Effect of Increasing Testosterone on Insulin Sensitivity in Men With the Metabolic Syndrome

The purpose of the study is to examine the effect of testosterone treatment on insulin in men with the metabolic syndrome with testosterone levels at or below the lower end of the normal range.

Study Overview

• Status: Terminated
• Conditions: Metabolic Syndrome
• Intervention / Treatment: Other: Placebo; Drug: Zoladex; Drug: Testosterone gel; Drug: Anastrozole Pill

Detailed Description

The metabolic syndrome is a medical condition defined by high cholesterol levels, high blood pressure, increased abdominal obesity (gain in fat around the region of the stomach), and insulin resistance. Insulin is the hormone that your body produces to decrease the levels of sugar in your blood. A person that is insulin resistant needs more insulin to decrease blood sugar levels than a normal person does. Insulin resistance can lead to type 2 diabetes, which is one of the most common illnesses in the United States.

There is evidence pointing to a relationship between insulin and testosterone in men (testosterone is the male sex hormone that is produced in the testes). As men get older their testosterone levels decrease while their weight and insulin resistance tends to increase. The purpose of this research study is to learn more about the details of the relationship between insulin and testosterone. A clearer understanding of this relationship can have an important impact on public health due to the high rate of health problems associated with diabetes, obesity, and heart disease.

We are looking for men between the ages of 50-75 with the metabolic syndrome to participate in this research study. Participation in this study involves taking medication and/or placebo (a placebo looks exactly like the study medication but contains no active drug), blood tests, muscle biopsies, and imaging scans. This study involves outpatient visits. Subjects are paid up to $500 for completing the study.

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

Stable weight for previous three months (no weight change greater than or equal to +/-10 lbs)

Exclusion Criteria:

• No new diagnosis of type 2 diabetes or on oral hypoglycemic agents
• No history of testicular disorders
• No history of bleeding disorders (i.e. Pulmonary Embolism, Deep Vein Thrombosis, stroke, hypercoagulable syndrome)
• No history of prostate cancer
• No previous diagnosis of osteoporosis
• No 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)
• No symptoms of urinary outflow obstruction or medications for prostate disease
• No illicit drug use or heavy alcohol use (>4 drinks/day)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo injection, gel and pill	Other: Placebo
Active Comparator: Testosterone only; Zoladex 3.6 mg IM injection Testosterone 7.5 g gel (AndroGel) transdermally daily Anastrozole 10 mg (Arimidex) orally daily	Drug: Zoladex; Drug: Testosterone gel; Other Names: AndroGel; Drug: Anastrozole Pill; Other Names: Arimidex
Active Comparator: Testosterone and Estrogen; Zoladex 3.6 mg IM injection Testosterone 7.5 g gel (AndroGel) transdermally Placebo pill orally daily	Drug: Zoladex; Drug: Testosterone gel; Other Names: AndroGel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin sensitivity	Assessed by euglycemic-hyperinsulinemic clamp	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resting energy expenditure	Indirect calorimetry	3 months
Lipid profile	Fasting lipids	3 months
Body composition	DXA scan	3 months
Intramyocellular fat	MR spectroscoopy	3 months

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: National Institutes of Health (NIH); American Diabetes Association
• Investigators: Principal Investigator: Frances J Hayes, MD, Massachusetts General Hospital

Publications and helpful links

General Publications

• Pitteloud N, Hardin M, Dwyer AA, Valassi E, Yialamas M, Elahi D, Hayes FJ. Increasing insulin resistance is associated with a decrease in Leydig cell testosterone secretion in men. J Clin Endocrinol Metab. 2005 May;90(5):2636-41. doi: 10.1210/jc.2004-2190. Epub 2005 Feb 15.
• Pitteloud N, Mootha VK, Dwyer AA, Hardin M, Lee H, Eriksson KF, Tripathy D, Yialamas M, Groop L, Elahi D, Hayes FJ. Relationship between testosterone levels, insulin sensitivity, and mitochondrial function in men. Diabetes Care. 2005 Jul;28(7):1636-42. doi: 10.2337/diacare.28.7.1636.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (Actual): February 26, 2010
• Study Completion (Actual): February 26, 2010

Study Registration Dates

• First Submitted: February 20, 2007
• First Submitted That Met QC Criteria: February 20, 2007
• First Posted (Estimate): February 22, 2007

Study Record Updates

• Last Update Posted (Actual): April 18, 2017
• Last Update Submitted That Met QC Criteria: April 14, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: diabetes; obesity; Overweight; aging; metabolic syndrome; testosterone
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Disease; Hyperinsulinism; Syndrome; Metabolic Syndrome; Insulin Resistance; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Androgens; Goserelin; Testosterone; Anastrozole
• Other Study ID Numbers: 2003-P-001526

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No