EndometriosisEarly Phase 1Endo3/SA2NCT05069740
Endometriosis and Microvascular Dysfunction: Role of Inflammation
A Early Phase 1 study testing Salsalate Pill in people with Endometriosis, run by Penn State University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Endometriosis
- What is being tested?
- Salsalate Pill
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jan 2022to 31 Dec 2026
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
The Pennsylvania State University
University Park, Pennsylvania, 16801
Lacy M Alexander, PhD, 814-867-1781, lma191@psu.edu
About this study
Official title: Mechanisms and Interventions Addressing Accelerated Cardiovascular Disease Risk in Endometriosis
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.
Read the detailed description
Endometriosis is an estrogen-dependent gynecological disorder associated with considerable chronic pelvic pain, pain during intercourse, and is a major cause of infertility. This disorder affects 6% - 10% of reproductive age women and can be as high as 35-50% in women experiencing pain or infertility. Endometriosis derives from the presence of endometrium-like tissue in sites outside the uterine cavity. While endometriosis is a local inflammatory syndrome, the inflammatory process is systemic.
Endometriosis is associated with higher risk of hypercholesterolemia and hypertension 8. Epidemiologic data demonstrate a clear association between endometriosis, reproductive risk factors, inflammation and cardiovascular (CV) risk.
Endometriosis a disease of inflammation and increased systemic inflammatory cytokine production, although the precise mechanisms by which localized lesion results in systemic inflammation are incompletely understood. Published data confirm an elevation of several inflammatory cytokines in the circulation of women with endometriosis. Alterations in circulating miRNAs specific to endometriosis are one mechanism causing immune dysfunction and subsequent increased cytokine expression in areas remote from the endometriotic lesions. This aberrant increase in systemic cytokine production is a highly plausible putative link to accelerated vascular dysfunction and atherosclerosis in women with endometriosis.
The circulating factors LDL and oxidized LDL are two of the 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 is a ubiquitously expressed scavenger receptor, stimulated by oxLDL, Ang II, and other inflammatory cytokines, and inhibited by estrogen. LOX-1 is the upstream signaling initiator of mechanisms including increased oxidant production, reduced nitric oxide (NO) metabolism, and impaired intracellular trafficking. Thus, LOX-1 signal transduction functionally results in pronounced endothelial dysfunction.
- Conditions
- Endometriosis
- Being tested
- Salsalate Pill, Placebo
- Keywords
- skin blood flow, inflammation, Lectin-like oxidized LDL receptor (LOX-1), intradermal microdialysis
- Medical subject headings
- Endometriosis, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Salsalate PillDrug
Salsalate acts as an NFkB inhibitor to reduce systemic inflammation
PlaceboDrug
Placebo for the salsalate intervention
| Study group | Role | What they receive |
|---|---|---|
| Salsalate | Experimental | 3000 mg/day salsalate (1500 mg twice daily) for 5 days Receives: Drug: Salsalate Pill |
| Placebo | Placebo comparator | 1 capsule contain microcrystalline cellulose filler (twice daily) for 5 days Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
cutaneous vascular conductance
doppler flowmetry used to measure cutaneous vascular conductance (cvc = red cell flux/mean arterial pressure) to assess microvascular endothelial function
Measured: 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
Measured: 5 days after treatment
Sera LOX-1 protein expression
Peripheral Blood Mononuclear Cell Isolation, LOX-1 expression quantified using real time pCR
Measured: 5 days after treatment
Biopsy LOX-1 protein expression
Bio-Rad DC assay, western blot technique used for LOX-1 protein receptor expression
Measured: 5 days after treatment
Secondary outcomes (3)
sera reproductive hormone analysis
analysis of plasma estradiol, progesterone, and sex hormone binding globulin determined through hormone assay
Measured: 5 days after treatment
sera cytokine expression analysis
expression of cytokines CRP, TNF-a, IL-1B, IL-6, IL-8 determined through multiplex assay
Measured: 5 days after treatment
skin biopsy biochemical analysis
the expression of estrogen receptor alpha and beta, the protein pVASP/VASP, and the enzyme peNOS/eNOS is determined using Bio-Rad DC assay, western blot technique
Measured: 5 days after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2021
- Study start1 Jan 2022
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EndometriosisStudies of the same condition, open and under way.
- More trials run by Penn State UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 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.
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Penn State University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lacy Alexander, Penn State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05069740
- Sponsor's protocol ID
- 18369
- Acronym
- Endo3/SA2
- Status last verified
- Jul 2026
- First submitted
- 10 Sep 2021
- Last updated
- 27 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms and Interventions Addressing Accelerated Cardiovascular Disease Risk in Endometriosis
- ClinicalTrials.gov ID
- NCT05069740
- Acronym / sponsor ID
- Endo3/SA2 / 18369
- Conditions
- Endometriosis
- Keywords
- skin blood flow, inflammation, Lectin-like oxidized LDL receptor (LOX-1), intradermal microdialysis
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Penn State UniversityUniversity, hospital or other
- Study start
- 1 Jan 2022 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 6 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Endometriosis is an estrogen-dependent gynecological disorder associated with considerable chronic pelvic pain, pain during intercourse, and is a major cause of infertility. This disorder affects 6% - 10% of reproductive age women and can be as high as 35-50% in women experiencing pain or infertility. Endometriosis derives from the presence of endometrium-like tissue in sites outside the uterine cavity. While endometriosis is a local inflammatory syndrome, the inflammatory process is systemic.
Endometriosis is associated with higher risk of hypercholesterolemia and hypertension 8. Epidemiologic data demonstrate a clear association between endometriosis, reproductive risk factors, inflammation and cardiovascular (CV) risk.
Endometriosis a disease of inflammation and increased systemic inflammatory cytokine production, although the precise mechanisms by which localized lesion results in systemic inflammation are incompletely understood. Published data confirm an elevation of several inflammatory cytokines in the circulation of women with endometriosis. Alterations in circulating miRNAs specific to endometriosis are one mechanism causing immune dysfunction and subsequent increased cytokine expression in areas remote from the endometriotic lesions. This aberrant increase in systemic cytokine production is a highly plausible putative link to accelerated vascular dysfunction and atherosclerosis in women with endometriosis.
The circulating factors LDL and oxidized LDL are two of the 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 is a ubiquitously expressed scavenger receptor, stimulated by oxLDL, Ang II, and other inflammatory cytokines, and inhibited by estrogen. LOX-1 is the upstream signaling initiator of mechanisms including increased oxidant production, reduced nitric oxide (NO) metabolism, and impaired intracellular trafficking. Thus, LOX-1 signal transduction functionally results in pronounced endothelial dysfunction.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (investigator)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Salsalate | Experimental | Drug: Salsalate Pill3000 mg/day salsalate (1500 mg twice daily) for 5 days |
| Placebo | Placebo comparator | Drug: Placebo1 capsule contain microcrystalline cellulose filler (twice daily) for 5 days |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Salsalate PillSalsalate acts as an NFkB inhibitor to reduce systemic inflammation | Drug | Salsalate |
| PlaceboPlacebo for the salsalate intervention | Drug | Placebo |
Primary outcome
cutaneous vascular conductance
Time frame: 5 days after treatment
doppler flowmetry used to measure cutaneous vascular conductance (cvc = red cell flux/mean arterial pressure) to assess microvascular endothelial function
brachial artery diameter and blood flow velocity
Time frame: 5 days after treatment
continuous ultrasound imaging measurements of brachial artery diameter and blood flow velocity to assess endothelial function
Sera LOX-1 protein expression
Time frame: 5 days after treatment
Peripheral Blood Mononuclear Cell Isolation, LOX-1 expression quantified using real time pCR
Biopsy LOX-1 protein expression
Time frame: 5 days after treatment
Bio-Rad DC assay, western blot technique used for LOX-1 protein receptor expression
3 secondary outcomes
sera reproductive hormone analysis
Time frame: 5 days after treatment
sera cytokine expression analysis
Time frame: 5 days after treatment
skin biopsy biochemical analysis
Time frame: 5 days after treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Salsalate Pill in people with Endometriosis, run by Penn State University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lacy M Alexander, Ph.D. (8148671781, lma191@psu.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
cutaneous vascular conductance (time frame: 5 days after treatment). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2026.