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Insulin Resistance and Testosterone in Women

Primary Purpose

Insulin Resistance, Postmenopause

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

metformin

leuprolide injection

placebo pill

placebo injection

About this trial

This is an interventional treatment trial for Insulin Resistance

Eligibility Criteria

50 Years - 79 Years (Adult, Older Adult)FemaleAccepts Healthy Volunteers

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

Sites / Locations

University of Pennsylvania Clinical and Translational Research Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm Description

metformin pill plus placebo injection

leuprolide injection plus placebo pill

placebo pill plus placebo injection

Outcomes

Primary Outcome Measures

Percent Change in Free Testosterone (T)

Percent change in free T by equilibrium dialysis between baseline and 12 weeks

Change in Insulin Sensitivity

Change in insulin sensitivity (mg/kg/min) calculated from hyperinsulinemic euglycemic clamp

Secondary Outcome Measures

Percent Change in Luteinizing Hormone (LH) From Baseline

Percent Change in Homeostasis Model Assessment Index of Insulin Resistance (HOMA-IR)

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.

Percent Change in Low Density Lipoprotein (LDL)

Percent Change in Systolic Blood Pressure

Free T and IR in Women in Whom Metabolic Syndrome is Present vs. Absent

Dehydroepiandrosterone Sulfate (DHEA-S)

Body Mass Index (BMI)

Full Information

NCT ID

NCT00123110

First Posted

July 19, 2005

Last Updated

May 21, 2019

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.

1. Study Identification

Unique Protocol Identification Number

NCT00123110

Brief Title

Insulin Resistance and Testosterone in Women

Official Title

Insulin Resistance and Testosterone in Non-Diabetic Postmenopausal Women

Study Type

Interventional

2. Study Status

Record Verification Date

May 2019

Overall Recruitment Status

Completed

Study Start Date

July 2005 (undefined)

Primary Completion Date

December 2011 (Actual)

Study Completion Date

December 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Pennsylvania

Collaborators

4. Oversight

Data Monitoring Committee

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Insulin Resistance, Postmenopause

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

35 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

metformin pill plus placebo injection

Arm Title

Arm Type

Experimental

Arm Description

leuprolide injection plus placebo pill

Arm Title

Arm Type

Placebo Comparator

Arm Description

placebo pill plus placebo injection

Intervention Type

Drug

Intervention Name(s)

metformin

Other Intervention Name(s)

Glucophage

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

leuprolide injection

Other Intervention Name(s)

Lupron

Intervention Description

3.75 mg injection every 4 weeks (e.g. at baseline, 4, and 8 weeks)

Intervention Type

Drug

Intervention Name(s)

placebo pill

Intervention Description

matching pill twice a day for 12 weeks

Intervention Type

Drug

Intervention Name(s)

placebo injection

Intervention Description

matching injection every 4 weeks (e.g. baseline, 4, and 8 weeks)

Primary Outcome Measure Information:

Title

Percent Change in Free Testosterone (T)

Description

Percent change in free T by equilibrium dialysis between baseline and 12 weeks

Time Frame

Baseline to 12 weeks

Title

Change in Insulin Sensitivity

Description

Change in insulin sensitivity (mg/kg/min) calculated from hyperinsulinemic euglycemic clamp

Time Frame

baseline and 12 weeks

Secondary Outcome Measure Information:

Title

Percent Change in Luteinizing Hormone (LH) From Baseline

Time Frame

baseline and 12 weeks

Title

Percent Change in Homeostasis Model Assessment Index of Insulin Resistance (HOMA-IR)

Description

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.

Time Frame

baseline and 12 weeks

Title

Percent Change in Low Density Lipoprotein (LDL)

Time Frame

baseline and 12 weeks

Title

Percent Change in Systolic Blood Pressure

Time Frame

baseline and 12 weeks

Title

Free T and IR in Women in Whom Metabolic Syndrome is Present vs. Absent

Time Frame

baseline and 12 weeks

Title

Dehydroepiandrosterone Sulfate (DHEA-S)

Time Frame

baseline and 12 weeks

Title

Body Mass Index (BMI)

Time Frame

baseline and 12 weeks

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

50 Years

Maximum Age & Unit of Time

79 Years

Accepts Healthy Volunteers

Eligibility Criteria

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Anne R. Cappola, MD, ScM

Organizational Affiliation

University of Pennsylvania

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Pennsylvania Clinical and Translational Research Center

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

11790215

Citation

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. doi: 10.1001/jama.287.3.356.

Results Reference

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PubMed Identifier

15353414

Citation

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. doi: 10.1093/aje/kwh250.

Results Reference

background

PubMed Identifier

8941471

Citation

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. doi: 10.2337/diacare.19.12.1399.

Results Reference

background

PubMed Identifier

11772901

Citation

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. doi: 10.2337/diacare.25.1.55.

Results Reference

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Insulin Resistance and Testosterone in Women

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