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

• Status: Not yet recruiting
• Trial end date: 2023-12-01
• Target enrollment: 0
• Participant gender: Male

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Alexandra Kautzky-Willer
• Collaborator: Bayer
• Treatments: Methyltestosterone; Testosterone; Testosterone 17 beta-cypionate; Testosterone enanthate; Testosterone undecanoate

Criteria

Inclusion Criteria:

• T2DM

• male sex

• HbA1c >=7,5% -11%

• Age >=18 -75 years

• BMI>=30kg/m²

• Hypogonadism assessed by laboratory testing (testosterone < 3,5ng/ml (=12nmol/l)

• Metformin, SGLT2 inhibitors, DPP4 inhibitors 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.

Exclusion Criteria:

• 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

• Presence of any absolute or relative contraindication for the conduct of an MRI investigation, such as cardiac pacemakers, ferromagnetic haemostatic clips in the central nervous system, metallic splinters in the eye, ferromagnetic or electronically operated active devices like automatic cardioverter defibrillators, cochlear implants, insulin pumps and nerve stimulators, prosthetic heart valves etc.

• patients on antidiabetic medication like Sulfonylurea or Glitazones, GLP1A.

• Any other clinical condition that would jeopardize patients safety while participating in this clinical trial

• Known autoimmune disease or chronic inflammatory condition

• Other liver disease including chronic viral hepatitis (B or C), alcohol abuse, hemochromatosis, alpha-1 antitrypsin deficiency, autoimmune hepatitis, Wilson's disease, primary sclerosing cholangitis or primary biliary cirrhosis, or liver cirrhosis of any etiology

• Alcohol or drug abuse within the 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to study procedures or study drug intake

• History of bariatric surgery

• Treatment with anti-obesity drugs (e.g. sibutramine, orlistat) 3 months prior to informed consent or any other treatment at the time of screening (i.e. surgery, aggressive diet regimen, etc.) leading to unstable body weight

• Subjects receiving antihypertensive medication and/or thyroid hormones, the dose(s) of which have not been stable for at least 6 weeks prior to baseline

• Uncontrolled/ untreated hypertension

• Current treatment with systemic steroids at time of informed consent. (Treatment with local and inhaled steroids is allowed)

• Donation of blood (> 400 mL) during the previous 3 months prior to the screening visit or during the duration of the study

• Participation in another trial with an investigational drug within 30 days prior to informed consent.

• Pharmacist, study coordinator, other staff thereof, directly involved in the conduct of the protocol.

• contraindication for intramuscular injection (e.g patient receiving anticoagulants on a regular basis such as NOAKs or VKAs, or DAPT).

• COPD Gold IV or recurrent acute or allergic asthma (for MPI)

• Contraindications for cardiac stress test as acute myocardial infarction, instable angina, severe hypertension, myocarditis, life threatening rhythmic disorders without physical activity.