Role of Senescent Cells in Uterine Fibroid Pathogenesis (SOUL Study) (SOUL)

Role of Senescent Cells in Uterine Fibroid Pathogenesis

The investigators are evaluating the role of senescent cells in uterine fibroids.

Study Overview

• Status: Recruiting
• Conditions: Leiomyoma; Fibroid

Detailed Description

Uterine fibroids are prevalent tumors of uterus characterized by excessive fibrotic tissues. Using new cutting-edge computational methods, the investigators have found that small groups of senescent cells in fibroids work in concert with immune cells to produce soluble factors in fibroid tissues to create a feed-forward loop leading to fibrosis. This project seeks to unravel key cell-cell communication networks involving senescent and immune cells in fibroids to develop new treatments for uterine fibroids.

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: James Segars, MD; Phone Number: 410-614-2000; Email: jsegars2@jhmi.edu
• Study Contact Backup: Name: Bhuchitra Singh, MD, MPH, MBA; Phone Number: 410-614-2000; Email: bsingh10@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Johns Hopkins Hospital
      • Contact: Rachel Mitchel; Email: rmiche10@jhmi.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Women between the age of 18-55 years undergoing elective hysterectomy or myomectomy for uterine fibroids

Description

Inclusion Criteria:

• Subjects must be women above the age of ≥18 - ≤55 years.
• Women with suspected uterine fibroids.
• Subject must be or have been sexually active or have had a previous vaginal exam that used a speculum.
• Subject must be able to understand, read and speak English or Spanish and subsequently, be able to understand what she is consenting to in terms of procedures and use/disclosure of protected health information.

Exclusion Criteria:

• Unwilling to sign the consent form or complete questionnaire.
• Pregnancy.
• Cancer of the uterus

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Women with fibroids undergoing elective hysterectomy or myomectomy; Women between the age of 18-55 with fibroids undergoing elective hysterectomy or myomectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Develop an atlas to comprehensively quantify the rate of senescent cell (SnC) types in fibroid and myometrium tissue samples	Perform scRNASeq on human fibroids and control myometrium tissue and apply transfer learning algorithm for SnC identification and phenotyping to identify cell-cell communication patterns in fibroids versus control myometrial tissue using Domino to validate computationally predicted senescent cell types. The computationally predicted immune phenotypes will be validated with flow cytometry.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Validate the concentration senescence-associated secretory profile (SASP) in cell cultures of senescent cells in uterine fibroids	Quantify levels of transcripts and proteins in the fibroid senescence-associated secretory profile (SASP) using ELISA and western blotting techniques	5 years
Rate of inhibition of cellular proliferation and ECM deposition by senolytics and senomorphics in fibroids	Examine the in-vitro effects of senotherapeutcis using leiomyoma culture models and in mouse models. Measured by inhibition of proliferation, induction of apoptosis, inhibition ECM deposition, decrease in SnCs (senolytics) and senescence-associated secretory profile SASPs (senomorphics).	5 years

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institutes of Health (NIH)
• Investigators: Principal Investigator: James Segars, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2023
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: November 9, 2023
• First Submitted That Met QC Criteria: November 13, 2023
• First Posted (Actual): November 18, 2023

Study Record Updates

• Last Update Posted (Estimated): December 13, 2023
• Last Update Submitted That Met QC Criteria: December 6, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Fibroids; Leiomyomas; Senescent cells
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Connective Tissue Diseases; Neoplasms, Connective Tissue; Neoplasms, Muscle Tissue; Leiomyoma; Myofibroma
• Other Study ID Numbers: IRB00359032; 1R01HD111243 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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