Insulin Resistance and Testosterone in Women - Full Text View

Sponsor:	University of Pennsylvania
Collaborators:	National Institute on Aging (NIA) The John A. Hartford Foundation National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) University of Pennsylvania Diabetes and Endocrinology Research Center (DERC) TAP Pharmaceutical Products Inc.
Information provided by:	University of Pennsylvania
ClinicalTrials.gov Identifier:	NCT00123110

Purpose

The purpose of this research study is to determine if a relationship between insulin resistance (IR) and testosterone (T) exists in women who have already gone through menopause.

Condition	Intervention	Phase
Insulin Resistance Postmenopause	Drug: metformin Drug: leuprolide acetate Drug: placebo pill Drug: placebo injection	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Insulin Resistance and Testosterone in Non-Diabetic Postmenopausal Women

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Medicines

Drug Information available for: Testosterone Propionate Methyltestosterone Testosterone Insulin Insulin beef Leuprolide Leuprolide acetate Oxymesterone Testosterone enanthate Metformin Metformin hydrochloride Testosterone undecanoate

U.S. FDA Resources

Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:

Free testosterone [ Time Frame: baseline, 4, 8, and 12 weeks ] [ Designated as safety issue: No ]
Insulin resistance [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Luteinizing hormone (LH), follicle stimulating hormone (FSH), sex hormone binding globulin (SHBG), estradiol, total testosterone [ Time Frame: baseline, 4, 8, and 12 weeks ] [ Designated as safety issue: No ]
Homeostasis model assessment index of insulin resistance (HOMA-IR) [ Time Frame: baseline 4, 8, and 12 weeks ] [ Designated as safety issue: No ]
Lipid profile including high-density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides (TG), total cholesterol [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
Systolic (SBP) and diastolic (DBP) blood pressure [ Time Frame: baseline, 4, 8, and 12 weeks ] [ Designated as safety issue: No ]
Free T and IR in women in whom Metabolic Syndrome (MetSyn, as defined by updated NCEP ATP III criteria) is present vs. those in whom MetSyn is absent [ Time Frame: baseline, 4, 8, and 12 weeks ] [ Designated as safety issue: No ]
Dehydroepiandrosterone sulfate (DHEA-S) [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
Surrogate measures of adiposity including body mass index (BMI), waist-to-hip ratio (WHR), and waist circumference [ Time Frame: baseline, 4, 8, and 12 weeks ] [ Designated as safety issue: No ]

Enrollment:	36
Study Start Date:	July 2005
Study Completion Date:	June 2008
Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 metformin plus placebo injection	Drug: metformin Initiated on 500 mg daily and titrated up to 1000 mg twice a day during the first four weeks, remaining at that dose until 12 weeks Other Name: Glucophage Drug: placebo injection matching injection every 4 weeks (e.g. baseline, 4, and 8 weeks)
Experimental: 2 leuprolide plus placebo pill	Drug: leuprolide acetate 3.75 mg injection every 4 weeks (e.g. at baseline, 4, and 8 weeks) Other Name: Lupron Drug: placebo pill matching pill twice a day for 12 weeks
Placebo Comparator: 3 placebo pill plus placebo injection	Drug: placebo pill matching pill twice a day for 12 weeks Drug: placebo injection matching injection every 4 weeks (e.g. baseline, 4, and 8 weeks)

Detailed Description:

This study tests the central hypothesis that insulin resistance (IR) increases androgen (male sex hormone) production in postmenopausal women. Participation will include five visits, each lasting on average 2.5 hours, over a period of 13-20 weeks.

At the screening visit, the participant's medical history, current use of medications and dietary supplements, and social habits will be recorded. This information will be reviewed on each subsequent visit; participants are asked to maintain their current diet and physical activity level throughout the study.

A brief physical exam will be performed, and blood will be drawn.

At the 2nd (baseline) visit, patients will undergo a euglycemic-hyperinsulinemic clamp (a procedure to measure insulin sensitivity by continuous intravenous infusion of insulin, and variable infusion of glucose). Blood samples will be drawn throughout the procedure. At completion, the insulin infusion will be stopped, participants will be fed, and the glucose infusion continued for at least 15 minutes to ensure stability of the blood glucose concentration. After the procedure, participants will be randomized to receive either metformin plus leuprolide placebo, leuprolide plus metformin placebo, or metformin placebo plus leuprolide placebo. The leuprolide or leuprolide placebo will be administered as an injection by a nurse. The metformin or metformin placebo will be dispensed to the participant in the form of pills, with instructions for titrating the dose. Participants will be contacted by telephone once weekly during the titration period to assess drug tolerability and adverse events (AEs). Participants will be maintained at their maximum tolerated dose for the duration of the study intervention period.

Participants will return every 4 weeks for follow-up. Blood will be drawn, the nurse will administer the leuprolide or leuprolide placebo injection, and metformin or metformin placebo will be dispensed. At the final visit (week 12), participants will undergo a brief physical exam, and will then undergo a final euglycemic-hyperinsulinemic clamp.

Eligibility

Ages Eligible for Study:	50 Years to 79 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Postmenopausal women aged 50-79 years with absence of menses for 12 months; for women 50-54 years, FSH>30 mIU/mL to confirm postmenopausal status
At least one intact ovary
Free testosterone and fasting insulin levels within required study parameters
Willing to comply with all study-related procedures
Capable of giving informed consent

Exclusion Criteria:

History of cancer requiring treatment within the past 5 years (exceptions may be made by investigator)
Hospitalization for treatment of vascular disease in the past 6 months
Uncontrolled hypertension
Hospitalization for chronic obstructive pulmonary disease or asthma in the past 3 months
Use of continuous oxygen at home
Surgery in the last 30 days
Positive for HIV
Abnormal blood tests (hemoglobin, fasting triglycerides, fasting glucose, creatinine, liver function)
History of diabetes mellitus or use of any anti-hyperglycemic medication in the past 3 months
Disease associated with disordered glucose metabolism (Cushing's disease, acromegaly, pheochromocytoma not surgically cured, chronic pancreatitis)
History of chronic renal insufficiency
Intravenous (IV) contrast studies with iodinated materials planned for the 12 week intervention period that cannot be postponed according to the participant's primary care provider
Acute or chronic metabolic acidosis
History of liver disease
Congestive heart failure
History of androgen-secreting tumors
Hormone replacement therapy or antiandrogen use in past 6 months
Use of DHEA or other androgen-containing products in past 6 months
Corticosteroid use, other than topical, ophthalmic, intraarticular, and inhaled preparations, in past 3 months
Undiagnosed current vaginal bleeding
Excessive alcohol intake, either acute or chronic; current illicit substance abuse
Participation in an investigational drug study within 6 weeks prior to screening visit
Serious or unstable medical or psychological conditions that, in the opinion of the investigator, would compromise the patient's safety or successful participation in the study

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00123110

Locations

United States, Pennsylvania
University of Pennsylvania Clinical and Translational Research Center
Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

University of Pennsylvania

National Institute on Aging (NIA)

The John A. Hartford Foundation

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

University of Pennsylvania Diabetes and Endocrinology Research Center (DERC)

TAP Pharmaceutical Products Inc.

Investigators

Principal Investigator:

Anne R. Cappola, MD, ScM

University of Pennsylvania

More Information

Publications:

Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA. 2002 Jan 16;287(3):356-9.

Golden SH, Ding J, Szklo M, Schmidt MI, Duncan BB, Dobs A. Glucose and insulin components of the metabolic syndrome are associated with hyperandrogenism in postmenopausal women: the atherosclerosis risk in communities study. Am J Epidemiol. 2004 Sep 15;160(6):540-8.

Larsson H, Ahren B. Androgen activity as a risk factor for impaired glucose tolerance in postmenopausal women. Diabetes Care. 1996 Dec;19(12):1399-403.

Oh JY, Barrett-Connor E, Wedick NM, Wingard DL; Rancho Bernardo Study. Endogenous sex hormones and the development of type 2 diabetes in older men and women: the Rancho Bernardo study. Diabetes Care. 2002 Jan;25(1):55-60.

Responsible Party:	Anne R. Cappola, MD, ScM, University of Pennsylvania School of Medicine
ClinicalTrials.gov Identifier:	NCT00123110 History of Changes
Other Study ID Numbers:	AG0031, K23AG019161, K23AG1916101A1, 5P30DK019525
Study First Received:	July 19, 2005
Last Updated:	March 9, 2010
Health Authority:	United States: Federal Government

Additional relevant MeSH terms:

Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Testosterone
Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Methyltestosterone
Leuprolide
Metformin
Androgens

Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anabolic Agents
Hypoglycemic Agents
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents

ClinicalTrials.gov processed this record on February 12, 2012