Mechanisms and Interventions Addressing Accelerated Cardiovascular Disease Risk in Endometriosis
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Biopsy LOX-1 protein expression
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Single (Investigator)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Salsalate
3000 mg/day salsalate (1500 mg twice daily) for 5 days
干预措施: Salsalate Pill (Drug)
Placebo
1 capsule contain microcrystalline cellulose filler (twice daily) for 5 days
干预措施: Placebo (Drug)
结局指标
主要结局
Biopsy LOX-1 protein expression
时间窗: 5 days after treatment
Bio-Rad DC assay, western blot technique used for LOX-1 protein receptor expression
cutaneous vascular conductance
时间窗: 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
时间窗: 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
时间窗: 5 days after treatment
Peripheral Blood Mononuclear Cell Isolation, LOX-1 expression quantified using real time pCR
次要结局
- sera reproductive hormone analysis(5 days after treatment)
- sera cytokine expression analysis(5 days after treatment)
- skin biopsy biochemical analysis(5 days after treatment)
研究者
Lacy Alexander
Professor of Kinesiology
Penn State University