Effect of Testosterone Gel Replacement on Fat Mass in Males With Low Testosterone Levels and Diabetes

Effect of Androgel on Total and Regional Adipose Tissue and Lean Body Mass in Type 2 Diabetic Patients With Hypogonadism

The purpose of the study is to find out the effect of replacing testosterone in the form of a gel (Androgel®) on the amount of fat mass in males with low testosterone and diabetes.

Study Overview

• Status: Withdrawn
• Conditions: Diabetes; Hypogonadism
• Intervention / Treatment: Drug: Testosterone gel; Drug: placebo

Detailed Description

Hypogonadism is associated with increase in fat mass, decrease in muscle mass, accelerated bone loss, decreased libido and effects on mood. Androgen replacement in this context is clearly beneficial, and numerous studies have demonstrated improvements in bone and muscle mass, reductions in body fat and improvement in insulin sensitivity, libido and mood following treatment. Testosterone replacement leads to a dose-dependent decrease in adipose tissue and increase in muscle mass and strength. The principal focus of the proposed research is to evaluate the effect of androgel on lean body mass and regional adipose tissue mass (including hepatic and visceral fat) in type 2 diabetic patients with hypogonadism, a population that is likely to benefit from a reduction in adipose tissue and an increase in muscle mass.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • Midland, Texas, United States, 79707
      • Diabetes Center of the Southwest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Males with age 35-75 years inclusive.
• Evidence of hypogonadism: Hypogonadism will be defined as low total testosterone (<300 ng/dL) and low calculated free testosterone (below 6.5ng/dL; calculated using testosterone and SHBG). Testosterone levels will be measured between 8 and 10 am. Subjects who have normal total but low free testosterone levels (or vice versa) will be asked to come again after one week to have their testosterone levels re-measured. They will be included in the study in their free and total testosterone levels are low on re-measurement.
• Type 2 diabetes
• Hemoglobin A1c <8.0 %
• Subjects on medications for diabetes will be allowed as long as they are on stable doses of these compounds for at least 6 weeks. The dose of thiazolidinediones will have to be stable for 3 months prior to the study. The dosage of diabetic medications will not be changed during the study.

Exclusion Criteria:

• Coronary event or procedure (myocardial infarction, unstable angina, coronary artery bypass, surgery or coronary angioplasty) in the previous four weeks
• Hepatic disease (transaminase > 3 times normal)
• Renal impairment (serum creatinine > 1.5)
• Chronic steroid therapy
• Use of testosterone or other androgens (such as DHEA) in the last 3 months
• Panhypopituitarism
• HIV or hepatitis C
• Subjects will be excluded from the study for history of prostate or breast cancer, gonadal endocrine disorders
• Current or recent history of major psychiatric illness, significant uncontrolled systemic illness
• Sleep apnea
• History of alcoholism or substance abuse within the past year
• History of taking other drugs that might interfere with the results of the study (ie, Lupron, finasteride, spironolactone, cimetidine, antiandrogens, estrogens, p450 enzyme inducers, barbiturates)
• Abnormal prostate evidenced by prostatic symptoms, prostatic masses or induration on rectal examination, elevated levels of prostate specific antigen (>4 ng/mL; subjects with PSA levels between 2.5-4 ng/mL will be permitted if prostate biopsy is negative) or positive biopsy, a urine flow rate of less than 12 mL/s, or an International Prostate Symptom Score greater than 19
• Hematocrit greater than 50%
• Body weight >300 lbs (this is the maximum weight that can be accommodated on DEXA or MRI machines.
• The subject has systolic blood pressure >170mmHg or diastolic blood pressure >100 mmHg while on or off anti-hypertensive treatment.
• Generalized skin disease that could affect the absorption of testosterone gel (ie, psoriasis);
• Morning prolactin level greater than 40 mg/mL
• Subjects with serum fasting triglyceride concentration > 500 mg/dL at screening or with history of hypertriglyceridemia-induced pancreatitis.
• Participation in any other concurrent clinical trial
• Any other life-threatening, non-cardiac disease
• Use of an investigational agent or therapeutic regimen within 30 days or 5 half-lives (which ever is longer) preceding the first dose of study medication.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; testosterone gel	Drug: Testosterone gel; Testosterone gel to be applied daily, starting does 5g.; Other Names: Androgel
Placebo Comparator: 2; placebo gel	Drug: placebo; placebo gel apply daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean absolute change in visceral adipose tissue mass in type 2 diabetic subjects with hypogonadism after 6 months of androgel therapy.	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Study the effect in type 2 diabetic subjects with hypogonadism after 6 months of androgel therapy on:	6 months
Mean absolute change in hepatic fat measured by NMR spectroscopy.	6 months
Mean absolute change in total and regional adipose tissue mass measured by DEXA	6 months
Mean absolute change in total and regional lean body mass measured by DEXA.	6 months
Mean absolute change in total body and regional (arm, leg, ribs) BMC and BMD	6 months
Mean absolute change in hip BMC and BMD (mean of two hips)	6 months
Mean absolute change in spine BMC and lumbar spine (L1-L4) BMD	6 months

Collaborators and Investigators

• Sponsor: Diabetes Center of the Southwest
• Collaborators: Solvay Pharmaceuticals
• Investigators: Principal Investigator: Sandeep Dhindsa, MBBS, Diabetes Center of the Southwest

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Anticipated): November 1, 2011
• Study Completion (Anticipated): July 1, 2012

Study Registration Dates

• First Submitted: February 23, 2007
• First Submitted That Met QC Criteria: February 26, 2007
• First Posted (Estimate): February 27, 2007

Study Record Updates

• Last Update Posted (Estimate): August 10, 2015
• Last Update Submitted That Met QC Criteria: August 6, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: diabetes; hypogonadism; lean mass; visceral fat; hepatic fat
• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Hypogonadism; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Androgens; Testosterone
• Other Study ID Numbers: GR-940