal adolescent girl (at least Tanner breast stage 3, but no more than 2 years postmenarcheal)
• Hyperandrogenism, defined as a serum (calculated) free testosterone concentration greater than the Tanner stage-specific reference range and/or unequivocal evidence for hirsutism
• General good health (excepting overweight, obesity, hyperandrogenism, and adequately-treated hypothyroidism)
• Capable of and willing to provide informed assent (adolescents under age 16 years) and/or consent (adolescents over age 16 years; custodial parents or guardians of all adolescent volunteers)
• Willing to strictly avoid pregnancy with use of reliable non-hormonal methods during the study period

You may not qualify if:

• Inability/incapacity to provide informed consent
• Males will be excluded (hyperandrogenism is unique to females)
• Obesity resulting from a well-defined endocrinopathy or genetic syndrome
• Positive pregnancy test or current lactation
• 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 \> 200 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-hydroxyprogesterone \> 200 ng/dl is confirmed on repeat testing, an ACTH stimulated 17-hydroxyprogesterone \< 1000 ng/dl will be required for study participation.
• Abnormal thyroid stimulating hormone (TSH): Note that subjects with stable and adequately treated primary hypothyroidism, reflected by normal TSH values, will not be excluded.
• Hyperprolactinemia \> 20% higher than the upper limit of normal. Mild prolactin elevations may be seen in adolescents and women with HA/PCOS, and elevations within 20% higher than the upper limit of normal will be accepted in this group.
• 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 hematocrit \< 36% and hemoglobin \< 12 g/dl.
• Severe thrombocytopenia (platelets \< 50,000 cells/microliter) or leukopenia (total white blood count \< 4,000 cells/microliter)

Sponsors & Collaborators

• University of Virginia: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

University of Virginia Clinical Research Unit

Charlottesville, Virginia, 22908, United States

RECRUITING

MeSH Terms

Conditions

Hyperandrogenism; Polycystic Ovary Syndrome

Interventions

Progesterone; Spironolactone

Condition Hierarchy (Ancestors)

46, XX Disorders of Sex Development; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Adrenogenital Syndrome; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Gonadal Disorders; Endocrine System Diseases; Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Diseases

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Corpus Luteum Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones; Lactones; Organic Chemicals

Study Officials

• Christine Burt Solorzano, M.D.

  University of Virginia Center for Research in Reproduction

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Melissa Gilrain, MS

CONTACT

434-243-6911; mg7zb@uvahealth.org

Christine Burt Solorzano, M.D.

CONTACT

434-243-6911; cmb6w@uvahealth.org

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Treatment allocation will be double-blinded. The blind will be broken in the event of substantial adverse effects that would also lead to study withdrawal. The blind for a given subject will be lifted after the subject completes the study and analysis is complete for that subject.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr., MD

Model Details: Randomized, placebo-controlled, crossover study

Study Record Dates

• First Submitted: February 23, 2017
• First Posted: March 3, 2017
• Study Start: July 21, 2016
• Primary Completion: October 1, 2025
• Study Completion: December 1, 2025
• Last Updated: August 5, 2025

Record last verified: 2025-07

Locations

US (1)