Endometriosis and Microvascular Dysfunction: Role of Inflammation

NCT05069740 | Recruiting Early Phase 1 FDA Drug

• 1 other identifier: 18369
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to better understand the underlying mechanisms associated with elevated cardiovascular disease risk in women with endometriosis, and to measure the effectiveness of emerging endometriosis treatments on outcomes specific to cardiovascular dysfunction. Epidemiologic data demonstrate a clear association between endometriosis, reproductive risk factors, inflammation and cardiovascular (CV) risk. Circulating factors, low-density lipoprotein (LDL) and oxidized LDL (oxLDL), are two of many biomarkers of cardiovascular and inflammatory disease of endometriosis. An important signaling mechanism through which circulating LDL and oxLDL act is the lectin-like oxidized LDL receptor (LOX-1). LOX-1 signal transduction functionally results in pronounced endothelial dysfunction, a hallmark of CV. The investigators hypothesis that one factor mediating the elevated risk of cardiovascular disease in endometriosis is systemic inflammation and activation of LOX-1 receptor mechanisms.

Conditions

Endometriosis

Keywords

skin blood flow; inflammation; Lectin-like oxidized LDL receptor (LOX-1); intradermal microdialysis

Outcome Measures

Primary Outcomes (4)

• cutaneous vascular conductance

  doppler flowmetry used to measure cutaneous vascular conductance (cvc = red cell flux/mean arterial pressure) to assess microvascular endothelial function

  5 days after treatment

• brachial artery diameter and blood flow velocity

  continuous ultrasound imaging measurements of brachial artery diameter and blood flow velocity to assess endothelial function

  5 days after treatment

• Sera LOX-1 protein expression

  Peripheral Blood Mononuclear Cell Isolation, LOX-1 expression quantified using real time pCR

  5 days after treatment

• Biopsy LOX-1 protein expression

  Bio-Rad DC assay, western blot technique used for LOX-1 protein receptor expression

  5 days after treatment

Secondary Outcomes (3)

• sera reproductive hormone analysis

  5 days after treatment

• sera cytokine expression analysis

  5 days after treatment

• skin biopsy biochemical analysis

  5 days after treatment

Study Arms (2)

Salsalate

EXPERIMENTAL

3000 mg/day salsalate (1500 mg twice daily) for 5 days

Drug: Salsalate Pill

Placebo

PLACEBO COMPARATOR

1 capsule contain microcrystalline cellulose filler (twice daily) for 5 days

Drug: Placebo

Interventions

Salsalate Pill DRUG

Salsalate acts as an NFkB inhibitor to reduce systemic inflammation

Salsalate

Placebo DRUG

Placebo for the salsalate intervention

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy women between the ages of 18 and 45 years (Controls), taking oral contraceptive or with regular menses every 26-34 days
• Women between the ages of 18 and 45 years with endometriosis (diagnosis by prior laparoscopy by subject's own physician \<5 years prior, and reported by the subject to the researchers)
• Tylenol if the subject has acute pain is allowed
• Contraceptive use is allowed

You may not qualify if:

• Use of nicotine-containing products (e.g. smoking, chewing tobacco, etc.)
• Diabetes (HbA1C 6.5%)
• BP\>140/90
• Taking pharmacotherapy that could alter peripheral vascular control (e.g. insulin sensitizing, cardiovascular medications)
• Pregnancy
• Breastfeeding
• Taking illicit and/or recreational drugs
• Abnormal liver function
• Rash, skin disease, disorders of pigmentation, known skin allergies
• Diagnosed or suspected metabolic or cardiovascular disease
• Persistent unexplained elevations of serum transaminases
• Known allergy to latex or investigative substances (including salsalate or simvastatin)
• History of gastrointestinal bleeding

Sponsors & Collaborators

• Penn State University: lead

Study Sites (1)

The Pennsylvania State University

University Park, Pennsylvania, 16801, United States

RECRUITING

MeSH Terms

Conditions

Endometriosis; Inflammation

Interventions

salicylsalicylic acid

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Lacy M Alexander, Ph.D.

CONTACT

8148671781; lma191@psu.edu

Susan Slimak, RN

CONTACT

814-863-8554; sks31@psu.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: These treatments/placebo are blinded to the investigators. The subjects, physician, and the nurse on staff knows which treatment the subject is taking if there are any questions or safety concerns.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Kinesiology

Model Details: This is a single blind placebo controled cross over study. Two groups of women complete this study: 1) healthy women between the ages of 18 and 45 years (Controls); 2) women between the ages of 18 and 45 years with endometriosis. Once consented and screening, each subject is randomized to either 5 days of salsalate or placebo. On day 5, each subject participates in a cutaneous microdialysis (MD) and flow mediated dilation (FMD) experiment. After a 2-week washout, the participant returns to repeat the study with the other oral drug (salsalate/placebo). These treatments are blinded to only the investigators. The participants and nurse on staff knows which treatment the subject is taking if there are any questions or safety concerns.

Study Record Dates

• First Submitted: September 10, 2021
• First Posted: October 6, 2021
• Study Start: January 1, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: July 27, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)