Testosterone Replacement in Metabolic Syndrome and Inflammation (TERMSINFAT)
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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 |
- 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.
- 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.
| Estimated Enrollment: | 70 |
| Study Start Date: | January 2004 |
| Estimated Study Completion Date: | October 2013 |
| Estimated Primary Completion Date: | August 2013 (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:
|
|
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 |
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| Contact: Vincenzo Bonifacio, MD, PhD | +39 0649970540 | vincenzobonifacio@yahoo.it |
| Italy | |
| Dipartimento di Fisiopatologia Medica - Policlinico Umberto I | Completed |
| Rome, Italy, 00161 | |
| Policlinico Umberto I Hospital - Sapienza University | Recruiting |
| Rome, Italy, 00161 | |
| Contact: Andrea M Isidori, MD, PhD +39 0649970540 andrea.isidori@uniroma1.it | |
| Principal Investigator: Andrea M Isidori, MD, PhD | |
| Sub-Investigator: Elisa Giannetta, MD | |
| Principal Investigator: Vincenzo Bonifacio, MD, PhD | |
| Sub-Investigator: Antonello Radicioni, MD | |
| Sub-Investigator: Antonio Aversa, MD, PhD | |
| Sub-Investigator: Carlotta Pozza | |
| 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: | May 5, 2013 |
| 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:
|
Hypogonadism Inflammation Obesity Erectile Dysfunction Metabolic Syndrome X Gonadal Disorders Endocrine System Diseases Pathologic Processes Overnutrition Nutrition Disorders Overweight Body Weight Signs and Symptoms Sexual Dysfunction, Physiological Genital Diseases, Male |
Sexual Dysfunctions, Psychological Sexual and Gender Disorders Mental Disorders Insulin Resistance Hyperinsulinism Glucose Metabolism Disorders Metabolic Diseases Testosterone Testosterone enanthate Testosterone undecanoate Testosterone 17 beta-cypionate Methyltestosterone Androgens Hormones Hormones, Hormone Substitutes, and Hormone Antagonists |
ClinicalTrials.gov processed this record on May 22, 2013