Recruiting

Early Phase 1

Androgen Blockade & ProgesteroneAndrogen Blockade and Progesterone Augmentation of Gonadotropin Secretion

Sponsor:

University of Virginia

Code:

NCT04597099

Conditions

PCOS

Polycystic Ovary Syndrome

Eligibility Criteria

Sex: Female

Age: 18 - 30

Healthy Volunteers: Accepted

Interventions

Micronized progesterone

Placebo

Flutamide

Estradiol patch

Study Details

Brief summary:

This study is trying to find out if flutamide (a medication that blocks the effects of testosterone) may help normalize an aspect of pituitary function (specifically, gonadotropin surge generation) in PCOS. This is a randomized, placebo-controlled, double-blinded, crossover study. The investigators hypothesize that in estradiol-pretreated women with PCOS, acute progesterone augmentation of FSH release (positive feedback) will be enhanced by flutamide.

Conditions

PCOS

Polycystic Ovary Syndrome

Study ID

NCT04597099

Start date

Oct 26, 2022

Status verified date

Nov, 2023

Completion date

Oct 1, 2025

Anticipated

Primary completion date

Oct 1, 2025

Anticipated

Eligibility Criteria

Sex: Female

Age: 18 - 30

Healthy Volunteers: Accepted

Inclusion Criteria:

Post-pubertal (> 4 years post-menarche) adult woman aged 18-30 years
PCOS, defined as clinical and/or laboratory evidence of hyperandrogenism (hirsutism and/or elevated serum \[calculated\] free testosterone concentration) plus ovulatory dysfunction (irregular menses, fewer than 9 per year), but without evidence for other potential causes of hyperandrogenism and/or ovulatory dysfunction
General good health (excepting overweight, obesity, hyperandrogenism, PCOS, and adequately-treated hypothyroidism)
Capable of and willing to provide informed consent
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 (PCOS is unique to females)
Age < 18 years or > 30 years (ovarian reserve may decrease beyond age 30)
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 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 performed by the subject's personal physician 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 women with 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 < 37% and hemoglobin < 12 g/dl
Severe thrombocytopenia (platelets < 50,000 cells/microliter) or leukopenia (total white blood count < 4,000 cells/microliter)
Previous diagnosis of diabetes, fasting glucose > or = 126 mg/dl, or a hemoglobin A1c > or = 6.5%
Given that this study involves flutamide use, any liver panel abnormality will be grounds for exclusion
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
A personal history of breast, ovarian, or endometrial cancer
History of allergy to micronized progesterone, flutamide, or transdermal estradiol
BMI < 18 or > 40 kg/m2
Due to the amount of blood being drawn, volunteers with body weight < 110 pounds must be excluded

Study Design

Enrollment

10 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

experimental: Flutamide

Prior to the first or second admission (randomly determined), subjects will be pretreated for 4 weeks with Flutamide (250 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

Micronized progesterone

oral micronized progesterone suspension, 100 mg oral dose at 0800 during each study admission

Placebo

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

Flutamide

Flutamide, 250 mg taken orally twice daily for four weeks before study admission.

Estradiol patch

Two 0.1 mg/day transdermal estradiol patches will be applied 3 days prior to each inpatient admission; on the morning of study admission, these two patches will be removed and immediately replaced with two new 0.1 mg/day patches.

Primary outcome measure

Change in mean FSH concentration with progesterone administration [ Time Frame: After 4 weeks of placebo administration ]
Change in mean FSH concentration with progesterone administration [ Time Frame: After 4 weeks of flutamide administration ]

Central Contacts and Locations

Central contacts

Melissa Gilrain, BS

4342436911 pcos@virginia.edu

Locations

University of Virginia

Recruiting

Charlottesville, Virginia, United States, 22901

Contacts

Melissa Gilrain, BS

434-243-6911 pcos@virginia.edu

Christopher M McCartney, MD

434-243-6911 cm2hq@virginia.edu

Principal Investigator:

Christopher M McCartney, MD

More Information

Sponsor

University of Virginia

Last update posted

Nov 2, 2023

Last verified

Nov, 2023

Keywords

PCOS
Polycystic Ovary Syndrome

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-13. This information was provided to ClinicalTrials.gov by University of Virginia on 2023-11-02.