Effects of Testosterone Undecanoate vs Placebo on Intrahepatic Fat Content in Overweight/Obese Men With T2DM or Prediabetes and Hypogonadism

NCT03851627 | Recruiting Phase 4

• 2 other identifiers: T2F120172017-001611-37
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

The epidemics of obesity, MeTSy, T2DM and CVD are increasing worldwide. Non-alcoholic fatty liver disease (NAFLD) is becoming recognized as a condition possibly involved in the pathogenesis of these diseases. The prevailing hypothesis for NAFLD pathogenesis is the 'two-hit' model, with insulin resistance and hyperinsulinemia playing essential roles, which have a plethora of effects on hepatic lipid metabolism and can lead to accumulation of triglycerides in hepatocytes. Accepted treatment for NAFLD is lifestyle modifications. Sex hormones might be relevant in T2DM development and treatment. Low testosterone (T) has deteriorating effects on glucose levels, and aggravates in obesity as aromatization of T is enhanced. T deficiency is related to increases of visceral fat accumulation and associated with development of NAFLD. T replacement might be a successful way in hypogonadism to treat obesity and counteract progression of MEtSy,T2DM or CVD driven by visceral fat accumulation or NAFLD. Primary Objective To investigate the effects on hepatic lipid content reduction of a therapy with Testosterone undecanoate 1000mg compared to placebo given for 52 weeks in patients with type 2 diabetes mellitus and hypogonadism.

Conditions

Fatty Liver; Overweight/Obesity; Prediabetes/Type2 Diabetes Mellitus; Hypogonadism, Male

Outcome Measures

Primary Outcomes (1)

• Liver fat

  Change in Liver fat content

  baseline to week 52, and after 2 years follow up

Secondary Outcomes (9)

• body weight

  baseline to week 52, and after 2 years follow up

• waist, hip and neck circumference

  baseline to week 52, and after 2 years follow up

• insulin sensitivity

  baseline to week 52, and after 2 years follow up

• Level of HbA1c

  baseline to week 52, and after 2 years follow up

• Concentration of lipids

  baseline to week 52, and after 2 years follow up

Other Outcomes (14)

• amount of body fat

  baseline to week 52, and after 2 years follow up

• level of HbA1c

  baseline to week 52, and after 2 years follow up

• HbA1c reduction >=0.5%

  baseline to week 52, and after 2 years follow up

Study Arms (2)

Testosterone undecanoate

ACTIVE COMPARATOR

intramuscular Testosterone undecanoate 1000mg/4ml

Drug: Testosterone Undecanoate

Testosterone like Placebo

PLACEBO COMPARATOR

intramuscular Testosterone undecanoate like Placebo

Drug: Placebo

Interventions

Testosterone Undecanoate DRUG

1000mg/4ml i.m. initial, after 6 weeks, every 10 weeks thereafter

Also known as: Nebido

Testosterone undecanoate

Placebo DRUG

Placebo Arm

Also known as: oily solution, Nebido like Placebo

Testosterone like Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• prediabetes/T2DM
• male sex
• HbA1c \>=5.7% -9.0% or fasting glucose \>=100mg/dl or postprandial glucose\>= 140mg/dl
• Age \>=18 -75 years
• BMI\>=25kg/m²
• Hypogonadism assessed by laboratory testing (testosterone \< 4,04ng/ml (=14nmol/l) Metformin 8 weeks stable dose, SGLT2 inhibitors 3 months stable dose, DPP4 inhibitors 3 months stable dose, GLP1 RA 3 months stable dose and long acting insulin (basal insulin) 8 weeks stable dose
• able and willing to not change diet and physical activity during enrollment in study
• consent and able to give informed consent.

You may not qualify if:

• Current testosterone treatment or testosterone replacement within the last 12 month
• Serum creatinine\>1,5mg/dl
• Liver enzymes above 3 fold normal range
• PSA\>4.0μg/l
• Hematocrit\>50%
• Known intolerance to testosterone undecanoate or any of its ingredients
• Myocardial infarction within the last 12month
• Stroke within the last 12 month
• Untreated congestive heart disease
• malignancy within the last 5 years before randomization
• Prostate cancer or any suspicion thereof
• Breast cancer
• Liver tumor/cancer
• Epilepsy
• Migraine

Sponsors & Collaborators

• Alexandra Kautzky-Willer: lead
• Bayer: collaborator

Study Sites (1)

Abt. für Endokrinologie & Stoffwechsel, Univ. Klin f. Innere Medizin III

Vienna, 1090, Austria

RECRUITING

MeSH Terms

Conditions

Fatty Liver; Overweight; Obesity; Prediabetic State; Eunuchism

Interventions

testosterone undecanoate

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hypogonadism; Gonadal Disorders

Study Officials

• Alexandra Kautzky-Willer, MD

  Medical University Vienna

  PRINCIPAL INVESTIGATOR

• Jürgen Harreiter, PhD

  Medical University Vienna

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jürgen Harreiter, PhD

CONTACT

+43 1 40400; juergen.harreiter@meduniwien.ac.at

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head of Department of Endocrinology, Principal Investigator

Study Record Dates

• First Submitted: January 14, 2019
• First Posted: February 22, 2019
• Study Start: January 25, 2022
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: March 13, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: beginning 6 months and ending 24 months following article publication
• Access Criteria: Researches who provide a methodologically sound proposal. Please send the proposal to juergen.harreiter@meduniwien.ac.at. A data access agreement needs to be signed.

Locations

AU (1)