Transcriptional and Epigenetic Program of PCOS Women

NCT04034706 | Active Not Recruiting

• 1 other identifier: 1354588
• Study Type: observational
• Target: 108
• Locations: 1 country
• Sites: 1

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

Conditions

PCOS

Outcome Measures

Primary Outcomes (1)

• Epigenomic and transcriptomic differences in abdominal vs gluteal subcutaneous adipose tissue between females with and without polycystic ovary syndrome

  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.

  6 months after the last participant will be enrolled

Study Arms (2)

PCOS females

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

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

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

Interventions

DEXA OTHER

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

Non-PCOS control females; PCOS females

Magnetic Resonance (MR) Assessment of the Abdomen OTHER

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

Non-PCOS control females; PCOS females

MR assessment of Whole Body Fat OTHER

Volumetric measurement of fat, muscle and bone

Non-PCOS control females; PCOS females

Adipose tissue biopsy 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.

Non-PCOS control females; PCOS females

Oral glucose tolerance test 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; PCOS females

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• 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.

You may qualify if:

• Women;
• Age 18-45 years inclusive;
• BMI 23-40 kg/m2 inclusive;
• HbA1C ≤ 6.0% or fasting plasma glucose \< 126 mg/dL;
• Weight stable (± 3 kg) during the 3 months prior to enrollment;
• Women must be \> 9 months post-partum;
• Regular menstrual cycle for females without PCOS
• Able to provide written, informed consent.

You may not qualify if:

• Postmenopausal women
• Women with hysterectomy
• Pregnancy, lactation or \< 9 months postpartum from the scheduled date of screening.
• Fasting plasma glucose \> 126 mg/dL, or HbA1c \> 6% or diagnosis with Type 2 Diabetes (T2D) or Type 1 Diabetes (T1D)
• 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.
• Liver disease (AST or ALT \>2.5 times the upper limit of normal)
• Kidney disease (creatinine \>1.6 mg/dl or estimated GFR \<60 ml/min)
• Dyslipidemia, including triglycerides \>500 mg/dl, LDL \>200 mg/dl
• Anemia (hemoglobin \<11 g/dl)
• Thyroid dysfunction (suppressed thyroid-stimulating hormone, elevated TSH \<10 µIU/ml if symptomatic or elevated TSH \>10 µIU/ml if asymptomatic)
• Uncontrolled hypertension (BP \>160 mmHg systolic or \>100 mmHg diastolic)
• Elevated hsCRP or known active infection
• History of cancer within the last 5 years (skin cancers, with the exception of melanoma, may be acceptable)
• 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.
• psychiatric disease prohibiting adherence to study protocol.

Sponsors & Collaborators

• AdventHealth Translational Research Institute: lead

Study Sites (1)

AdventHealth Translational Research Institute

Orlando, Florida, 32804, United States

Location

Related Publications (23)

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  PMID: 15941725 BACKGROUND

• 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.

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• 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.

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

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• 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.

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• 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.

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• 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.

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• 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.

  PMID: 23065822 BACKGROUND

• 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.

  PMID: 24862299 BACKGROUND

• 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.

  PMID: 9950792 BACKGROUND

• 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.

  PMID: 9215270 BACKGROUND

• 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.

  PMID: 12242452 BACKGROUND

• 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.

  PMID: 9252486 BACKGROUND

• 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.

  PMID: 10827018 BACKGROUND

• 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.

  PMID: 21747019 BACKGROUND

• 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.

  PMID: 23150689 BACKGROUND

• 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.

  PMID: 11387301 BACKGROUND

• 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.

  PMID: 26975253 BACKGROUND

• 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.

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• 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.

  PMID: 21084397 BACKGROUND

• 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.

  PMID: 20065965 BACKGROUND

• 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.

  PMID: 36853719 DERIVED

Related Links

• Website for AdventHealth Translational Research Institute

MeSH Terms

Interventions

Magnetic Resonance Spectroscopy; Glucose Tolerance Test

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine

Study Officials

• Steven Smith, MD

  Principal Investigator

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2019
• First Posted: July 26, 2019
• Study Start: January 31, 2020
• Primary Completion: April 12, 2023
• Study Completion: December 1, 2025
• Last Updated: March 13, 2025

Record last verified: 2025-03

Locations

US (1)