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COVID halting human subjects research and preliminary data from this proposal were used to submit an NIH grant. The NIH grant was funded and 3 other protocols were launched.
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Endometriosis is a disorder that occurs in women. With endometriosis, tissue that should be found in the womb is found in sites outside of the womb. This disorder impairs the function of the cells that line the body's blood vessels (endothelium). The endothelium helps to control blood flow in healthy vessels. Women with this disorder have an increased risk for high blood pressure and high cholesterol. They have a higher risk for cardiovascular disease, too. With this study, we will learn how endometriosis impairs the lining of blood vessels and increases the risk for disease.
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. We hypothesis that one factor mediating the elevated risk of cardiovascular disease in endometriosis is microRNA (miRNA) activation of LOX-1 receptor mechanisms.
Specific Aim 1. To test the hypothesis that LOX-1 receptor activation is increased leading to endothelial dysfunction in endometriosis.
Specific Aim 2. To test the hypothesis that decreased microRNAs (i.e. let7-a, let7-b, let7-g, MiR98, Mi590-p) are driving increased LOX-1 receptor expression and function in endometriosis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Atorvastatin | Experimental | Oral atorvastatin (Lipitor) therapy (10mg/day) for seven days. Atorvastatin acts as a systemic LOX inhibitor. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Atorvastatin | Drug | Simvastation acts as a systemic LOX inhibitor. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Nitric Oxide Dependent Vasodilation in the Skin | area under the curve of laser Doppler flux/mean arterial pressure * log acetylcholine (mol/L) | before and after intervention (7 days) |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Pennsylvania State University | University Park | Pennsylvania | 16801 | United States |
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6 enrolled
All endometriosis patients had a confirmed diagnosis prior to enrollment via laparoscopy.
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| ID | Title | Description |
|---|---|---|
| FG000 | Atorvastatin | Oral atorvastatin (Lipitor) therapy (10mg/day) for seven days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Atorvastatin | Oral atorvastatin (Lipitor) therapy (10mg/day) for seven days. Atorvastatin acts as a systemic LOX inhibitor. Atorvastatin: Simvastation acts as a systemic LOX inhibitor. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Nitric Oxide Dependent Vasodilation in the Skin | area under the curve of laser Doppler flux/mean arterial pressure * log acetylcholine (mol/L) | A subset (n = 6) of endometriosis patients participated in a seven-day oral atorvastatin (Lipitor®) therapy (10 mg/day). These subjects returned to the laboratory on day 7, having taken the final dose that morning. | Posted | Mean | Standard Error | flux/MAP*logAch(mol/L) | before and after intervention (7 days) |
|
2 weeks
other
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Atorvastatin | Oral atorvastatin (Lipitor) therapy (10mg/day) for seven days. Atorvastatin acts as a systemic LOX inhibitor. Atorvastatin: Simvastation acts as a systemic LOX inhibitor. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Lacy M. Alexander, Ph.D. | Penn State University | 8148671781 | lma191@psu.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 16, 2022 | Nov 27, 2023 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jan 28, 2021 | Nov 27, 2023 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D004715 | Endometriosis |
| ID | Term |
|---|---|
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
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| ID | Term |
|---|---|
| D000069059 | Atorvastatin |
| ID | Term |
|---|---|
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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Only women with endometriosis will complete this study. Once consented and screened, each subject is asked to take Atorvastatin (Lipitor, 10mg/day) for seven days. Participants will undergo experimental testing before and after the seven day intervention.
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| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Units |
|---|
| Counts |
|---|
| Participants |
|
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| 0 |
| 6 |
| 0 |
| 6 |
| 0 |
| 6 |
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| D000091662 | Genital Diseases |
| D006538 |
| Heptanoic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |