PAI-1, tPA, TFPI and HEECs in Uterine Hemostasis

The Role of Plasminogen Activator Inhibitor-1 (PAI-1), Tissue Plasminogen Activator (tPA), Tissue Factor Pathway Inhibitor (TFPI), and Endometrial Endothelial Cells in Uterine Hemostasis in Humans

The purpose of the study is to learn more about the role of blood clotting factor proteins and cells in menstrual (period) bleeding. The investigators are hoping to identify differences in these proteins and cells in the menstrual blood of individuals with heavy periods compared to menstruating individuals who do not have heavy periods.

Study Overview

• Status: Recruiting
• Conditions: Menstrual Bleeding, Heavy
• Intervention / Treatment: Procedure: Sample Collection and Endometrial Biopsy

Detailed Description

The purpose of this study is to learn if human endometrial endothelial cells (HEECs) regulate human uterine hemostasis through the up and down-regulation of pro- and anti-coagulant factors in menstrual blood including PAI-1, factor XI (FXI)-PAI-1 complex, tPA, and TFPI.

This study will enroll participants with heavy menstrual bleeding (HMB) and participants without HMB. Coagulation factors will be measured in menstrual blood and mRNA for these factors will be quantified from cultured HEECS from endometrial biopsies and compared between groups.

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Women's Health Research Unit Department of Ob/Gyn; Phone Number: 503-494-3666; Email: whru@ohsu.edu

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • OHSU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Regularly menstruating participants between 18-45 years of age

Exclusion Criteria:

• Pregnancy within 3 months of enrollment
• Lactating at the time of enrollment
• Hormonal contraceptive use or use of the copper intrauterine device (IUD)
• Antifibrinolytic use
• Inherited or acquired bleeding disorder or anticoagulant use
• Known structural cause of HMB
• Inability to complete PBACs
• Unwilling to refrain from sexual intercourse for the two weeks prior to endometrial biopsy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Heavy Menstrual Bleeding; Participants with heavy menstrual bleeding will provide daily samples of menstrual blood for a single cycle and undergo a single endometrial biopsy for HEEC culture.	Procedure: Sample Collection and Endometrial Biopsy; Participants will provide daily samples of menstrual blood for a single cycle and undergo a single endometrial biopsy for HEEC culture.
Active Comparator: Regular Mensural Bleeding; Participants with normal menstrual bleeding will provide daily samples of menstrual blood for a single cycle and undergo a single endometrial biopsy for HEEC culture.	Procedure: Sample Collection and Endometrial Biopsy; Participants will provide daily samples of menstrual blood for a single cycle and undergo a single endometrial biopsy for HEEC culture.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total number of mRNA copies from HEEC culture of tPA	The total number of mRNA copies of tPA in HEEC cultures from enrollment to 60 days.	Enrollment to 60 days
Total number of mRNA copies from HEEC culture of PAI-1	The total number of mRNA copies of PAI-1 in HEEC cultures from enrollment to 60 days.	Enrollment to 60 days
Total number of mRNA copies from HEEC culture of TFPI	The total number of mRNA copies of TFPI in HEEC cultures from enrollment to 60 days.	Enrollment to 60 days
Change in the numerical score of Pictorial Blood Loss Assessment	The change in the Pictorial Blood Loss Assessment Charts (PBACs) from baseline to 60 days. Participants will be asked to tally the number of pads and tampons, the level of saturation of menstrual blood on the pads or tampons, and the number of clots. Scores greater than 100 are considered diagnostic of heavy menstrual bleeding.	Enrollment to 60 days

Collaborators and Investigators

• Sponsor: Oregon Health and Science University

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2023
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: May 8, 2023
• First Submitted That Met QC Criteria: May 8, 2023
• First Posted (Actual): May 17, 2023

Study Record Updates

• Last Update Posted (Actual): July 20, 2023
• Last Update Submitted That Met QC Criteria: July 18, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Uterine Diseases; Hemorrhage; Menstruation Disturbances; Uterine Hemorrhage; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Menorrhagia
• Other Study ID Numbers: OHSU IRB 23749

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No