Simvastatin + Duavee for Endometriosis
(Endo2/SA3 Trial)
Recruiting in Palo Alto (17 mi)
Age: 18 - 65
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: Penn State University
Must not be taking: Cardiovascular medications
Disqualifiers: Diabetes, Hypertension, Pregnancy, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?Purpose: To determine the effects of SERM and simvastatin interventions on endothelial dysfunction in women with endometriosis.
Hypothesis: Treatment with the SERM (bazedoxifene + conjugated estrogen) or with simvastatin will decrease systemic inflammation and improve specific measures of cardiovascular function including endothelium-dependent vasodilation.
Will I have to stop taking my current medications?
The trial requires that you stop taking any medications that could affect blood vessel function, such as those for heart or blood sugar issues. If you're on such medications, you would need to stop them to participate.
What data supports the effectiveness of the drug Simvastatin + Duavee for treating endometriosis?
Research shows that bazedoxifene with conjugated estrogens, components of Duavee, can cause regression of endometriosis in animal studies and may be a potential treatment option. Simvastatin, another component, has been shown to reduce pain and inflammation in endometriosis patients.
12345Is the combination of Simvastatin and Duavee safe for humans?
Bazedoxifene with conjugated estrogens (Duavee) has been shown to be safe for treating menopausal symptoms and osteoporosis in postmenopausal women, with no significant stimulation of breast or uterine tissues. However, specific safety data for the combination of Simvastatin and Duavee for endometriosis is not available.
16789How is the drug Simvastatin + Duavee unique for treating endometriosis?
Simvastatin + Duavee is unique for treating endometriosis because it combines a cholesterol-lowering drug, simvastatin, which reduces inflammation, with bazedoxifene/conjugated estrogens, which can help shrink endometriotic lesions without the side effects of traditional hormone therapies. This combination offers a novel approach by targeting both inflammation and estrogen-driven growth of endometriosis.
12345Eligibility Criteria
This trial is for women aged 18-45 with a prior diagnosis of endometriosis confirmed by laparoscopy within the last 5 years. Participants must not use nicotine, have diabetes, high blood pressure, abnormal liver function, cardiovascular disease, skin conditions or allergies relevant to the study drugs, and cannot be pregnant or breastfeeding.Inclusion Criteria
I can take Tylenol for acute pain.
IUD contraceptive use (copper or levonogestrel) is allowed
I am a woman aged 18-45 with endometriosis diagnosed via laparoscopy within the last 10 years.
Exclusion Criteria
Known allergy to latex or investigative substances
I have or might have a metabolic or heart-related condition.
Pregnancy
+9 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Pre-treatment
Participants undergo baseline assessments including cutaneous microdialysis and flow mediated dilation experiments
30 days
1 visit (in-person)
Washout
A 60-day washout period to minimize potential carryover effects
60 days
Treatment
Participants receive either Simvastatin or SERM (bazedoxifene + conjugated estrogen) for 30 days
30 days
1 visit (in-person)
Follow-up
Participants are monitored for changes in reproductive hormones, microRNA activity, inflammation, LOX-1 activity, skin blood flow, and peripheral blood flow
30 days post-intervention
Participant Groups
The trial is testing whether simvastatin (10mg) and SERM (bazedoxifene + conjugated estrogens) can reduce inflammation and improve cardiovascular function in women with endometriosis. The focus is on how these treatments affect endothelium-dependent vasodilation—a marker of vascular health.
2Treatment groups
Experimental Treatment
Group I: bazedoxifene + conjugated estrogenExperimental Treatment1 Intervention
30 days of bazedoxifene + conjugated estrogen (0.45mg/20mg/day)
Group II: SimvastatinExperimental Treatment1 Intervention
30 days of Simvastatin (10mg/day)
Bazedoxifene/Estrogens,Conjugated is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Duavee for:
- Moderate to severe vasomotor symptoms associated with menopause
- Prevention of postmenopausal osteoporosis
🇪🇺 Approved in European Union as Duavive for:
- Treatment of oestrogen deficiency symptoms in postmenopausal women with an intact uterus with at least 12 months since last menses
- Prevention of osteoporosis in postmenopausal women at high risk of future fractures who are intolerant of, or contraindicated for, other medicinal products approved for the prevention of osteoporosis
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
The John B. Pierce LaboratoryNew Haven, CT
Loading ...
Who Is Running the Clinical Trial?
Penn State UniversityLead Sponsor
The John B. Pierce LaboratoryCollaborator
References
Bazedoxifene-Conjugated Estrogens for Treating Endometriosis. [2021]Endometriosis is a gynecologic disorder affecting 6-10% of reproductive-aged women. First-line therapies are progestin-based regimens; however, failure rates are high, often requiring alternative hormonal agents, each with unfavorable side effects. Bazedoxifene with conjugated estrogens is approved for treatment of menopausal symptoms, and use in animal studies has demonstrated regression of endometriotic lesions. As such, it represents a potential treatment option for endometriosis.
Effect of simvastatin on monocyte chemoattractant protein-1 expression in endometriosis patients: a randomized controlled trial. [2018]Simvastatin is a promising new drug for the treatment of endometriosis. It is a cholesterol-lowering drug that acts by inhibiting HMG-CoA reductase, resulting in a decrease in mevalonate, a precursor of cholesterol and monocyte chemoattractant protein-1 (MCP-1). This study investigated the effect of pre-operative oral simvastatin administration on MCP-1 gene expression and serum MCP-1 protein levels in patients with endometriosis.
Effects of simvastatin in prevention of pain recurrences after surgery for endometriosis. [2022]To compare efficacy of simvastatin with GnRHa (Decapeptyl 3.75 mg) on endometriosis-related pains following surgery for endometriosis.
Treatment with bazedoxifene, a selective estrogen receptor modulator, causes regression of endometriosis in a mouse model. [2021]Endometriosis is a common estrogen-dependent disorder. Medical treatments currently consist of progestins or GnRH agonists; however, neither is fully effective and both entail significant side effects. Selective estrogen receptor (ER) modulators (SERM) have tissue-selective actions, acting as an ER agonist in some tissues and ER antagonist in others. The SERM bazedoxifene (BZA) effectively antagonizes estrogen-induced uterine endometrial stimulation without countering estrogenic effects in bone or central nervous system. These properties make it an attractive candidate for use in the treatment of endometriosis. Experimental endometriosis was created in reproductive-age CD-1 mice. After 8 wk, 10 animals received i.p. injections of BZA (3 mg/kg·d) for 8 wk, whereas 10 received vehicle control. Mice were killed, and implant size was assessed. The mean size of the implants after treatment was 60 mm(2) in the control group and 21 mm(2) in the BZA treatment group (P = 0.03). Quantitative PCR and immunohistochemical analysis were used to determine the effect on endometrial gene expression. PCNA, ERα, and LIF mRNA and protein expression were significantly decreased in endometrium of the treated group. Caspase 3 mRNA expression was increased. Expression of PR and Hoxa10 were not significantly altered by treatment. There was no evidence of ovarian enlargement or cyst formation. Decreased PCNA and ER expression demonstrated that the regression of endometriosis likely involved decreased estrogen-mediated cell proliferation. BZA may be an effective novel agent for the treatment of endometriosis due to greater endometrial-specific estrogen antagonism compared with other SERM.
Bazedoxifene/conjugated estrogens in combination with leuprolide for the treatment of endometriosis. [2020]Bazedoxifene/conjugated estrogens can be used with leuprolide as effective add-back therapy in premenopausal women with endometriosis without unwanted stimulation of the breasts, CNS (Central Nervous System), or endometrium. Bazedoxifene/conjugated estrogens may be an effective progestin-free alternative to traditional add-back therapies.
Bazedoxifene for HRT? [2017]Duavive (Pfizer) is a modified-release formulation of conjugated oestrogens plus bazedoxifene acetate (a selective oestrogen receptor modulator). It is licensed for treatment of oestrogen deficiency symptoms in postmenopausal women with a uterus for whom treatment with progestogen-containing therapy is not appropriate.1,2 It was licensed by the European Medicines Agency (EMA) in 2014 and launched in the UK in July 2016.1,3 Here, we review the evidence on efficacy and safety of conjugated oestrogens/bazedoxifene and consider its place in the management of symptoms associated with the menopause.
Pharmacokinetics, Dose Proportionality, and Bioavailability of Bazedoxifene in Healthy Postmenopausal Women. [2018]Bazedoxifene is a selective estrogen receptor modulator that has estrogen agonist effects on bone and lipid metabolism while having neutral or estrogen antagonist effects on the breast and endometrium. The present report describes findings from 3 Phase I clinical studies that evaluated the single-dose pharmacokinetics (study 1; n = 84), multiple-dose pharmacokinetics (study 2; n = 23), and absolute bioavailability (study 3; n = 18) of bazedoxifene.
Effects of bazedoxifene/conjugated estrogens on endometrial safety and bone in postmenopausal women. [2013]Bazedoxifene/conjugated estrogens (BZA/CE) has demonstrated efficacy in improving vasomotor and vulvar/vaginal atrophy symptoms in postmenopausal women. This study evaluated the endometrial safety of BZA/CE and effects on bone mineral density (BMD) compared with CE/medroxyprogesterone acetate (MPA) and placebo.
Bazedoxifene: a new selective estrogen receptor modulator for the treatment of postmenopausal osteoporosis. [2012]Bazedoxifene acetate (WAY-140424; TSE-424) is an oral, nonsteroidal, indole-based selective estrogen receptor modulator (SERM) being developed for the prevention and treatment of osteoporosis. Preclinical studies on bazedoxifene have demonstrated estrogen agonist effects on the skeleton and lipid metabolism but not on breast and uterine endometrium. In combination with estrogen, bazedoxifene antagonizes the stimulatory action of estrogens on proliferation of breast cancer cells and endometrium. Phase III clinical studies have shown favorable effects on the skeleton without stimulation of endometrium and breast. Bazedoxifene prevents bone loss in postmenopausal women without osteoporosis and reduces vertebral fractures in women with postmenopausal osteoporosis. In women at high risk of fracture with multiple risk factors, bazedoxifene reduces nonvertebral fracture risk in post-hoc analysis. Bazedoxifene in combination with conjugated estrogens represents a new form of therapeutic agents for the treatment of postmenopausal symptoms and prevention of postmenopausal osteoporosis. Clinical trials with bazedoxifene/conjugated estrogens have shown beneficial effects on bone mineral density and bone turnover markers with improvement in vasomotor symptoms and little or no stimulation of breast and endometrium.