Insulin Resistance and Testosterone in Women

NCT00123110 | Completed Phase 2 Results

• 4 other identifiers: AG0031K23AG019161K23AG1916101A15P30DK019525
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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.

Conditions

Insulin Resistance; Postmenopause

Outcome Measures

Primary Outcomes (2)

• Percent Change in Free Testosterone (T)

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

  Baseline to 12 weeks

• Change in Insulin Sensitivity

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

  baseline and 12 weeks

Secondary Outcomes (7)

• Percent Change in Luteinizing Hormone (LH) From Baseline

  baseline and 12 weeks

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

  baseline and 12 weeks

• Percent Change in Low Density Lipoprotein (LDL)

  baseline and 12 weeks

• Percent Change in Systolic Blood Pressure

  baseline and 12 weeks

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

  baseline and 12 weeks

Study Arms (3)

1

EXPERIMENTAL

metformin pill plus placebo injection

Drug: metformin; Drug: placebo injection

2

EXPERIMENTAL

leuprolide injection plus placebo pill

Drug: leuprolide injection; Drug: placebo pill

3

PLACEBO COMPARATOR

placebo pill plus placebo injection

Drug: placebo pill; Drug: placebo injection

Interventions

metformin DRUG

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

Also known as: Glucophage

1

leuprolide injection DRUG

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

Also known as: Lupron

2

placebo pill DRUG

matching pill twice a day for 12 weeks

2; 3

placebo injection DRUG

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

1; 3

Eligibility Criteria

• Age: 50 Years - 79 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Pennsylvania: lead
• National Institute on Aging (NIA): collaborator
• The John A. Hartford Foundation: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• University of Pennsylvania Diabetes and Endocrinology Research Center (DERC): collaborator
• TAP Pharmaceutical Products Inc.: collaborator

Study Sites (1)

University of Pennsylvania Clinical and Translational Research Center

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (4)

• 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.

  PMID: 11790215 BACKGROUND

• 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.

  PMID: 15353414 BACKGROUND

• 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.

  PMID: 8941471 BACKGROUND

• 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.

  PMID: 11772901 BACKGROUND

MeSH Terms

Conditions

Insulin Resistance

Interventions

Metformin; Leuprolide

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Results Point of Contact

• Title: Anne R. Cappola, M.D., ScM
• Organization: University of Pennsylvania, School of Medicine

ACappola@mail.med.upenn.edu

(215) 573-5359

Study Officials

• Anne R. Cappola, MD, ScM

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2005
• First Posted: July 22, 2005
• Study Start: July 1, 2005
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: May 23, 2019
• Results First Posted: May 23, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)