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
|Condition or disease||Intervention/treatment||Phase|
|Hypogonadism Metabolic Syndrome Obesity Erectile Dysfunction||Drug: Testosterone Drug: Placebo||Phase 4|
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 (Clinical Trial)|
|Actual Enrollment :||82 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Testosterone Replacement in Metabolic Syndrome and Inflammation of Fat Tissue|
|Study Start Date :||January 2004|
|Actual Primary Completion Date :||October 2014|
|Actual Study Completion Date :||October 2014|
Experimental: Testosterone gel
Testosterone transdermal gel 50 mg/day
Testosterone transdermal gel 50 mg/day (5 gr)
Placebo Comparator: Placebo gel
Placebo transdermal gel (5 gr)
- 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.
- 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.
- 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.
- CRP (C reactive protein) [ Time Frame: 3 months ]C reactive protein (High sensitivity).
- 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)
- Adipokines [ Time Frame: 3 months ]
Estimate of within subject absolute change in serum:
ADIPONECTIN, LEPTIN, RESISTIN.
- Waist circumference [ Time Frame: 3 months ]Waist circumference (cm)
- IIEF [ Time Frame: 3 months ]International Index of Erectile Dysfunction
- Penile CDU (color Doppler ultrasound) [ Time Frame: 3 months ]Penile Color-Doppler Ultrasonography of cavernosal arteries before and after active or placebo treatment.
- PSA (prostatic specific antigen) [ Time Frame: 3 months ]PSA
- Hb, Htc [ Time Frame: 3 months ]haemoglobin and haematocrit
- Fat-free mass [ Time Frame: 6 months ]
- Fat Mass [ Time Frame: 6 months ]
- HOMA-IR [ Time Frame: 6 months ]
- CRP [ Time Frame: 6 months ]
- Interleukins [ Time Frame: 6 months ]Serum IL-1, IL-6, IL-10, IL-12, IL-2, IL-8, TNFa
- Adipokines [ Time Frame: 6 months ]Serum ADIPONECTIN, LEPTIN, RESISTIN.
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
|Dipartimento di Fisiopatologia Medica - Policlinico Umberto I|
|Rome, Italy, 00161|
|Policlinico Umberto I Hospital - Sapienza University|
|Rome, Italy, 00161|
|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|