Trial record 2 of 5 for:    11790215 [PUBMED-IDS]

Insulin Resistance and Testosterone in Women

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00123110
Recruitment Status : Completed
First Posted : July 22, 2005
Last Update Posted : March 11, 2010
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

Brief Summary:
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 or disease Intervention/treatment Phase
Insulin Resistance Postmenopause Drug: metformin Drug: leuprolide acetate Drug: placebo pill Drug: placebo injection Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Insulin Resistance and Testosterone in Non-Diabetic Postmenopausal Women
Study Start Date : July 2005
Actual Primary Completion Date : June 2008
Actual Study Completion Date : June 2008

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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)

Primary Outcome Measures :
  1. Free testosterone [ Time Frame: baseline, 4, 8, and 12 weeks ]
  2. Insulin resistance [ Time Frame: baseline and 12 weeks ]

Secondary Outcome Measures :
  1. Luteinizing hormone (LH), follicle stimulating hormone (FSH), sex hormone binding globulin (SHBG), estradiol, total testosterone [ Time Frame: baseline, 4, 8, and 12 weeks ]
  2. Homeostasis model assessment index of insulin resistance (HOMA-IR) [ Time Frame: baseline 4, 8, and 12 weeks ]
  3. Lipid profile including high-density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides (TG), total cholesterol [ Time Frame: baseline and 12 weeks ]
  4. Systolic (SBP) and diastolic (DBP) blood pressure [ Time Frame: baseline, 4, 8, and 12 weeks ]
  5. 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 ]
  6. Dehydroepiandrosterone sulfate (DHEA-S) [ Time Frame: baseline and 12 weeks ]
  7. 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 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years to 79 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes

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

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 identifier (NCT number): NCT00123110

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.
Principal Investigator: Anne R. Cappola, MD, ScM University of Pennsylvania

Responsible Party: Anne R. Cappola, MD, ScM, University of Pennsylvania School of Medicine Identifier: NCT00123110     History of Changes
Other Study ID Numbers: AG0031
K23AG019161 ( U.S. NIH Grant/Contract )
5P30DK019525 ( U.S. NIH Grant/Contract )
First Posted: July 22, 2005    Key Record Dates
Last Update Posted: March 11, 2010
Last Verified: March 2010

Additional relevant MeSH terms:
Insulin Resistance
Glucose Metabolism Disorders
Metabolic Diseases
Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Hypoglycemic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Anabolic Agents
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents