Testosterone Replacement in Metabolic Syndrome and Inflammation (TERMSINFAT)

October 25, 2014 updated by: Andrea M. Isidori, University of Roma La Sapienza

Testosterone Replacement in Metabolic Syndrome and Inflammation of Fat Tissue

Hypogonadism (HG) frequently complicates the Metabolic Syndrome (MetS), whether testosterone replacement (TRT) is beneficial has not been clearly ascertained. This study was designed to address the effects of TRT on insulin resistance, body composition and pro-inflammatory status in naïve patients with MetS and HG.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The features of Metabolic Syndrome (MetS) include abdominal obesity, atherogenic dyslipidemia, raised blood pressure, insulin resistance or glucose intolerance. These symptoms are also frequently found in hypogonadal men.

Adipose tissue and androgens in male obesity are reciprocally linked. Total and free testosterone (T) are decreased in proportion to the degree of body fatness while T regulates insulin sensitivity and body composition. As a consequence, hypoandrogenism carries an additional independent risk for cardiovascular and metabolic disorders. Men with type 2 diabetes mellitus (T2D) exhibit lowered T levels that are inversely correlated to HbA1c. In addition, abdominal adiposity causes an impairment of testicular steroidogenesis that is directly linked to circulating adipokines; enhanced cytokine release from macrophage-infiltrated adipose tissue is pivotal to the pathogenesis of insulin resistance and atherosclerosis. Both MetS and T2D share with hypogonadism such a proinflammatory state.

For this reason we performed a randomized controlled trial on the effects of TRT on insulin resistance and circulating inflammatory markers in a cohort of middle-aged men with mild hypogonadism and MetS at first diagnosis, that were not taking medications known to influence the investigated outcomes. We established strict criteria for enrollment and used a physiological replacing therapy.

Given that testosterone replacement therapy (TRT) determines a reduction of body fat mass paralleled by an increase in fat free mass (6), and that TRT exerts an anti-inflammatory role inhibiting interleukins (IL), in particular the IL-6 gene (14), it remains to be established whether these independent effects also reflect in an improvement in insulin resistance.

Study Type

Interventional

Enrollment (Actual)

82

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Rome, Italy, 00161
        • Dipartimento di Fisiopatologia Medica - Policlinico Umberto I
      • Rome, Italy, 00161
        • Policlinico Umberto I Hospital - Sapienza University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • patients with Metabolic Syndrome according to ATPIII
  • patients with mild hypogonadism (both testosterone evaluations between 6 and 11 nmol/L)
  • patients naïve to hypoglycemic therapies

Exclusion Criteria:

  • patients on hypoglycemic medications
  • patients with severe hypogonadism (<5 nmol/L)
  • patients with borderline T values hypogonadism (>11 nmol/L)
  • patients with contraindication to testosterone therapy: prostate cancer, PSA>4 ng/ml, severe hepatic or renal insufficiency, Hb>17, Htc>52%, severe urinary retention

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo gel
Drug: Placebo
Placebo transdermal gel (5 gr)
Experimental: Testosterone gel
Testosterone transdermal gel 50 mg/day
Drug: Testosterone
Testosterone transdermal gel 50 mg/day (5 gr)
Other Names:
  • Androgel
  • Testogel

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Fat-Free Mass (kg)
Time Frame: 3 months
Estimate of within subject absolute change in fat-free mass measured by DEXA (dual energy x-ray absorptiometry) at 3 months (90 days) interval during active or placebo treatment.
3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
HOMA-IR
Time Frame: 6 months
6 months
CRP
Time Frame: 6 months
6 months
Fat Mass (kg)
Time Frame: 3 months
Estimate of within subject absolute change (Kg) in fat mass measured by DEXA at 3 months (90 days) interval during active or placebo treatment.
3 months
HOMA-IR (homeostasis model assessment)- (insulin resistance)
Time Frame: 3 months
Estimate of within subject absolute change in measure of insulin resistance homeostatic model HOMA-IR.
3 months
CRP (C reactive protein)
Time Frame: 3 months
C reactive protein (High sensitivity).
3 months
Interleukins
Time Frame: 3 months

Within subject absolute and percentage change in serum:

IL-1, IL-6, IL-10, IL-12, IL-2, IL-8, TNFa (tumor necrosis factor alpha)
3 months
Adipokines
Time Frame: 3 months

Estimate of within subject absolute change in serum:

ADIPONECTIN, LEPTIN, RESISTIN.
3 months
Waist circumference
Time Frame: 3 months
Waist circumference (cm)
3 months
IIEF
Time Frame: 3 months
International Index of Erectile Dysfunction
3 months
Penile CDU (color Doppler ultrasound)
Time Frame: 3 months
Penile Color-Doppler Ultrasonography of cavernosal arteries before and after active or placebo treatment.
3 months
PSA (prostatic specific antigen)
Time Frame: 3 months
PSA
3 months
Hb, Htc
Time Frame: 3 months
haemoglobin and haematocrit
3 months
Fat-free mass
Time Frame: 6 months
6 months
Fat Mass
Time Frame: 6 months
6 months
Interleukins
Time Frame: 6 months
Serum IL-1, IL-6, IL-10, IL-12, IL-2, IL-8, TNFa
6 months
Adipokines
Time Frame: 6 months
Serum ADIPONECTIN, LEPTIN, RESISTIN.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Roma La Sapienza

Investigators

  • Principal Investigator: Vincenzo Bonifacio, MD, PhD, University of Roma La Sapienza
  • Study Director: Andrea M Isidori, MD, PhD, University of Roma La Sapienza
  • Study Chair: Andrea Lenzi, MD, PhD, University of Roma La Sapienza

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2004

Primary Completion (Actual)

October 1, 2014

Study Completion (Actual)

October 1, 2014

Study Registration Dates

First Submitted

May 10, 2010

First Submitted That Met QC Criteria

May 11, 2010

First Posted (Estimate)

May 14, 2010

Study Record Updates

Last Update Posted (Estimate)

October 28, 2014

Last Update Submitted That Met QC Criteria

October 25, 2014

Last Verified

October 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TestoMet05

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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