Insulin Sensitivity in Men With the Metabolic Syndrome

NCT00433173 | Suspended DMC

• 2 other identifiers: DK71168 (suspended)NIDDK # 1 RO1 DK071168-01A2
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 2

Brief Summary

The metabolic syndrome is a medical condition defined by high levels of cholesterol in the blood, high blood pressure, central obesity (gain in fat around the region of the stomach), and insulin resistance (body responds less well to insulin). This state of impaired insulin resistance can lead to type 2 diabetes mellitus, which is one of the most common metabolic disorders in the U.S. Numerous studies have shown an inverse relationship between insulin resistance and testosterone levels in men, however, causality has not been established. This protocol investigates the role of testosterone in modulating insulin sensitivity in insulin resistant states such as the metabolic syndrome. The hypothesis is that testosterone administration will improve insulin sensitivity.

Conditions

Metabolic Syndrome

Keywords

testosterone; insulin sensitivity; insulin resistance; metabolic disorders

Outcome Measures

Primary Outcomes (1)

• insulin sensitivity

  at baseline and after 3 months

Secondary Outcomes (5)

• glucose metabolism

  at baseline and after 3 months

• body composition VO2 max; resting metabolic rate; muscle biopsy analysis

  at baseline and after 3 months

• VO2 max

  at baseline and after 3 months

• resting metabolic rate

  at baseline and after 3 months

• muscle biopsy analysis

  at baseline and after 3 months

Study Arms (3)

1

PLACEBO COMPARATOR

1\) Group 1: Placebo

Procedure: intravenous glucose tolerance test; Procedure: aerobic capacity (VO2 Max); Procedure: MRI; Procedure: muscle biopsy; Procedure: measurement of resting metabolic rate (energy expenditure); Procedure: Dual energy x-ray absorptiometry; Procedure: Fasting oral glucose tolerance test

2

ACTIVE COMPARATOR

2\) Group 2: Depot GnRH agonist (Zoladex) + Testosterone + placebo

Procedure: intravenous glucose tolerance test; Drug: testosterone; Drug: goserelin acetate implant; Procedure: aerobic capacity (VO2 Max); Procedure: MRI; Procedure: muscle biopsy; Procedure: measurement of resting metabolic rate (energy expenditure); Procedure: Dual energy x-ray absorptiometry; Procedure: Fasting oral glucose tolerance test

3

ACTIVE COMPARATOR

3\) Group 3: (Zoladex + Testosterone + aromatase inhibitor (anastrozole)

Procedure: intravenous glucose tolerance test; Drug: testosterone; Drug: anastrozole; Drug: goserelin acetate implant; Procedure: aerobic capacity (VO2 Max); Procedure: MRI; Procedure: muscle biopsy; Procedure: measurement of resting metabolic rate (energy expenditure); Procedure: Dual energy x-ray absorptiometry; Procedure: Fasting oral glucose tolerance test

Interventions

intravenous glucose tolerance test PROCEDURE

The IVGTT (70) is a 4 hour study with baseline sampling for insulin and glucose, followed by the administration of 0.3 mg/kg infusion of glucose, and subsequent frequent samples through 180 minutes. At 20 minutes, subjects will receive a 0.03 U/kg infusion of regular human insulin over 45 seconds to enhance the insulin level to better help us assess the impact of insulin on glucose uptake and to facilitate minimal model analysis. The IVGTT will be administered at baseline and after 3 months.

Also known as: IVGTT

1; 2; 3

testosterone DRUG

transdermal 7.5 g/per day for 3 months

Also known as: Androgel 1%

2; 3

anastrozole DRUG

tablet (per oral) 10.0 mg/ daily 3 months

Also known as: arimidex, IND# 76,878

3

goserelin acetate implant DRUG

single depot injection 10.8 mg 3 months

Also known as: Zoladex

2; 3

aerobic capacity (VO2 Max) PROCEDURE

This test is employed to assess VO2max in all subjects. O2 and CO2 will be collected and measured from the expired air during the exercise stress test and used to calculate VO2max. This test will be administered at baseline and after 3 months.

1; 2; 3

MRI PROCEDURE

1H-MR spectroscopy will be performed to measure IMCL at baseline and after 3 months.

1; 2; 3

muscle biopsy PROCEDURE

Biopsies (20-50mg) will be obtained from the vastus lateralis muscle under local anesthesia (1% lidocaine) using a 5 mm Bergström needle (65) with suction applied. The muscle biopsy will be performed at baseline and after 3 months.

1; 2; 3

measurement of resting metabolic rate (energy expenditure) PROCEDURE

Energy expenditure in the form of resting metabolic rate (RMR) will be measured via a metabolic monitor at baseline and after 3 months.

1; 2; 3

Dual energy x-ray absorptiometry PROCEDURE

Total and regional percent body fat, fat mass, lean tissue mass and bone mineral content will be determined by DEXA (Lunar Prodigy version 8.50). DEXA provides an in vivo assessment of body composition with minimal requirements for subject cooperation and will be employed at baseline and after 3 months.

Also known as: DEXA

1; 2; 3

Fasting oral glucose tolerance test PROCEDURE

To examine glucose and insulin metabolism a standard 75g OGTT will be conducted at baseline and after 3 months.

Also known as: OGTT

1; 2; 3

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 50-75 yr
• Diagnosis of the metabolic syndrome defined by the American Heart Association/National Heart, Lung, and Blood Institute guidelines as the presence of three or more of the following:
• Waist circumference \> 102 cm
• Serum triglycerides \> 150 mg/dL
• HDL cholesterol \< 40 mg/dL
• Blood pressure \> 130 mm Hg systolic or 85 mm Hg diastolic, or treatment with anti-hypertensives
• Fasting serum glucose \> 100 mg/dL
• Plasma total testosterone level less than 300 ng/dL (1 SD below the mean for young healthy men)
• Stable weight for previous three months (no weight change greater than or equal to +/-10 lbs)
• Normal TSH, prolactin and prostate specific antigen (PSA) levels (\<2.5 ng/mL)

You may not qualify if:

• New diagnosis of type 2 diabetes as defined by the ADA criteria: fasting glucose greater than 126 mg/dL or random blood glucose greater than 200 mg/dL on two occasions, or on oral hypoglycemic agents
• Contraindication to stress testing
• Contraindication to MRI scanning (Central nervous system aneurysm clips; Implanted neural stimulator; Implanted cardiac pacemaker or defibrillator; Cochlear implant; Ocular foreign body (e.g. metal shavings); Insulin pump; Metal shrapnel or bullet)
• History of testicular disorders (i.e. cryptorchidism)
• History of bleeding disorders (i.e. thrombocytopenia) or baseline hemoglobin levels less than 12g/dL
• History of metabolic bone disease (osteoporosis, osteomalacia)
• History of prostate cancer
• History of sleep apnea (subjects will also be excluded if at their baseline assessment they admit to heavy snoring, restless sleep, and/or excessive daytime somnolence)
• Symptoms of urinary outflow obstruction (i.e. benign prostatic hypertrophy)
• Illicit drug use or heavy alcohol use (\>4 drinks/day)
• Allergic disorders
• Current medications (must exclude individuals taking the following medications):
• Testosterone,
• Cimetidine,
• Spironolactone,

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead
• American Diabetes Association: collaborator

Study Sites (2)

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, 21224, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (1)

• Caronia LM, Dwyer AA, Hayden D, Amati F, Pitteloud N, Hayes FJ. Abrupt decrease in serum testosterone levels after an oral glucose load in men: implications for screening for hypogonadism. Clin Endocrinol (Oxf). 2013 Feb;78(2):291-6. doi: 10.1111/j.1365-2265.2012.04486.x.

  PMID: 22804876 DERIVED

MeSH Terms

Conditions

Metabolic Syndrome; Insulin Resistance; Metabolic Diseases

Interventions

Glucose Tolerance Test; Testosterone; Anastrozole; Goserelin; Energy Metabolism; Absorptiometry, Photon

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Investigative Techniques; Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Metabolism; Radiography; Diagnostic Imaging; Densitometry; Photometry; Chemistry Techniques, Analytical

Study Officials

• Frances J Hayes, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH

Study Record Dates

• First Submitted: February 8, 2007
• First Posted: February 9, 2007
• Study Start: May 1, 2006
• Primary Completion: February 1, 2011
• Study Completion: March 1, 2011
• Last Updated: March 2, 2010

Record last verified: 2010-03

Locations

US (2)