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

Study on Effects of Testosterone Replacement Therapy in Hypogonadal Type 2

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.

Study Overview

• Status: Completed
• Conditions: Obesity; Diabetes Mellitus, Type 2; Hypogonadism, Male
• Intervention / Treatment: Drug: Placebo; Drug: Testosterone Undecanoate

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Testosterone; Testosterone arm patients were receiving testosterone undecanoate 1000 mg intramuscular injections two years; according to the protocol every 10 weeks	Drug: Testosterone Undecanoate; 1000 mg i.m. every 10 weeks; Other Names: Nebido
PLACEBO_COMPARATOR: Placebo; Placebo arm patients were receiving placebo throughout the first year of this study and testosterone undecanoate 1000 mg intramuscular injections during second year.	Drug: Placebo; Drug: Testosterone Undecanoate; 1000 mg i.m. every 10 weeks; Other Names: Nebido

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Medical Centre Ljubljana
• Investigators: Principal Investigator: Kristina Groti Antonic, MD, PhD, University Medical Centre Ljubljana

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 10, 2014
• Primary Completion (ACTUAL): March 5, 2015
• Study Completion (ACTUAL): March 5, 2018

Study Registration Dates

• First Submitted: December 27, 2018
• First Submitted That Met QC Criteria: January 2, 2019
• First Posted (ACTUAL): January 3, 2019

Study Record Updates

• Last Update Posted (ACTUAL): January 4, 2019
• Last Update Submitted That Met QC Criteria: January 2, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: hypogonadism; NAFLD; insulin resistance; metabolic syndrome; diabetes mellitus; endothelial function; testosterone; visceral obesity
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Gonadal Disorders; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypogonadism; Eunuchism; Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Androgens; Anabolic Agents; Testosterone; Methyltestosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate
• Other Study ID Numbers: SBCE-KG-2014-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No