NCT03229408Befejeződött2. fázis
Treating Inflammation in Polycystic Ovary Syndrome to Ameliorate Ovarian Dysfunction
Forrás: ClinicalTrials.gov · Utoljára frissítve: 2025. jún. 10.
Rövid összefoglaló (regiszter, angolul)
Polycystic Ovary Syndrome (PCOS) is characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovaries. Insulin resistance (IR) is a common feature of PCOS, and the resultant hyperinsulinemia is theorized to promote hyperandrogenism in the disorder. However, 30-50% of women with PCOS who are lean do not have insulin resistance. Women with PCOS also exhibit chronic low-grade inflammation. In PCOS, glucose ingestion activates nuclear factor ĸB (NFĸB), the cardinal signal of inflammation culminating in upregulation of the inflammation pathway within mononuclear cells (MNC). This phenomenon is independent of excess adiposity and is highly correlated with circulating androgens. In addition, in vitro exposure to proinflammatory stimuli is capable of directly stimulating ovarian theca cell androgen production. Nonacetylated salicylates suppress NFĸB activation and are well tolerated in humans. The proposed research is a randomized double-blind placebo-controlled study of 90 women with PCOS. Forty-five subjects with PCOS (15 lean without IR), 15 lean with IR and 15 obese) receiving salsalate, a nonacetylated salicylate, at an oral dose of 3-4 gm daily for 12 weeks will be compared with 45 age- and body-composition-matched control women with PCOS receiving placebo. The overarching hypothesis is that inflammation contributes to ovarian dysfunction, independent of excess adiposity or IR. The specific aims are, I: To examine the effect of salsalate administration on the ovarian capacity to secrete androgen and on insulin sensitivity in PCOS. II: To examine the effect of salsalate administration on the inflammatory response of mononuclear cells induced by lipid ingestion and glucose infusion in PCOS. The approach involves evaluation of ovarian androgen secretion in response to human chorionic gonadotropin (HCG) administration and insulin sensitivity during the euglycemic phase of a two-step pancreatic clamp along with ovulation monitoring before and after salsalate administration. The inflammatory response of MNC to lipid ingestion and the hyperglycemic phase of the two-step clamp will also be evaluated during treatment by measuring reactive oxygen species, the mRNA and protein content of inflammation markers, NFĸB activation and cytokine release in culture. The investigators expect that women with PCOS receiving salsalate will exhibit decreased ovarian androgen secretion and reduced inflammation regardless of adiposity or IR status. These results will be significant if they show a causal contribution of inflammation to ovarian dysfunction in PCOS, thus improving our understanding of the pathogenesis of PCOS, opening previously unexplored therapeutic avenues that are not necessarily dependent on improving IR, and guiding the design of future studies aimed at determining what interventions will optimally attenuate inflammation in PCOS to reduce medical disease and enhance fertility.
- Állapot (regiszter)
- Befejeződött
- Fázis (regiszter)
- 2. fázis
- Vizsgálattípus
- Beavatkozással járó
- Résztvevők száma
- 60 (tényleges)
- Első benyújtás
- 2017. júl. 15.
- Kezdés
- 2018. dec. 5.
- Elsődleges befejezés
- 2024. febr. 14.
- Fő szponzor
- University of Illinois Chicago
- NCT-szám
- NCT03229408
Mit vállalsz
- Vizsgálat típusa: Beavatkozással járó · 2. fázis
- Bevont résztvevők: 60
- 2018. dec. 5. és az elsődleges befejezés (2024. febr. 14.) között
- 1 helyszín, 1 országban
- Vizitek és vizsgálatok: kérdezd a vizsgálat csapatát, a regiszter nem sorolja fel őket
A(z) ClinicalTrials.gov regisztermezőiből összeállítva. A vizsgálat felépítését írja le.
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Korábbi kezelés
- Regular vigorous physical activity during previous 6 months.
- Use of any medications known to affect carbohydrate or sex hormone metabolism such as oral contraceptives, progestins, glucocorticoids or insulin sensitizing agents within 30 days of beginning the study.
Más betegség
- Uncontrolled thyroid disease.
- Acute or chronic inflammatory illnesses (e.g. upper respiratory infection, asthma, rheumatoid arthritis or systemic lupus erythematosus).
- History of any illness exacerbated by salicylate use (e.g. peptic ulcer hepatic or renal disease, anemia, thrombosis, coagulopathy, congestive heart failure, hypertension or gout).
- Allergy to salicylate or dairy products.
Laborértékek
- Evidence of Cushing's syndrome, nonclassic congenital adrenal hyperplasia or a hormone producing tumor based on physical findings and serum androgen levels on initial screening.
- Type 1 or type 2 diabetes mellitus defined as having a fasting glucose \>126 mg/dl and/or a 2-hour postprandial glucose \>200 mg/dl.
- Medication use interacting with salicylates such as anti-platelet drugs (e.g. cilostazol, clopidogrel), anticoagulants (e.g. enoxaparin, heparin, warfarin), corticosteroids (e.g., prednisone), certain diabetes drugs (e.g. sulfonylureas such as glyburide), certain anti-seizure drugs (e.g. phenytoin, valproic acid), cidofovir, cyclosporine, drugs for gout (e.g. probenecid, sulfinpyrazone), anti-hypertensives (e.g. angiotensin converting enzyme inhibitors such as captopril, angiotensin II receptor antagonists such as losartan, and beta blockers such as metoprolol), drugs that affect the acidity of urine (e.g. ammonium chloride, acetazolamide), lithium, methotrexate, oral bisphosphonates (e.g. alendronate), pemetrexed, selective serotonin reuptake inhibitor antidepressants (e.g. fluoxetine, sertraline), tenofovir, and diuretics (furosemide, hydrochlorothiazide, spironolactone).
Egyéb
- Hyperprolactinemia.
- Known or suspected pregnancy.
- Regular smoking defined as more than 2 cigarettes a month, or any smoking within 30 days of beginning the study.
Kiket keres a vizsgálat
- Diagnosis of PCOS based on the presence of hyperandrogenism (skin manifestations of androgen excess such as hirsutism, acne or temporal balding - or -elevation of at least one serum androgen \[i.e. total testosterone, free testosterone, androstenedione or dehydroepiandrosterone-sulphate\] using predetermined local laboratory cutoffs), oligo/amenorrhea and evidence of withdrawal bleeding after progestin administration.
- 18-40 years of age.
- Good health as evidenced by medical history, physical examination and gynecologic examination within 30 days prior to starting the study.
- Willingness to provide informed consent according to the guidelines of the University of Illinois at Chicago (UIC) Institutional Review Board (IRB).
- Willingness to use double-barrier contraception such as condoms and topical spermicide (foam, cream or gel), condom and diaphragm, diaphragm and topical spermicide or sponge with topical spermicide if sexually active. Use of a non-hormonal intrauterine device (IUD), or permanent sterilization of the subject or her partner (i.e. tubal ligation or vasectomy) is also acceptable in all instances.
Életkor a regiszterben: 18 év – 40 év · Nem: csak nők · Egészséges önkénteseket is fogad
Helyszínek (1)
Helyszínek a regiszter sorrendjében. Ha a profilodba mented a városodat, távolság szerint rendeződnek.
| Helyszín | Város | Ország | Helyszín állapota |
|---|---|---|---|
| Frank González Ennek a helyszínnek vagy a koordinátora? Erősítsd meg az állapotát | Chicago | Egyesült Államok | Ismeretlen állapot |
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