Clinical trial NCT05410834: Pro-vascular Regenerative Cell Exhaustion in Women With Polycystic Ovarian Syndrome
Official title: The Characterization of Pro-vascular Regenerative Cell Exhaustion in Women With Polycystic Ovarian Syndrome
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Polycystic Ovary Syndrome
Keywords: Polycystic ovarian syndrome
Progenitor cells
Women's Health
Insulin resistance
Chronic disease
Lead sponsor: Canadian Medical and Surgical Knowledge Translation Research Group
Sponsor class: OTHER
First posted: 2022-06-08
Enrollment: 30
Sex: FEMALE
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
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.

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Frequency of circulating ALDHhiSSChi granulocytes
timeFrame: Baseline
Secondary outcomes:
measure: Number of circulating ALDHhiSSCmid monocytes
timeFrame: Baseline
measure: Number of circulating ALDHhiSSClo primitive progenitor cells
timeFrame: Baseline
Other outcomes:
Locations:
city: Newmarket
country: Canada
facility: Centrum Services Newmarket
state: Ontario
city: Scarborough
country: Canada
facility: Diagnostic Assessment Centre
state: Ontario
city: Woodbridge
country: Canada
facility: Langstaff Medical Centre
state: Ontario
Study officials:
affiliation: University of Toronto
name: Subodh Verma, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Western Ontario, Canada
name: David A Hess, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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