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Testosterone Replacement in Metabolic Syndrome and Inflammation (TERMSINFAT)

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ClinicalTrials.gov Identifier: NCT01123278
Recruitment Status : Completed
First Posted : May 14, 2010
Last Update Posted : October 28, 2014
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:
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 or disease Intervention/treatment Phase
Hypogonadism Metabolic Syndrome Obesity Erectile Dysfunction Drug: Testosterone Drug: Placebo Phase 4

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 Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 82 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Testosterone Replacement in Metabolic Syndrome and Inflammation of Fat Tissue
Study Start Date : January 2004
Primary Completion Date : October 2014
Study Completion Date : October 2014

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
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)


Outcome Measures

Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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. CRP (C reactive protein) [ Time Frame: 3 months ]
    C reactive protein (High sensitivity).

  4. 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)


  5. Adipokines [ Time Frame: 3 months ]

    Estimate of within subject absolute change in serum:

    ADIPONECTIN, LEPTIN, RESISTIN.


  6. Waist circumference [ Time Frame: 3 months ]
    Waist circumference (cm)

  7. IIEF [ Time Frame: 3 months ]
    International Index of Erectile Dysfunction

  8. Penile CDU (color Doppler ultrasound) [ Time Frame: 3 months ]
    Penile Color-Doppler Ultrasonography of cavernosal arteries before and after active or placebo treatment.

  9. PSA (prostatic specific antigen) [ Time Frame: 3 months ]
    PSA

  10. Hb, Htc [ Time Frame: 3 months ]
    haemoglobin and haematocrit

  11. Fat-free mass [ Time Frame: 6 months ]
  12. Fat Mass [ Time Frame: 6 months ]
  13. HOMA-IR [ Time Frame: 6 months ]
  14. CRP [ Time Frame: 6 months ]
  15. Interleukins [ Time Frame: 6 months ]
    Serum IL-1, IL-6, IL-10, IL-12, IL-2, IL-8, TNFa

  16. Adipokines [ Time Frame: 6 months ]
    Serum ADIPONECTIN, LEPTIN, RESISTIN.


Eligibility Criteria

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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
First Posted: May 14, 2010    Key Record Dates
Last Update Posted: October 28, 2014
Last Verified: October 2014

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

Additional relevant MeSH terms:
Syndrome
Inflammation
Metabolic Syndrome X
Erectile Dysfunction
Hypogonadism
Disease
Pathologic Processes
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Sexual Dysfunction, Physiological
Genital Diseases, Male
Sexual Dysfunctions, Psychological
Mental Disorders
Gonadal Disorders
Endocrine System Diseases
Testosterone
Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Methyltestosterone
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Anabolic Agents