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Testosterone Replacement in Metabolic Syndrome and Inflammation (TERMSINFAT)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Andrea M. Isidori, University of Roma La Sapienza
ClinicalTrials.gov Identifier:
NCT01123278
First received: May 10, 2010
Last updated: October 25, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Hypogonadism
Metabolic Syndrome
Obesity
Erectile Dysfunction
Drug: Testosterone
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Testosterone Replacement in Metabolic Syndrome and Inflammation of Fat Tissue

Resource links provided by NLM:


Further study details as provided by University of Roma La Sapienza:

Primary Outcome Measures:
  • Fat-Free Mass (kg) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Fat Mass (kg) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Estimate of within subject absolute change (Kg) in fat mass measured by DEXA at 3 months (90 days) interval during active or placebo treatment.

  • HOMA-IR (homeostasis model assessment)- (insulin resistance) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Estimate of within subject absolute change in measure of insulin resistance homeostatic model HOMA-IR.

  • CRP (C reactive protein) [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    C reactive protein (High sensitivity).

  • Interleukins [ Time Frame: 3 months ] [ Designated as safety issue: No ]

    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)


  • Adipokines [ Time Frame: 3 months ] [ Designated as safety issue: No ]

    Estimate of within subject absolute change in serum:

    ADIPONECTIN, LEPTIN, RESISTIN.


  • Waist circumference [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Waist circumference (cm)

  • IIEF [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    International Index of Erectile Dysfunction

  • Penile CDU (color Doppler ultrasound) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Penile Color-Doppler Ultrasonography of cavernosal arteries before and after active or placebo treatment.

  • PSA (prostatic specific antigen) [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    PSA

  • Hb, Htc [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    haemoglobin and haematocrit

  • Fat-free mass [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Fat Mass [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • HOMA-IR [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • CRP [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Interleukins [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Serum IL-1, IL-6, IL-10, IL-12, IL-2, IL-8, TNFa

  • Adipokines [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Serum ADIPONECTIN, LEPTIN, RESISTIN.


Enrollment: 82
Study Start Date: January 2004
Study Completion Date: October 2014
Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Testosterone gel
Testosterone transdermal gel 50 mg/day
Drug: Testosterone
Testosterone transdermal gel 50 mg/day (5 gr)
Other Names:
  • Androgel
  • Testogel
Placebo Comparator: Placebo gel
Placebo gel
Drug: Placebo
Placebo transdermal gel (5 gr)

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01123278

Locations
Italy
Dipartimento di Fisiopatologia Medica - Policlinico Umberto I
Rome, Italy, 00161
Policlinico Umberto I Hospital - Sapienza University
Rome, Italy, 00161
Sponsors and Collaborators
University of Roma La Sapienza
Investigators
Principal Investigator: Vincenzo Bonifacio, MD, PhD Sapienza University of Rome
Study Director: Andrea M Isidori, MD, PhD Sapienza University of Rome
Study Chair: Andrea Lenzi, MD, PhD Sapienza University of Rome
  More Information

Publications:

Responsible Party: Andrea M. Isidori, Professor of Endocrinology, University of Roma La Sapienza
ClinicalTrials.gov Identifier: NCT01123278     History of Changes
Other Study ID Numbers: TestoMet05
Study First Received: May 10, 2010
Last Updated: October 25, 2014
Health Authority: Italy: National Institute of Health

Keywords provided by University of Roma La Sapienza:
Adiponectin
Resistin
Adipocytes
Testosterone
Aging
HOMA-IR
Insulin
Hypogonadism
Metabolic Syndrome
Obesity
Erectile Dysfunction

Additional relevant MeSH terms:
Erectile Dysfunction
Hypogonadism
Inflammation
Metabolic Syndrome X
Obesity
Syndrome
Body Weight
Disease
Endocrine System Diseases
Genital Diseases, Male
Glucose Metabolism Disorders
Gonadal Disorders
Hyperinsulinism
Insulin Resistance
Mental Disorders
Metabolic Diseases
Nutrition Disorders
Overnutrition
Overweight
Pathologic Processes
Sexual Dysfunction, Physiological
Sexual Dysfunctions, Psychological
Sexual and Gender Disorders
Signs and Symptoms
Methyltestosterone
Testosterone
Testosterone 17 beta-cypionate
Testosterone enanthate
Testosterone undecanoate
Anabolic Agents

ClinicalTrials.gov processed this record on November 27, 2014