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Completed

NCT Number: NCT01123278

Testosterone Replacement in Metabolic Syndrome and Inflammation

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.

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Key information

Conditions

Hypogonadism Body Weight Endocrine System Diseases Erectile Dysfunction Genital Diseases Genital Diseases, Male Glucose Metabolism Disorders Gonadal Disorders Hyperinsulinism Insulin Resistance Male Urogenital Diseases Mental Disorders Metabolic Diseases Metabolic Syndrome Nutrition Disorders Nutritional and Metabolic Diseases Obesity Overnutrition Overweight Pathological Conditions, Signs and Symptoms Sexual Dysfunction, Physiological Sexual Dysfunctions, Psychological Signs and Symptoms Urogenital Diseases

Age range

18 year–75 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 4

Primary location

Policlinico Umberto I Hospital - Sapienza University, Rome, Italy

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Testosterone

Drug

Testosterone transdermal gel 50 mg/day (5 gr)

Other names: Androgel, Testogel

Placebo

Drug

Placebo transdermal gel (5 gr)

Primary outcomes

  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 outcomes

  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.

Sponsors and collaborators

Lead sponsor

University of Roma La Sapienza

Other

Registry information

Official study title

Testosterone Replacement in Metabolic Syndrome and Inflammation of Fat Tissue

Acronym: TERMSINFAT

Important dates

Study start
2004
Primary completion
2014
Study completion
2014
First posted
May 14, 2010
Registry last updated
Oct 28, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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