Pro-vascular Regenerative Cell Exhaustion in Women With Polycystic Ovarian Syndrome

NCT05410834 | Unknown

• 1 other identifier: Pro00063366
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

PCOS-RCE is an observational, cross-sectional, two-arm study that is aimed at determining if an established diagnosis of polycystic ovarian syndrome (PCOS) influences the number of blood vessel-forming stem cells in the bloodstream. Circulating progenitor cells will be enumerated and the distribution patterns of these cell types will be assessed to determine if these parameters differ between individuals with PCOS and individuals without PCOS. Specifically, this study will evaluate if differential regenerative cell exhaustion (RCE) may account, at least in part, for the differences in cardiovascular risk reported between individuals with a diagnosis of PCOS and those without.

Conditions

Polycystic Ovary Syndrome

Keywords

Polycystic ovarian syndrome; Progenitor cells; Women's Health; Insulin resistance; Chronic disease

Outcome Measures

Primary Outcomes (1)

• Frequency of circulating ALDHhiSSChi granulocytes

  Difference in the frequency of circulating ALDHhi SSChi granulocytes between women with PCOS versus without PCOS

  Baseline

Secondary Outcomes (2)

• Number of circulating ALDHhiSSCmid monocytes

  Baseline

• Number of circulating ALDHhiSSClo primitive progenitor cells

  Baseline

Study Arms (2)

Individuals with polycystic ovarian syndrome

Individuals with a documented diagnosis of polycystic ovarian syndrome

Individuals without polycystic ovarian syndrome

Individuals without a known diagnosis of polycystic ovarian syndrome but with regular menstrual cycles

Eligibility Criteria

• Age: 30 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants will be identified from primary care clinics in the Greater Toronto Area using paper-based and electronic medical records.

You may qualify if:

• Capable and willing to provide informed consent
• Females aged 30 and above
• Must meet criteria for one of the following two groups:
• Documented diagnosis of PCOS OR
• Normal and regular menstrual cycles with no known diagnosis of PCOS

You may not qualify if:

• Menopause, as defined by 12 months of amenorrhea
• Known causes of irregular menstrual bleeding caused by conditions other than PCOS
• Known secondary causes of ovulatory dysfunction and/or hyperandrogenism
• Current pregnancy, active lactation, or less than 6 months postpartum
• Ongoing treatment with ovulation-inducing medication
• History of hysterectomy and/or bilateral oophorectomy
• Severe congestive heart failure (as defined by New York Heart Association - class IV)
• Any life-threatening disease expected to result in death within the next 2 years
• Any malignancy not considered cured. A subject is considered cured if there has been no evidence of cancer recurrence for the 5 years prior to screening.
• Known severe liver disease
• Known acquired immunodeficiency syndrome such as HIV
• Current treatment with systemic or oral corticosteroid therapy or other immunosuppressive agents
• Known autoimmune disorder (exception: type 1 diabetes)
• Active infectious disease requiring antibiotic or anti-viral agents

Sponsors & Collaborators

• Canadian Medical and Surgical Knowledge Translation Research Group: lead

Study Sites (3)

Centrum Services Newmarket

Newmarket, Ontario, L3Y 2N1, Canada

Location

Diagnostic Assessment Centre

Scarborough Village, Ontario, M1S 4N6, Canada

Location

Langstaff Medical Centre

Woodbridge, Ontario, L4L 1A6, Canada

Location

Related Publications (18)

• Vassalli G. Aldehyde Dehydrogenases: Not Just Markers, but Functional Regulators of Stem Cells. Stem Cells Int. 2019 Jan 13;2019:3904645. doi: 10.1155/2019/3904645. eCollection 2019.

  PMID: 30733805 BACKGROUND

• Bajuk Studen K, Pfeifer M. Cardiometabolic risk in polycystic ovary syndrome. Endocr Connect. 2018 Jul;7(7):R238-R251. doi: 10.1530/EC-18-0129. Epub 2018 May 29.

  PMID: 29844207 BACKGROUND

• Rudnicka E, Suchta K, Grymowicz M, Calik-Ksepka A, Smolarczyk K, Duszewska AM, Smolarczyk R, Meczekalski B. Chronic Low Grade Inflammation in Pathogenesis of PCOS. Int J Mol Sci. 2021 Apr 6;22(7):3789. doi: 10.3390/ijms22073789.

  PMID: 33917519 BACKGROUND

• Murri M, Luque-Ramirez M, Insenser M, Ojeda-Ojeda M, Escobar-Morreale HF. Circulating markers of oxidative stress and polycystic ovary syndrome (PCOS): a systematic review and meta-analysis. Hum Reprod Update. 2013 May-Jun;19(3):268-88. doi: 10.1093/humupd/dms059. Epub 2013 Jan 9.

  PMID: 23303572 BACKGROUND

• Terenzi DC, Al-Omran M, Quan A, Teoh H, Verma S, Hess DA. Circulating Pro-Vascular Progenitor Cell Depletion During Type 2 Diabetes: Translational Insights Into the Prevention of Ischemic Complications in Diabetes. JACC Basic Transl Sci. 2018 Nov 5;4(1):98-112. doi: 10.1016/j.jacbts.2018.10.005. eCollection 2019 Feb.

  PMID: 30847424 BACKGROUND

• Balber AE. Concise review: aldehyde dehydrogenase bright stem and progenitor cell populations from normal tissues: characteristics, activities, and emerging uses in regenerative medicine. Stem Cells. 2011 Apr;29(4):570-5. doi: 10.1002/stem.613.

  PMID: 21308868 BACKGROUND

• Qadura M, Terenzi DC, Verma S, Al-Omran M, Hess DA. Concise Review: Cell Therapy for Critical Limb Ischemia: An Integrated Review of Preclinical and Clinical Studies. Stem Cells. 2018 Feb;36(2):161-171. doi: 10.1002/stem.2751. Epub 2018 Jan 3.

  PMID: 29226477 BACKGROUND

• Putman DM, Cooper TT, Sherman SE, Seneviratne AK, Hewitt M, Bell GI, Hess DA. Expansion of Umbilical Cord Blood Aldehyde Dehydrogenase Expressing Cells Generates Myeloid Progenitor Cells that Stimulate Limb Revascularization. Stem Cells Transl Med. 2017 Jul;6(7):1607-1619. doi: 10.1002/sctm.16-0472. Epub 2017 Jun 15.

  PMID: 28618138 BACKGROUND

• Terenzi DC, Bakbak E, Trac JZ, Al-Omran M, Quan A, Teoh H, Verma S, Hess DA. Isolation and characterization of circulating pro-vascular progenitor cell subsets from human whole blood samples. STAR Protoc. 2021 Feb 1;2(1):100311. doi: 10.1016/j.xpro.2021.100311. eCollection 2021 Mar 19.

  PMID: 33554145 BACKGROUND

• Xiong YL, Liang XY, Yang X, Li Y, Wei LN. Low-grade chronic inflammation in the peripheral blood and ovaries of women with polycystic ovarian syndrome. Eur J Obstet Gynecol Reprod Biol. 2011 Nov;159(1):148-50. doi: 10.1016/j.ejogrb.2011.07.012. Epub 2011 Sep 9.

  PMID: 21908093 BACKGROUND

• Mohammadi M. Oxidative Stress and Polycystic Ovary Syndrome: A Brief Review. Int J Prev Med. 2019 May 17;10:86. doi: 10.4103/ijpvm.IJPVM_576_17. eCollection 2019.

  PMID: 31198521 BACKGROUND

• Capoccia BJ, Robson DL, Levac KD, Maxwell DJ, Hohm SA, Neelamkavil MJ, Bell GI, Xenocostas A, Link DC, Piwnica-Worms D, Nolta JA, Hess DA. Revascularization of ischemic limbs after transplantation of human bone marrow cells with high aldehyde dehydrogenase activity. Blood. 2009 May 21;113(21):5340-51. doi: 10.1182/blood-2008-04-154567. Epub 2009 Mar 26.

  PMID: 19324906 BACKGROUND

• Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004 Jan;19(1):41-7. doi: 10.1093/humrep/deh098.

  PMID: 14688154 BACKGROUND

• Hess DA, Wirthlin L, Craft TP, Herrbrich PE, Hohm SA, Lahey R, Eades WC, Creer MH, Nolta JA. Selection based on CD133 and high aldehyde dehydrogenase activity isolates long-term reconstituting human hematopoietic stem cells. Blood. 2006 Mar 1;107(5):2162-9. doi: 10.1182/blood-2005-06-2284. Epub 2005 Nov 3.

  PMID: 16269619 BACKGROUND

• Hess DA, Terenzi DC, Trac JZ, Quan A, Mason T, Al-Omran M, Bhatt DL, Dhingra N, Rotstein OD, Leiter LA, Zinman B, Sabongui S, Yan AT, Teoh H, Mazer CD, Connelly KA, Verma S. SGLT2 Inhibition with Empagliflozin Increases Circulating Provascular Progenitor Cells in People with Type 2 Diabetes Mellitus. Cell Metab. 2019 Oct 1;30(4):609-613. doi: 10.1016/j.cmet.2019.08.015. Epub 2019 Aug 30.

  PMID: 31477497 BACKGROUND

• Aboeldalyl S, James C, Seyam E, Ibrahim EM, Shawki HE, Amer S. The Role of Chronic Inflammation in Polycystic Ovarian Syndrome-A Systematic Review and Meta-Analysis. Int J Mol Sci. 2021 Mar 8;22(5):2734. doi: 10.3390/ijms22052734.

  PMID: 33800490 BACKGROUND

• Putman DM, Liu KY, Broughton HC, Bell GI, Hess DA. Umbilical cord blood-derived aldehyde dehydrogenase-expressing progenitor cells promote recovery from acute ischemic injury. Stem Cells. 2012 Oct;30(10):2248-60. doi: 10.1002/stem.1206.

  PMID: 22899443 BACKGROUND

• Terenzi DC, Trac JZ, Teoh H, Gerstein HC, Bhatt DL, Al-Omran M, Verma S, Hess DA. Vascular Regenerative Cell Exhaustion in Diabetes: Translational Opportunities to Mitigate Cardiometabolic Risk. Trends Mol Med. 2019 Jul;25(7):640-655. doi: 10.1016/j.molmed.2019.03.006. Epub 2019 Apr 30.

  PMID: 31053416 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum samples to be retained for 5 years

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Insulin Resistance; Chronic Disease

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Subodh Verma, MD, PhD

  University of Toronto

  PRINCIPAL INVESTIGATOR

• David A Hess, PhD

  University of Western Ontario, Canada

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Irene Firoz, MB BCh BAO

CONTACT

6478194929; irene.firoz@mail.utoronto.ca

Aishwarya Krishnaraj, BScH

CONTACT

aishy.krishnaraj@mail.utoronto.ca

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2022
• First Posted: June 8, 2022
• Study Start: June 1, 2022
• Primary Completion: February 1, 2023
• Study Completion: April 1, 2023
• Last Updated: June 8, 2022

Record last verified: 2022-06

Locations

CA (3)