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EPIC: Transcriptional and Epigenetic Program of PCOS Women

Sponsor
AdventHealth Translational Research Institute (Other)
Overall Status
Recruiting
CT.gov ID
NCT04034706
Collaborator
(none)
50
Enrollment
1
Location
34
Anticipated Duration (Months)
1.5
Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease Intervention/Treatment Phase
  • 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

Study Design

Study Type:
Observational
Anticipated Enrollment :
50 participants
Observational Model:
Cohort
Time Perspective:
Prospective
Official Title:
Transcriptional and Epigenetic Program of PCOS Women
Actual Study Start Date :
Jan 31, 2020
Anticipated Primary Completion Date :
Dec 1, 2022
Anticipated Study Completion Date :
Dec 1, 2022

Arms and Interventions

Arm Intervention/Treatment
PCOS females

Females diagnosed with PCOS with a BMI between 23 and 40 kg/m2.

Other: DEXA
DEXA Scans will be performed to measure body fat and estimate muscle mass using a General Electric Lunar iDXA whole-body scanner.

Other: Magnetic Resonance (MR) Assessment of the Abdomen
Include measures to assess liver lipid content and stiffness and perform volumetric fat quantitation.

Other: MR assessment of Whole Body Fat
Volumetric measurement of fat, muscle and bone

Procedure: Adipose tissue biopsy
0.5 cm incision of the upper-outer right vastus lateralis, and either a 3-4mm Mercedes Liposuction needle, or a 4-6 mm Bergstrom needle will be inserted to aspirate approximately 7 grams of adipose tissue.

Other: Oral glucose tolerance test
Glucose tolerance will be assessed with a 75 g oral glucose tolerance test (OGTT). Subjects will be studied after an overnight fast.
Non-PCOS control females

Females without PCOS with a BMI between 23 and 40 kg/m2 split into 2 groups- apple shaped and pear shaped.

Other: DEXA
DEXA Scans will be performed to measure body fat and estimate muscle mass using a General Electric Lunar iDXA whole-body scanner.

Other: Magnetic Resonance (MR) Assessment of the Abdomen
Include measures to assess liver lipid content and stiffness and perform volumetric fat quantitation.

Other: MR assessment of Whole Body Fat
Volumetric measurement of fat, muscle and bone

Procedure: Adipose tissue biopsy
0.5 cm incision of the upper-outer right vastus lateralis, and either a 3-4mm Mercedes Liposuction needle, or a 4-6 mm Bergstrom needle will be inserted to aspirate approximately 7 grams of adipose tissue.

Other: Oral glucose tolerance test
Glucose tolerance will be assessed with a 75 g oral glucose tolerance test (OGTT). Subjects will be studied after an overnight fast.

Outcome Measures

Primary Outcome Measures

  1. 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 45 Years
Sexes Eligible for Study:
Female
Accepts Healthy Volunteers:
Yes
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:

  29. Metal implants (pacemaker, non-removable body piercings, aneurysm clips) based on Investigator's judgment at screening

  30. Physical limitations or equipment tolerances (e.g., MRI bore size) based on Investigator's judgment at screening

  31. Inability to tolerate MRI imaging without sedation or claustrophobia

Contacts and Locations

Locations

Site City State Country Postal Code
1 AdventHealth Translational Research Institute Orlando Florida United States 32804

Sponsors and Collaborators

  • AdventHealth Translational Research Institute

Investigators

  • Principal Investigator: Steven Smith, MD, Principal Investigator

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

Responsible Party:
AdventHealth Translational Research Institute
ClinicalTrials.gov Identifier:
NCT04034706
Other Study ID Numbers:
  • 1354588
First Posted:
Jul 26, 2019
Last Update Posted:
Aug 3, 2022
Last Verified:
Aug 1, 2022
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No

Study Results

No Results Posted as of Aug 3, 2022