Clinical trial NCT04034706: Transcriptional and Epigenetic Program of PCOS Women
Official title: Transcriptional and Epigenetic Program of PCOS Women
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: PCOS
Lead sponsor: AdventHealth Translational Research Institute
Sponsor class: OTHER
First posted: 2019-07-26
Enrollment: 108
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Recruitment methods utilized may include, but will not be limited to, the following: recruitment from within the AdventHealth Translational Research Institute's patient population: electronic medical records and database searches (including third party recruitment vendors); advertising in multiple media such as print ads, flyers, brochures, posters; radio ads; television spots; and internet/social media advertising.

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


Eligibility criteria: 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

Primary outcomes:
measure: Epigenomic and transcriptomic differences in abdominal vs gluteal subcutaneous adipose tissue between females with and without polycystic ovary syndrome
timeFrame: 6 months after the last participant will be enrolled
Secondary outcomes:
Other outcomes:
Locations:
city: Orlando
country: United States
facility: AdventHealth Translational Research Institute
state: Florida
Study officials:
affiliation: Principal Investigator
name: Steven Smith, MD
role: PRINCIPAL_INVESTIGATOR
References:
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