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

Polycystic Ovary Syndrome Clinical Trial

— PCOS-RCE  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05410834
• Other study ID #: Pro00063366
• Status: Not yet recruiting
• Start date: June 2022
• Est. completion date: April 2023

Study information

• Verified date: June 2022
• Source: Canadian Medical and Surgical Knowledge Translation Research Group
• Contact: Irene Firoz, MB BCh BAO
• Phone: 6478194929
• Email: irene.firoz[@]mail.utoronto.ca
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

Individuals with polycystic ovarian syndrome (PCOS) have been reported to be at higher risk of cardiovascular disease when compared to those without PCOS. While differential environmental exposures and genetic morphometries are believed to account in part for the difference, there is growing evidence that cardiometabolic risk factors can accelerate pro-vascular progenitor cell depletion and dysfunction. The cumulative effects that aberrant regenerative cell exhaustion (RCE) have on vessel repair accordingly increases the risk of atherothrombotic events.

PCOS-RCE is an observational, cross-sectional, two-arm study that will evaluate the progenitor cell profiles of peripheral blood samples from 30 individuals (15 with PCOS, 15 without PCOS). The working hypothesis is that individuals with PCOS have innately different progenitor cell profiles that can be further altered by their environment and genotype. The resultant differences in RCE capability will affect the balance between pro-inflammatory and vessel repair functions that, in turn, contribute to the contrasting cardiometabolic risks exhibited between the two study cohorts.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: April 2023
• Est. primary completion date: February 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 30 Years and older

Eligibility

Inclusion Criteria:

• Capable and willing to provide informed consent

• Females aged 30 and above

• Must meet criteria for one of the following two groups:

1. Documented diagnosis of PCOS OR

2. Normal and regular menstrual cycles with no known diagnosis of PCOS

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Polycystic Ovary Syndrome
• Syndrome

Locations

Country	Name	City	State
Canada	Centrum Services Newmarket	Newmarket	Ontario
Canada	Diagnostic Assessment Centre	Scarborough	Ontario
Canada	Langstaff Medical Centre	Woodbridge	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Canadian Medical and Surgical Knowledge Translation Research Group

Country where clinical trial is conducted

Canada, 

References & Publications (18)

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). pii: 2734. doi: 10.3390/ijms22052734. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. Epub 2005 Nov 3. — View Citation

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. Review. — View Citation

Murri M, Luque-Ramírez 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. Review. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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). pii: 3789. doi: 10.3390/ijms22073789. Review. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of circulating ALDHhiSSChi granulocytes	Difference in the frequency of circulating ALDHhi SSChi granulocytes between women with PCOS versus without PCOS	Baseline
Secondary	Number of circulating ALDHhiSSCmid monocytes	Difference in the number of circulating ALDHhi SSCmid monocytes with M1 vs M2 polarization between women with PCOS versus without PCOS	Baseline
Secondary	Number of circulating ALDHhiSSClo primitive progenitor cells	Difference in the number of circulating ALDHhi SSClo primitive progenitor cells in women with PCOS versus without PCOS	Baseline