Does Treatment of Androgen Excess Using Spironolactone Improve Ovulatory Rates in Girls With Androgen Excess?

NCT04075149 | Unknown Early Phase 1 DMC FDA Drug

• 1 other identifier: 21768
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Adolescent girls with androgen excess have a higher rate of irregular periods and decreased ovulation rates compared to normal girls, and are considered at-risk for developing polycystic ovary syndrome (PCOS). This pilot study will look at whether giving spironolactone might improve ovulation rates in girls with androgen excess, ages 13-19. If this is true, spironolactone treatment to young girls might prevent PCOS from developing and avoid future infertility.

Conditions

Polycystic Ovary Syndrome; Puberty Disorders; Ovulation Disorder

Keywords

PCOS; Polycystic Ovary Syndrome; ovulation; puberty; hyperandrogenemia; androgen excess

Outcome Measures

Primary Outcomes (1)

• Ovulation Rate Changes

  Ovulation rate during and after spironolactone compared to before medication. Ovulation will be counted based on salivary progesterone levels. The rate of ovulation will be defined as the number of ovulatory cycles per 100 days of follow-up.

  Rates of ovulation during weeks 17-32 (on medication) and weeks 33-48 (after medication) compared to weeks 1-16 (baseline, prior to medication)

Secondary Outcomes (3)

• Menstrual Regularity Changes

  IMI for weeks 1-16 (before medication, baseline), weeks 17-32 (on medication), and weeks 33-52 (after medication)

• Acne

  weeks 16 and 32

• Hirsutism

  weeks 16 and 32

Study Arms (1)

Spironolactone

EXPERIMENTAL

16 weeks without medication, then 16 weeks with medication, then 12 months without medication; spironolactone 50 mg tablets: 50-100 mg orally twice daily (1.7-3.3 mg/kg/24 hr)

Drug: Spironolactone

Interventions

Spironolactone DRUG

Spironolactone is an androgen-receptor commonly used (off-label) for hyperandrogenism in girls and women. It is used in this study to determine if androgen blockade can improve ovulation rates in girls with androgen excess, who often have low rates of ovulation in the years following menarche. The spironolactone dose will be as follows: If ≤ 60 kg, 50 mg twice daily; if \> 60 kg, 100 mg twice daily.

Also known as: Aldactone

Spironolactone

Eligibility Criteria

• Age: 13 Years - 19 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Girls age 13 - 19 years, with clinical or biochemical HA (defined as hirsutism and/or elevated Tanner stage-specific free testosterone concentrations) that are 4-6 years post-menarche
• Screening labs within age-appropriate normal range
• Volunteers who are 18-19 y old must be willing and able to provide written informed consent.
• When the subject is a minor (i.e., age \< 18 y), the subject and custodial parents must be willing and able to provide written informed assent and consent, respectively.
• Willingness to strictly avoid pregnancy (using non-hormonal methods) during the time of study.

You may not qualify if:

• Age \< 13 or \> 19 y
• Girls ≤ 3 years and ≥ 7 years post-menarche will be excluded
• Being a study of androgen excess in adolescent girls with HA, men and boys are excluded
• Inability to comprehend what will be done during the study or why it will be done
• Precocious puberty (breast development before age 7)
• Primary amenorrhea (no menses by age 16)
• BMI-for-age \< 5th percentile
• Patients currently enrolled in another research protocol will be excluded, except for those enrolled in IRB-HSR 17633 DENND1A
• Obesity due to genetic syndrome (e.g. Prader-Willi syndrome)
• Cushing syndrome
• Positive pregnancy test or 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 them to tell their parent(s) and counsel them about the importance of appropriate prenatal care and counseling. We will arrange follow-up for them at the Teen Health Clinic at the University of Virginia or their primary care physician's office in a timely manner.
• Diabetes mellitus
• History of congenital adrenal hyperplasia or 17-hydroxyprogesterone \> 300 ng/dL in the follicular phase, which suggests the possibility of congenital adrenal hyperplasia. NOTE: If a 17-hydroxyprogesterone \> 300 ng/dL is confirmed on repeat testing, and ACTH-stimulated 17-hydroxyprogesterone \< 1000 ng/dL will be required for study participation.
• Total testosterone \> 150 ng/dL
• Abnormal thyroid stimulating hormone (TSH) for age. Subjects with adequately treated hypothyroidism, reflected by normal TSH values, will not be excluded.

Sponsors & Collaborators

• University of Virginia: lead
• The Waterloo Foundation: collaborator

Study Sites (1)

University of Virginia Center for Research in Reproduction

Charlottesville, Virginia, 22908, United States

RECRUITING

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Hyperandrogenism

Interventions

Spironolactone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Christine Burt Solorzano, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Melissa Gilrain, BS

CONTACT

434-243-6911; pcos@virginia.edu

Christine Burt Solorzano, MD

CONTACT

434-243-6911; pcos@virginia.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Pediatrics

Model Details: non-randomized cross-sectional, before and after intervention

Study Record Dates

• First Submitted: August 29, 2019
• First Posted: August 30, 2019
• Study Start: December 18, 2019
• Primary Completion: September 1, 2024
• Study Completion: September 1, 2024
• Last Updated: October 27, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)