Cortisol Regulation in Polycystic Ovary Syndrome (PCOS) - Full Text View

Sponsor:	Oregon Health and Science University
Information provided by:	Oregon Health and Science University
ClinicalTrials.gov Identifier:	NCT00694759

Purpose

The purpose of this study is to determine if insulin resistance (how well the body uses insulin and clears sugar) can affect cortisol levels in normal healthy women and women with polycystic ovary syndrome of all body weights.

Condition	Intervention
Polycystic Ovary Syndrome	Drug: pioglitazone Drug: metformin Drug: placebo

Study Type:	Interventional
Study Design:	Basic Science, Randomized, Open Label, Placebo Control, Parallel Assignment
Official Title:	Cortisol Regulation in Polycystic Ovary Syndrome

Resource links provided by NLM:

Drug Information available for: Hydrocortisone acetate Hydrocortisone Proctofoam-HC Hydrocortisone hemisuccinate Hydrocortamate Pioglitazone Pioglitazone hydrochloride Hydrocortisone 21-sodium succinate Hydrocortisone cypionate Metformin Metformin hydrochloride Cortisol succinate Cortisol 21-phosphate

U.S. FDA Resources

Further study details as provided by Oregon Health and Science University:

Primary Outcome Measures:

The comparison of body surface area adjusted cortisol production rate (CPR/BSA) before and after insulin sensitizing therapy in women with PCOS. [ Time Frame: Before and after 6 months of insulin sensitizing therapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Comparisons of 24-hour values for adrenocorticotropic hormone , free-cortisol, and cortisol binding globulin. [ Time Frame: Before and after 6 months of insulin sensitizing therapy ] [ Designated as safety issue: No ]

Estimated Enrollment:	107
Study Start Date:	October 2006
Estimated Study Completion Date:	July 2011
Estimated Primary Completion Date:	June 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Active Comparator Pioglitazone will be given to women with PCOS. After one month and six months of therapy, measure (a) 24-hour CPR, ACTH, free cortisol, and CBG, (b) adipocyte, liver, and whole body HSD 1 activity, and (c) insulin sensitivity, visceral fat, and androgen levels.	Drug: pioglitazone 30 mg for 2 weeks, then 45 mg daily
B: Active Comparator Metformin will be given to women with PCOS. After one month and six months of therapy, measure (a) 24-hour CPR, ACTH, free cortisol, and CBG, (b) adipocyte, liver, and whole body HSD 1 activity, and (c) insulin sensitivity, visceral fat, and androgen levels.	Drug: metformin 500mg twice daily for 1 week, then 1000 mg twice daily
C: Placebo Comparator Placebo will be given to women with PCOS. After one month and six months of therapy, measure (a) 24-hour CPR, ACTH, free cortisol, and CBG, (b) adipocyte, liver, and whole body HSD 1 activity, and (c) insulin sensitivity, visceral fat, and androgen levels.	Drug: placebo capsule twice daily

Detailed Description:

PCOS is a common clinical problem affecting young women, characterized by oligomenorrhea and hyperandrogenism. Central obesity and insulin resistance are also prominent features of PCOS, and in addition are important risk factors for development of hypertension, hyperlipidemia and atherosclerotic heart disease. Previous studies have suggested that cortisol is dysregulated in PCOS, primarily through increased hypothalamic-pituitary-adrenal (HPA) axis activity and enhanced cortisol secretion. Increased adrenocorticotropic hormone (ACTH) secretion could also potentially lead to elevated adrenal androgen production in PCOS. Techniques used in previous studies have been inconsistent, however, and a link between increased HPA axis activity and the phenotypic changes in PCOS has not been clearly demonstrated. Cortisol is also produced from cortisone in peripheral adipose tissue by the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (HSD 1), suggesting another potential point of dysregulation that may contribute to central obesity and insulin resistance in PCOS. Further investigation of both central and peripheral regulation of cortisol is necessary to better understand the pathophysiology of PCOS.

Specific Aim 1: To perform a cross-sectional study of women with PCOS and normal controls matched for age and body mass index, and measure insulin sensitivity and visceral fat, as well as (a) 24-hour CPR, ACTH, free cortisol, and cortisol binding globulin (CBG), (b) adipocyte, liver, and whole body HSD 1 activity, and (c) androgen levels.

Specific Aim 2: To prospectively administer pioglitazone or metformin to women with PCOS in a placebo-controlled trial, and after one month and six months of therapy measure (a) 24-hour CPR, ACTH, free cortisol, and CBG, (b) adipocyte, liver, and whole body HSD 1 activity, and (c) insulin sensitivity, visceral fat, and androgen levels.

Eligibility

Ages Eligible for Study:	18 Years to 45 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria (Healthy controls):

Healthy
At lifetime maximal weight
Weight stable for at least 6 months prior to study entry
Willing to commit to not making significant changes to their diet or daily activities while enrolled.
Premenopausal
Have regular menstrual cycles
No evidence of hirsutism

Additional Inclusion Criteria (Subjects with PCOS):

Clinical findings of amenorrhea or oligomenorrhea dating from menarche
Clinical and/or biochemical evidence of hyperandrogenism
Exclusion of related disorders

Exclusion Criteria (Healthy controls):

Less than 18 years of age
Exercise > 30 minutes/day, 3 times a week
Smokers
Heavy alcohol drinkers (> 2 drinks/day)
Type 2 diabetes
Medical diagnoses including heart disease and cancer
Psychiatric illness (i.e.depression, psychosis, bipolar, schizophrenia)
Body weight > 136 kg
Pregnant
Endocrine diseases affecting body composition or androgen levels

Additional Exclusion Criteria (Subjects with PCOS):

Laboratory evidence of hyperprolactinemia, thyroid dysfunction, or 21-hydroxylase-deficient nonclassic CAH
Contraindication to pioglitazone (i.e. CHF, impaired liver function, anemia, depressed leukocyte counts, pulmonary disease, known sensitivity to thiazolidinediones.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00694759

Contacts

Contact: Bethany J Klopfenstein, MD	503-494-4020	klopfens@ohsu.edu
Contact: Jonathan Q Purnell	503-494-1056	purnellj@ohsu.edu

Locations

United States, Oregon
Oregon Health & Science University	Recruiting
Portland, Oregon, United States, 97239
Principal Investigator: Bethany J. Klopfenstein, MD

Sponsors and Collaborators

Oregon Health and Science University

Investigators

Principal Investigator:

Bethany J. Klopfenstein, MD

Oregon Health and Science University

More Information

No publications provided

Responsible Party:	Oregon Health & Science University ( Bethany Klopfenstein, MD )
Study ID Numbers:	OHSUIRB00002532
Study First Received:	June 6, 2008
Last Updated:	September 17, 2009
ClinicalTrials.gov Identifier:	NCT00694759 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Oregon Health and Science University:

Polycystic ovary syndrome
insulin
PCOS
cortisol regulation
regulation

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Disease
Hydrocortisone
Pioglitazone
Gonadal Disorders
Physiological Effects of Drugs
Metformin
Endocrine System Diseases
Ovarian Diseases
Cysts

Pharmacologic Actions
Adnexal Diseases
Genital Diseases, Female
Neoplasms
Hypoglycemic Agents
Pathologic Processes
Therapeutic Uses
Syndrome
Polycystic Ovary Syndrome
Ovarian Cysts

ClinicalTrials.gov processed this record on February 08, 2010