Blood Vessel Function in Adolescents and Women With Polycystic Ovary Syndrome

NCT ID: NCT01615562

Last Updated: 2015-12-14

Basic Information

• Recruitment Status: TERMINATED
• Total Enrollment: 18 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2011-12-31
• Study Completion Date: 2015-07-31

Brief Summary

The purpose of this study is to determine if changes in blood vessel health lead to the menstrual irregularities that women with PCOS experience. This research study will help determine if women with PCOS have early changes in their blood vessels called "endothelial dysfunction," and if the number of progenitor cells (cells that in a healthy person repair blood vessel damage) are related to these blood vessel changes. To do so, we will compare ultrasound (soundwave) pictures of a large blood vessel in the arm and the results of blood tests between women with PCOS and other healthy women with normal menstrual periods.

Detailed Description

Overview:

Although adult women with PCOS demonstrate evidence of endothelial dysfunction, little is known regarding alterations in the number of pro-inflammatory monocytes, CEC, CPC, and ECFC (endothelial injury/repair profile) among affected women. For many women, the clinical manifestations of PCOS emerge during adolescence. Based on studies documenting the increased prevalence of MetS and inflammatory markers in adolescent girls with PCOS, and non-invasive studies documenting the presence of endothelial dysfunction in children with traditional cardiovascular risk factors, it is likely adolescent girls with PCOS already manifest evidence of early vascular dysfunction, which may in turn impair follicular development and contribute to the development of infertility.

Consequently, we hypothesize that perturbations in the balance between circulating inflammatory and progenitor cells contribute to the endothelial dysfunction observed in adult women with PCOS. Specifically, we anticipate that PCOS women will manifest greater evidence of vascular injury (increased numbers of inflammatory monocytes, CEC, and ECFC) and impaired endothelial repair (decreased levels of CPC) compared with control women. Moreover, we propose that, in adolescent girls with PCOS, endothelial dysfunction and corresponding alterations in the endothelial injury/repair profile are already present.

Specific Aim 1: Determine if the endothelial injury/repair profile (inflammatory monocytes, CEC, CPC, and ECFC) assessed by flow cytometry (PFC) and endothelial function (assessed by flow-mediated vasodilation (FMD) of the brachial artery) are altered in treatment-naïve adult (18-40 years of age) women with PCOS (n=15) compared with age and body mass index (BMI)-matched control women (n=15).

Specific Aim 2: Determine if the endothelial injury/repair profile assessed by PFC, AGE levels, and endothelial function (assessed by FMD of the brachial artery) are altered in treatment-naïve adolescents (14-17 years of age) with PCOS (n=15) compared with age and BMI-Z-score-matched control girls (n=15).

Specific Aim 3: Determine if observed alterations in the endothelial injury/repair profile (pro-inflammatory monocytes, CEC, CPC and ECFC) or levels of AGE correlate with endothelial function (assessed by FMD of the brachial artery) in adolescent and adult women with (n=30) and without PCOS (n=30), and whether androgens, insulin resistance, or other cardiovascular risk factors influence these relationships.

This is a cross-sectional study design involving 30 post-menarchal adolescents and 30 adult female subjects. Specifically, the adolescent population will include 15 treatment-naïve adolescent females (ages 14-17 years) with PCOS and 15 age- and BMI-percentile-matched control adolescent subjects. Similarly, the adult study population will include 15 treatment-naïve adult females (ages 18-40 years) with PCOS and 15 age- and BMI-matched control women. All study procedures will be conducted at the Clinical Research Services Unit (CRSU) at Virginia Commonwealth University (VCU) during a single visit (~3.5 hrs).

CRSU Visit:

Subjects will be admitted to the CRSU after a 12-hour overnight fast. Subjects will also be instructed to refrain from vigorous physical activity for 24 hours prior to the visit. All participants will undergo a detailed medical history (including a menstrual history) and a complete physical examination (including assessments of Tanner Staging for breast and pubic hair development). Hirsutism will be assessed using the modified Ferriman-Gallwey scoring system.

At the study visit, the following anthropometric measurements with be performed on all subjects:

• Blood pressure obtained in left arm - 3 readings at 5 minute intervals
• Pulse
• Temperature
• Height (2 measurements)
• Weight (2 measurements)
• Waist/umbilicus/hip circumference measurements (2 measurements)
• Bioimpedence

At the study visit a resting electrocardiogram (ECG) will be obtained for all subjects.

At the study visit, the following labs will be obtained on all subjects:

• Comprehensive metabolic panel
• Lipid panel
• Urine pregnancy
• TSH*
• Prolactin*
• 17-hydroxyprogesterone*
• Testosterone* *These analyses are to be performed only when additional eligibility screening is needed and only at PI request.

All subjects will undergo measurement of brachial artery flow-mediated vasodilation (FMD). FMD testing will be performed by the PI or Co-Investigator in the CRSU Peripheral Vascular Lab with the assistance of a trained technician using an ultrasound peripheral vascular imaging system. Adult subjects only will also undergo brachial artery reactivity testing for the assessment of non-endothelial dependent (NED) vessel dilation following the administration of nitroglycerin. NED testing will be performed following a rest period of at least 15 minutes from completion of the FMD testing. 400 μg of nitroglycerin will be administered sublingually, and images will be recorded for at least 3 minutes following the administration of nitroglycerin.

Following the FMD testing (allow 30 minute interval), all subjects are to undergo a 2-hour 75 g oral glucose tolerance test.

• Samples collected at baseline (-15 and 0) and 30 minute intervals for glucose, insulin

Conditions

Polycystic Ovary Syndrome (PCOS)

Keywords

Polycystic Ovary Syndrome; PCOS; Infertility

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

PCOS adolescents

Post-menarchal females ages 14-17 with and without PCOS (15 each group for a total of 30 subjects).

No interventions assigned to this group

PCOS women

Women ages 18-40 with and without PCOS (15 each group for a total of 30 subjects).

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• PCOS as defined by NIH/NICHD criteria: 1) oligo- or amenorrhea (≤8 menstrual periods annually, persisting 2 years post menarche); 2) biochemical hyperandrogenism(HA), i.e.,elevated total or free testosterone concentration and/or clinical evidence of HA (defined as the presence of hirsutism); and 3) exclusion of secondary causes of ovulatory dysfunction and HA (including hyperprolactinemia, thyroid dysfunction, non-classical congenital adrenal hyperplasia (NCAH) due to 21-hydroxylase deficiency, Cushing syndrome, androgen secreting neoplasms, and androgenic/anabolic drug use).

Exclusion Criteria

• Diabetes mellitus
• Underlying endocrine, neurologic, and/or genetic syndromes leading to obesity
• Congenital heart disease or abnormal resting ECG
• Renal or hepatic disease
• History of rheumatologic disorders or malignancy
• Use of medications or dietary supplements known to affect insulin sensitivity (i.e. metformin, corticosteroids, and oral contraceptive pills), blood pressure, or cholesterol within 3 months of study participation
• Investigation drug use within 3 months of study participation
• Pregnancy
• Current tobacco use

• Minimum Eligible Age: 14 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

Virginia Commonwealth University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Edmond Wickham, MD

Role: PRINCIPAL_INVESTIGATOR

Virginia Commonwealth University

Locations

Virginia Commonwealth University

Richmond, Virginia, United States

Countries

United States

Related Links

http://www.vcu.edu/pcos/research.html

VCU PCOS Research Site

Other Identifiers

U54HD034449

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U54HD034449- Wickham Pilot

Identifier Type: -

Identifier Source: org_study_id