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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.
 
ClinicalTrials.gov Identifier: NCT00123110
Recruitment Status : Completed
First Posted : July 22, 2005
Results First Posted : May 23, 2019
Last Update Posted : May 23, 2019
Sponsor:
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 (Responsible Party):
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 injection 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 35 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 : December 2011
Actual Study Completion Date : December 2011

Resource links provided by the National Library of Medicine

Drug Information available for: Metformin

Arm Intervention/treatment
Experimental: 1
metformin pill 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 injection plus placebo pill
Drug: leuprolide injection
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. Percent Change in Free Testosterone (T) [ Time Frame: Baseline to 12 weeks ]
    Percent change in free T by equilibrium dialysis between baseline and 12 weeks

  2. Change in Insulin Sensitivity [ Time Frame: baseline and 12 weeks ]
    Change in insulin sensitivity (mg/kg/min) calculated from hyperinsulinemic euglycemic clamp


Secondary Outcome Measures :
  1. Percent Change in Luteinizing Hormone (LH) From Baseline [ Time Frame: baseline and 12 weeks ]
  2. Percent Change in Homeostasis Model Assessment Index of Insulin Resistance (HOMA-IR) [ Time Frame: baseline and 12 weeks ]
    Insulin resistance calculated from homeostasis model assessment of insulin resistance (HOMA-IR) equation: fasting insulin x fasting glucose / 405. Higher values indicate more insulin resistance.

  3. Percent Change in Low Density Lipoprotein (LDL) [ Time Frame: baseline and 12 weeks ]
  4. Percent Change in Systolic Blood Pressure [ Time Frame: baseline and 12 weeks ]
  5. Free T and IR in Women in Whom Metabolic Syndrome is Present vs. Absent [ Time Frame: baseline and 12 weeks ]
  6. Dehydroepiandrosterone Sulfate (DHEA-S) [ Time Frame: baseline and 12 weeks ]
  7. Body Mass Index (BMI) [ Time Frame: baseline and 12 weeks ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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
Criteria

Inclusion Criteria:

  • Postmenopausal women aged 50-79 years with absence of menses for 12 months; for women 50-54 years, Follicle stimulating hormone>30 U/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 dehydroepiandosterone (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 ClinicalTrials.gov identifier (NCT number): NCT00123110


Locations
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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
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Principal Investigator: Anne R. Cappola, MD, ScM University of Pennsylvania
Publications:
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Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT00123110    
Other Study ID Numbers: AG0031
K23AG019161 ( U.S. NIH Grant/Contract )
K23AG1916101A1 ( Other Grant/Funding Number: NIA )
5P30DK019525 ( U.S. NIH Grant/Contract )
First Posted: July 22, 2005    Key Record Dates
Results First Posted: May 23, 2019
Last Update Posted: May 23, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Metformin
Leuprolide
Hypoglycemic Agents
Physiological Effects of Drugs
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents