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Trial record 67 of 87 for:    NIDDK endocrine and diabetes | Recruiting, Not yet recruiting, Available Studies

Treating Inflammation in Polycystic Ovary Syndrome to Ameliorate Ovarian Dysfunction (TIN-PCOS-AOD)

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ClinicalTrials.gov Identifier: NCT03229408
Recruitment Status : Recruiting
First Posted : July 25, 2017
Last Update Posted : January 21, 2019
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Frank Gonzalez, University of Illinois at Chicago

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Polycystic Ovary Syndrome Drug: Salsalate Other: Placebo Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Treating Inflammation in Polycystic Ovary Syndrome to Ameliorate Ovarian Dysfunction
Actual Study Start Date : December 1, 2018
Estimated Primary Completion Date : July 31, 2022
Estimated Study Completion Date : July 31, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Salsalate-Treated Lean PCOS without IR
n=15
Drug: Salsalate
Lean PCOS Arms: Salsalate 1.5 gm PO bid; Obese PCOS Arm: Salsalate 2.0 gm PO bid
Other Names:
  • Disalcid®
  • Salsitab®
  • Amigesic®

Placebo Comparator: Placebo-Treated Lean PCOS without IR
n=15
Other: Placebo
Appears identical to experimental drug

Experimental: Salsalate-Treated Lean PCOS with IR
n=15
Drug: Salsalate
Lean PCOS Arms: Salsalate 1.5 gm PO bid; Obese PCOS Arm: Salsalate 2.0 gm PO bid
Other Names:
  • Disalcid®
  • Salsitab®
  • Amigesic®

Placebo Comparator: Placebo-Treated Lean PCOS with IR
n=15
Other: Placebo
Appears identical to experimental drug

Experimental: Salsalate-Treated Obese PCOS
n=15
Drug: Salsalate
Lean PCOS Arms: Salsalate 1.5 gm PO bid; Obese PCOS Arm: Salsalate 2.0 gm PO bid
Other Names:
  • Disalcid®
  • Salsitab®
  • Amigesic®

Placebo Comparator: Placebo-Treated Obese PCOS
n=15
Other: Placebo
Appears identical to experimental drug




Primary Outcome Measures :
  1. Aim 1: Area under the curve (AUC) for circulating testosterone from serial measurements during HCG stimulation test [ Time Frame: Change from pre-treatment baseline after 12 weeks of salsalate administration ]
    Serum ovarian androgen measurement

  2. Aim 2: Maximum lipid-stimulated mononuclear cell nuclear factor ĸB activation during cream challenge test [ Time Frame: Change from pre-treatment baseline after 12 weeks of salsalate administration ]
    Transcription factor that is the cardinal signal of inflammation


Secondary Outcome Measures :
  1. Aim1: Fractional glucose disappearance / insulin concentration unit during insulin-modified frequently-sampled intravenous tolerance test adjusted for hepatic and peripheral insulin clearance [ Time Frame: Change from pre-treatment baseline after 12 weeks of salsalate administration ]
    Peripheral insulin sensitivity measurement



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Polycystic ovary syndrome is a female endocrine disorder.
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • Hyperprolactinemia.
  • Uncontrolled thyroid disease.
  • 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.
  • Known or suspected pregnancy.
  • 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.
  • Acute or chronic inflammatory illnesses (e.g. upper respiratory infection, asthma, rheumatoid arthritis or systemic lupus erythematosus).
  • 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.
  • Regular smoking defined as more than 2 cigarettes a month, or any smoking within 30 days of beginning the study.
  • 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.
  • 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03229408


Contacts
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Contact: Frank González, M.D. (312) 413-1984 frgz12@uic.edu
Contact: Laurie Quinn, Ph.D. (312) 996-7906 lquinn1@uic.edu

Locations
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United States, Illinois
Frank González Recruiting
Chicago, Illinois, United States, 60612
Contact: Frank González, M.D.    312-413-1984 ext 3124131984    frgz12@uic.edu   
Contact: Frank González, M.D.    3124131984 ext 3124131984    frgz12@uic.edu   
Sponsors and Collaborators
University of Illinois at Chicago
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
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Principal Investigator: Frank González, M.D. University of Illinois at Chicago

Additional Information:
Publications:
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Responsible Party: Frank Gonzalez, Director, Laboratory for Reproductive Endocrine and Inflammation Research, University of Illinois at Chicago
ClinicalTrials.gov Identifier: NCT03229408     History of Changes
Other Study ID Numbers: UIC-PCOS-0617
R01DK107605-01 ( U.S. NIH Grant/Contract )
First Posted: July 25, 2017    Key Record Dates
Last Update Posted: January 21, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Frank Gonzalez, University of Illinois at Chicago:
Inflammation
Hyperandrogenism
Anovulation
Insulin Resistance
Additional relevant MeSH terms:
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Endocrine System Diseases
Polycystic Ovary Syndrome
Syndrome
Inflammation
Disease
Pathologic Processes
Ovarian Cysts
Cysts
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Salicylsalicylic acid
Sodium Salicylate
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action