Study on Effects of Testosterone Replacement Therapy in Hypogonadal Type 2 Diabetic Patients (SETH2)

Study Overview
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Brief Summary
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Aim of the study was to investigate the effects of testosterone replacement therapy on components of metabolic syndrome, vascular function and morphology, grade of non-alcoholic fatty liver disease (NAFLD), bone mineral density (BMD) and health-related quality of life.

Detailed Description
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Studies have shown that approximately 50 % of older obese males, who are being treated for diabetes mellitus type 2, also exhibit low testosterone levels. Hypogonadism negatively affects glycemic control, exacerbates early cardio-vascular disease, causes osteoporosis, erectile disfunction, reduces lean body mass, accelerates the accumulation of visceral fat and leads to obesity. Patients with diabetes mellitus type 2 and confirmed hypogonadism were enrolled into this randomized, double-blind, placebo-controlled clinical study. Placebo group patients were receiving placebo throughout the first year of this study and Testosterone group patients were receiving testosterone undecanoate during first year. Both groups were receiving testosterone undecanoate throughout the second year of this study.

Official Title
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Study on Effects of Testosterone Replacement Therapy in Hypogonadal Type 2

Conditions
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Hypogonadism, Male, Diabetes Mellitus, Type 2, Obesity

Intervention / Treatment
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* Drug: Testosterone Undecanoate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: men aged > 35 years body mass index > 30 kg/m2 confirmed hypogonadism type 2 diabetes mellitus treated with non-insulin therapy Exclusion Criteria: previously treated hypogonadism the 2 diabetes mellitus treated with insulin therapy a history of current prostate or breast cancer severe benign prostatic hyperplasia elevated prostate-specific antigen (PSA > 4.0 lg/l) severe heart failure acute coronary event or procedure during the six months leading up to the study chronic obstructive lung disease hypothyroidism severe obstructive sleep apnea (OSA) active infection rheumatoid arthritis

Ages Eligible for Study
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Minimum Age: 35 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 55 patients were divided in two groups. P group patients were receiving placebo throughout the first year of this study and T group patients were receiving testosterone. Both groups were receiving TRT throughout the second year.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Testosterone<br>Testosterone arm patients were receiving testosterone undecanoate 1000 mg intramuscular injections two years; according to the protocol every 10 weeks | Drug: Testosterone Undecanoate<br>* 1000 mg i.m. every 10 weeks<br>* Other names: Nebido;|
| Placebo Comparator: Placebo<br>Placebo arm patients were receiving placebo throughout the first year of this study and testosterone undecanoate 1000 mg intramuscular injections during second year. | Drug: Testosterone Undecanoate<br>* 1000 mg i.m. every 10 weeks<br>* Other names: Nebido;Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of testosterone replacement therapy on glycemic control - fasting plasma glucose (FPG) mmol/l | The primary outcome measure was change in glycemic control - fasting plasma glucose (FPG) mmol/l | FPG was measured at baseline, after 12 months and after 24 months | 
| Effects of testosterone replacement therapy on glycemic control - glycated hemoglobin A1c (HbA1c) % | The primary outcome measure was change in glycemic control - glycated hemoglobin A1c (HbA1c) % | HbA1c was measured at baseline, after 12 months and after 24 months | 
| Effects of testosterone replacement therapy on parameters of metabolic syndrome - change in HOMA-IR | The primary outcome measure was change in Homeostasis model assessment of insulin resistance (HOMA-IR) | HOMA-IR was calculated at the baseline, after 12 months and after 24 months of clinical trial. | 
| Effects of testosterone replacement therapy on vascular function - change in flow mediated dilatation (FMD) % | The primary outcome measure was change in flow mediated dilatation (FMD) % assessed by vascular ultrasound | FMD was measured at baseline, after 12 months and after 24 months | 
| Effects of testosterone replacement therapy on vascular morphology - intima-media thickness (IMT) | The primary outcome measure was change in intima-media thickness (IMT) mm assessed by vascular ultrasound | IMT was measured at baseline, after 12 months and after 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of testosterone replacement therapy on non-alcoholic fatty liver disease (NAFLD) | The secondary outcome was change in grade of non-alcoholic fatty liver disease (NAFLD) graded as either none, mild, moderate and severe, assessed by abdominal ultrasound | Grade of NAFLD was determined at baseline and after 24 months | 
| Effects of testosterone replacement therapy on bone mineral density (BMD) | The secondary outcome was change in bone mineral density assessed by dual-energy x-ray absorptiometry (DXA) g/cm^2 | Change in bone mineral density was measured at baseline and after 24 months | 
| Effects of testosterone replacement on total testosterone (TT), calculated free testosterone (cFT), and calculated bioavailable testosterone (BT) concentrations | The secondary outcome were changes in total testosterone (TT), calculated free testosterone (cFT), and calculated bioavailable testosterone (BT) concentrations - all in nmol/l | Changes in total testosterone (TT), calculated free testosterone (cFT), and calculated bioavailable testosterone (BT) concentrations were measured baseline, after 12 months and 24 months | 
| Effects of testosterone replacement on prostate specific antigen (PSA) | The secondary outcome was change in prostate specific antigen (PSA) ng/ml | Prostate specific antigen (PSA) was measured at baseline,3,6,12,15,18 and 24 months | 
| Effects of testosterone replacement on hematocrit | The secondary outcome was change in hematocrit (Hct) % | Hematocrit was measured at baseline,3,6,12,15,18 and 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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testosterone, hypogonadism, diabetes mellitus, visceral obesity, insulin resistance, metabolic syndrome, NAFLD, endothelial function