Transcriptional and Epigenetic Program of PCOS Women

Active, not recruiting

• Conditions: PCOS
• Interventions: Other: DEXA; Other: Magnetic Resonance (MR) Assessment of the Abdomen; Other: MR assessment of Whole Body Fat; Procedure: Adipose tissue biopsy; Other: Oral glucose tolerance test

• Registration Number: NCT04034706
• Lead Sponsor: AdventHealth Translational Research Institute

Brief Summary

The main goal is to reveal differences in global gene expression in two different adipose tissue (AT) depots of females with and without polycystic ovary syndrome (PCOS) and how these are influenced by upstream epigenetic markers

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-07-24
• Study First Submitted QC: 2019-07-24
• Study First Posted: 2019-07-26
• Study Start: 2020-01-31
• Primary Completion: 2023-04-12
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-12
• Last Update Posted: 2025-03-13
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 108

Inclusion Criteria

1. Women;
2. Age 18-45 years inclusive;
3. BMI 23-40 kg/m2 inclusive;
4. HbA1C ≤ 6.0% or fasting plasma glucose < 126 mg/dL;
5. Weight stable (± 3 kg) during the 3 months prior to enrollment;
6. Women must be > 9 months post-partum;
7. For PCOS: A documented history of PCOS from their physician according to the Androgen Excess (AE)-PCOS criteria: (defined by the presence of hyperandrogenism (clinical and/or biochemical), ovarian dysfunction (oligo-anovulation and/or polycystic ovaries), and the exclusion of related disorders (eg. hypoadrenalism, ovarian tumors)
8. Regular menstrual cycle for females without PCOS
9. Able to provide written, informed consent.

Exclusion Criteria

1. Postmenopausal women

2. Women with hysterectomy

3. Pregnancy, lactation or < 9 months postpartum from the scheduled date of screening.

4. Fasting plasma glucose > 126 mg/dL, or HbA1c > 6% or diagnosis with Type 2 Diabetes (T2D) or Type 1 Diabetes (T1D)

5. History or presence of cardiovascular disease (unstable angina, myocardial infarction or coronary revascularization within 6 months, clinically significant abnormalities on EKG), presence of cardiac pacemaker, implanted cardiac defibrillator.

6. Liver disease (AST or ALT >2.5 times the upper limit of normal)

7. Kidney disease (creatinine >1.6 mg/dl or estimated GFR <60 ml/min)

8. Dyslipidemia, including triglycerides >500 mg/dl, LDL >200 mg/dl

9. Anemia (hemoglobin <11 g/dl)

10. Thyroid dysfunction (suppressed thyroid-stimulating hormone, elevated TSH <10 µIU/ml if symptomatic or elevated TSH >10 µIU/ml if asymptomatic)

11. Uncontrolled hypertension (BP >160 mmHg systolic or >100 mmHg diastolic)

12. Elevated hsCRP or known active infection

13. History of cancer within the last 5 years (skin cancers, with the exception of melanoma, may be acceptable)

14. History of drug or alcohol abuse (> 3 drinks per day) within the last 5 years. Current drug use may be determined by plasma or urine drug screens.

15. psychiatric disease prohibiting adherence to study protocol.

16. History of organ transplant.

17. Known history of HIV, active Hepatitis A, B or C or tuberculosis.

18. History of bariatric surgery.

19. Current smokers (smoking within the past 3 months).

20. Current use of beta-adrenergic blocking agents.

21. Use of oral or injectable anti-hyperglycemic agents: metformin, sulfonylureas, DPP IV inhibitors, SGLT-2 inhibitors, thiazolidinediones, acarbose, GLP-1 analogs and insulin unless willing to undertake a washout period of 15 days for metformin and GLP-1 analogs and undergo subsequent laboratory screening tests.

22. Gonadotropin Releasing Hormone (GnRH) and/or Antiandrogen use within the last 2 months.

23. Use of any medications known to influence fat and/or energy metabolism (eg growth hormone therapy, glucocorticoids [steroids], etc.)

24. Initiation or change in hormone replacement therapy within the past 3 months (including, but not limited to thyroid hormone, estrogen replacement therapy or In Vitro Fertilization therapy).

25. Current treatment with blood thinners or antiplatelet medications that cannot be safely stopped for biopsy and testing procedures.

26. Not able or willing to have DXA scans or are above the acceptable weight limit (450 lbs) of the DXA scanner.

27. Presence of any condition that, in the opinion of the Investigators, compromises participant safety or data integrity or the participant's ability to complete study visits.

28. Not able to participate in MRI assessments due to:

    1. Metal implants (pacemaker, non-removable body piercings, aneurysm clips) based on Investigator's judgment at screening
    2. Physical limitations or equipment tolerances (e.g., MRI bore size) based on Investigator's judgment at screening
    3. Inability to tolerate MRI imaging without sedation or claustrophobia

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
PCOS females	Oral glucose tolerance test	Females diagnosed with PCOS with a BMI between 23 and 40 kg/m2.
Non-PCOS control females	Magnetic Resonance (MR) Assessment of the Abdomen	Females without PCOS with a BMI between 23 and 40 kg/m2 split into 2 groups- apple shaped and pear shaped.
Non-PCOS control females	MR assessment of Whole Body Fat	Females without PCOS with a BMI between 23 and 40 kg/m2 split into 2 groups- apple shaped and pear shaped.
PCOS females	DEXA	Females diagnosed with PCOS with a BMI between 23 and 40 kg/m2.
PCOS females	Magnetic Resonance (MR) Assessment of the Abdomen	Females diagnosed with PCOS with a BMI between 23 and 40 kg/m2.
PCOS females	MR assessment of Whole Body Fat	Females diagnosed with PCOS with a BMI between 23 and 40 kg/m2.
PCOS females	Adipose tissue biopsy	Females diagnosed with PCOS with a BMI between 23 and 40 kg/m2.
Non-PCOS control females	Oral glucose tolerance test	Females without PCOS with a BMI between 23 and 40 kg/m2 split into 2 groups- apple shaped and pear shaped.
Non-PCOS control females	DEXA	Females without PCOS with a BMI between 23 and 40 kg/m2 split into 2 groups- apple shaped and pear shaped.
Non-PCOS control females	Adipose tissue biopsy	Females without PCOS with a BMI between 23 and 40 kg/m2 split into 2 groups- apple shaped and pear shaped.

Primary Outcome Measures

Name	Time	Method
Epigenomic and transcriptomic differences in abdominal vs gluteal subcutaneous adipose tissue between females with and without polycystic ovary syndrome	6 months after the last participant will be enrolled	Epigenetic profiles (DNA methylation) and gene expression (RNA-seq) will be performed on whole tissue abdominal fat and gluteofemoral fat biopsies in addition to cultured pre-adipocytes and adipocytes.

Trial Locations

Locations (1)

AdventHealth Translational Research Institute; 🇺🇸 Orlando, Florida, United States