Transcriptional and Epigenetic Program of PCOS Women

NCT ID: NCT04034706

Last Updated: 2025-03-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

ACTIVE_NOT_RECRUITING

Total Enrollment

108 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-01-31

Study Completion Date

2025-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

PCOS

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

PCOS females

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

DEXA

Intervention Type OTHER

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

Magnetic Resonance (MR) Assessment of the Abdomen

Intervention Type OTHER

Include measures to assess liver lipid content and stiffness and perform volumetric fat quantitation.

MR assessment of Whole Body Fat

Intervention Type OTHER

Volumetric measurement of fat, muscle and bone

Adipose tissue biopsy

Intervention Type PROCEDURE

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.

Oral glucose tolerance test

Intervention Type OTHER

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.

DEXA

Intervention Type OTHER

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

Magnetic Resonance (MR) Assessment of the Abdomen

Intervention Type OTHER

Include measures to assess liver lipid content and stiffness and perform volumetric fat quantitation.

MR assessment of Whole Body Fat

Intervention Type OTHER

Volumetric measurement of fat, muscle and bone

Adipose tissue biopsy

Intervention Type PROCEDURE

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.

Oral glucose tolerance test

Intervention Type OTHER

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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

DEXA

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

Intervention Type OTHER

Magnetic Resonance (MR) Assessment of the Abdomen

Include measures to assess liver lipid content and stiffness and perform volumetric fat quantitation.

Intervention Type OTHER

MR assessment of Whole Body Fat

Volumetric measurement of fat, muscle and bone

Intervention Type OTHER

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.

Intervention Type PROCEDURE

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.

Intervention Type OTHER

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

AdventHealth Translational Research Institute

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Steven Smith, MD

Role: PRINCIPAL_INVESTIGATOR

Principal Investigator

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

AdventHealth Translational Research Institute

Orlando, Florida, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

Abbott DH, Barnett DK, Bruns CM, Dumesic DA. Androgen excess fetal programming of female reproduction: a developmental aetiology for polycystic ovary syndrome? Hum Reprod Update. 2005 Jul-Aug;11(4):357-74. doi: 10.1093/humupd/dmi013.

Reference Type BACKGROUND
PMID: 15941725 (View on PubMed)

Abbott DH, Dumesic DA, Eisner JR, Colman RJ, Kemnitz JW. Insights into the development of polycystic ovary syndrome (PCOS) from studies of prenatally androgenized female rhesus monkeys. Trends Endocrinol Metab. 1998 Feb;9(2):62-7. doi: 10.1016/s1043-2760(98)00019-8.

Reference Type BACKGROUND
PMID: 18406243 (View on PubMed)

Azziz R, Carmina E, Chen Z, Dunaif A, Laven JS, Legro RS, Lizneva D, Natterson-Horowtiz B, Teede HJ, Yildiz BO. Polycystic ovary syndrome. Nat Rev Dis Primers. 2016 Aug 11;2:16057. doi: 10.1038/nrdp.2016.57.

Reference Type BACKGROUND
PMID: 27510637 (View on PubMed)

Barber TM, Golding SJ, Alvey C, Wass JA, Karpe F, Franks S, McCarthy MI. Global adiposity rather than abnormal regional fat distribution characterizes women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2008 Mar;93(3):999-1004. doi: 10.1210/jc.2007-2117. Epub 2007 Dec 18.

Reference Type BACKGROUND
PMID: 18089693 (View on PubMed)

Bjorntorp P. Adipose tissue distribution and function. Int J Obes. 1991 Sep;15 Suppl 2:67-81.

Reference Type BACKGROUND
PMID: 1794941 (View on PubMed)

Bos G, Snijder MB, Nijpels G, Dekker JM, Stehouwer CD, Bouter LM, Heine RJ, Jansen H. Opposite contributions of trunk and leg fat mass with plasma lipase activities: the Hoorn study. Obes Res. 2005 Oct;13(10):1817-23. doi: 10.1038/oby.2005.221.

Reference Type BACKGROUND
PMID: 16286530 (View on PubMed)

Ciaraldi TP, Aroda V, Mudaliar S, Chang RJ, Henry RR. Polycystic ovary syndrome is associated with tissue-specific differences in insulin resistance. J Clin Endocrinol Metab. 2009 Jan;94(1):157-63. doi: 10.1210/jc.2008-1492. Epub 2008 Oct 14.

Reference Type BACKGROUND
PMID: 18854391 (View on PubMed)

de Koning L, Merchant AT, Pogue J, Anand SS. Waist circumference and waist-to-hip ratio as predictors of cardiovascular events: meta-regression analysis of prospective studies. Eur Heart J. 2007 Apr;28(7):850-6. doi: 10.1093/eurheartj/ehm026. Epub 2007 Apr 2.

Reference Type BACKGROUND
PMID: 17403720 (View on PubMed)

Diamanti-Kandarakis E, Dunaif A. Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocr Rev. 2012 Dec;33(6):981-1030. doi: 10.1210/er.2011-1034. Epub 2012 Oct 12.

Reference Type BACKGROUND
PMID: 23065822 (View on PubMed)

Divoux A, Karastergiou K, Xie H, Guo W, Perera RJ, Fried SK, Smith SR. Identification of a novel lncRNA in gluteal adipose tissue and evidence for its positive effect on preadipocyte differentiation. Obesity (Silver Spring). 2014 Aug;22(8):1781-5. doi: 10.1002/oby.20793. Epub 2014 May 23.

Reference Type BACKGROUND
PMID: 24862299 (View on PubMed)

Elbers JM, Asscheman H, Seidell JC, Gooren LJ. Effects of sex steroid hormones on regional fat depots as assessed by magnetic resonance imaging in transsexuals. Am J Physiol. 1999 Feb;276(2):E317-25. doi: 10.1152/ajpendo.1999.276.2.E317.

Reference Type BACKGROUND
PMID: 9950792 (View on PubMed)

Elbers JM, Asscheman H, Seidell JC, Megens JA, Gooren LJ. Long-term testosterone administration increases visceral fat in female to male transsexuals. J Clin Endocrinol Metab. 1997 Jul;82(7):2044-7. doi: 10.1210/jcem.82.7.4078.

Reference Type BACKGROUND
PMID: 9215270 (View on PubMed)

Frayn KN. Adipose tissue as a buffer for daily lipid flux. Diabetologia. 2002 Sep;45(9):1201-10. doi: 10.1007/s00125-002-0873-y. Epub 2002 Jul 24.

Reference Type BACKGROUND
PMID: 12242452 (View on PubMed)

Guo Z, Johnson CM, Jensen MD. Regional lipolytic responses to isoproterenol in women. Am J Physiol. 1997 Jul;273(1 Pt 1):E108-12. doi: 10.1152/ajpendo.1997.273.1.E108.

Reference Type BACKGROUND
PMID: 9252486 (View on PubMed)

Horowitz JF, Klein S. Whole body and abdominal lipolytic sensitivity to epinephrine is suppressed in upper body obese women. Am J Physiol Endocrinol Metab. 2000 Jun;278(6):E1144-52. doi: 10.1152/ajpendo.2000.278.6.E1144.

Reference Type BACKGROUND
PMID: 10827018 (View on PubMed)

Jason J. Polycystic ovary syndrome in the United States: clinical visit rates, characteristics, and associated health care costs. Arch Intern Med. 2011 Jul 11;171(13):1209-11. doi: 10.1001/archinternmed.2011.288. No abstract available.

Reference Type BACKGROUND
PMID: 21747019 (View on PubMed)

Karastergiou K, Fried SK, Xie H, Lee MJ, Divoux A, Rosencrantz MA, Chang RJ, Smith SR. Distinct developmental signatures of human abdominal and gluteal subcutaneous adipose tissue depots. J Clin Endocrinol Metab. 2013 Jan;98(1):362-71. doi: 10.1210/jc.2012-2953. Epub 2012 Nov 12.

Reference Type BACKGROUND
PMID: 23150689 (View on PubMed)

Kirchengast S, Huber J. Body composition characteristics and body fat distribution in lean women with polycystic ovary syndrome. Hum Reprod. 2001 Jun;16(6):1255-60. doi: 10.1093/humrep/16.6.1255.

Reference Type BACKGROUND
PMID: 11387301 (View on PubMed)

Kokosar M, Benrick A, Perfilyev A, Fornes R, Nilsson E, Maliqueo M, Behre CJ, Sazonova A, Ohlsson C, Ling C, Stener-Victorin E. Epigenetic and Transcriptional Alterations in Human Adipose Tissue of Polycystic Ovary Syndrome. Sci Rep. 2016 Mar 15;6:22883. doi: 10.1038/srep22883.

Reference Type BACKGROUND
PMID: 26975253 (View on PubMed)

Lavebratt C, Almgren M, Ekstrom TJ. Epigenetic regulation in obesity. Int J Obes (Lond). 2012 Jun;36(6):757-65. doi: 10.1038/ijo.2011.178. Epub 2011 Sep 13.

Reference Type BACKGROUND
PMID: 21912396 (View on PubMed)

Manneras-Holm L, Leonhardt H, Kullberg J, Jennische E, Oden A, Holm G, Hellstrom M, Lonn L, Olivecrona G, Stener-Victorin E, Lonn M. Adipose tissue has aberrant morphology and function in PCOS: enlarged adipocytes and low serum adiponectin, but not circulating sex steroids, are strongly associated with insulin resistance. J Clin Endocrinol Metab. 2011 Feb;96(2):E304-11. doi: 10.1210/jc.2010-1290. Epub 2010 Nov 17.

Reference Type BACKGROUND
PMID: 21084397 (View on PubMed)

Manolopoulos KN, Karpe F, Frayn KN. Gluteofemoral body fat as a determinant of metabolic health. Int J Obes (Lond). 2010 Jun;34(6):949-59. doi: 10.1038/ijo.2009.286. Epub 2010 Jan 12.

Reference Type BACKGROUND
PMID: 20065965 (View on PubMed)

Whytock KL, Divoux A, Sun Y, Hopf M, Yeo RX, Pino MF, Yu G, Smith SR, Walsh MJ, Sparks LM. Isolation of nuclei from frozen human subcutaneous adipose tissue for full-length single-nuclei transcriptional profiling. STAR Protoc. 2023 Mar 17;4(1):102054. doi: 10.1016/j.xpro.2023.102054. Epub 2023 Jan 20.

Reference Type DERIVED
PMID: 36853719 (View on PubMed)

Related Links

Access external resources that provide additional context or updates about the study.

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

1354588

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.