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Trial record 85 of 58344 for:    Placebo

Effects of Testosterone Undecanoate vs Placebo on Intrahepatic Fat Content in Obese Men With T2DM and Hypogonadism (Test2Func)

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ClinicalTrials.gov Identifier: NCT03851627
Recruitment Status : Not yet recruiting
First Posted : February 22, 2019
Last Update Posted : February 22, 2019
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Alexandra Kautzky-Willer, Medical University of Vienna

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.


Condition or disease Intervention/treatment Phase
Fatty Liver Obesity Type2 Diabetes Mellitus Hypogonadism, Male Drug: Testosterone Undecanoate Drug: Placebo Phase 4

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: 52 Week RCT to Investigate the Effect of Testosterone Undecanoate vs Placebo on Intrahepatic Fat Content in Obese Men With T2DM and Hypogonadism and Subsequent 108 Week Open Label Phase to Investigate Effects on Cardiometabolic Parameters
Estimated Study Start Date : April 2019
Estimated Primary Completion Date : April 2023
Estimated Study Completion Date : December 2023


Arm Intervention/treatment
Active Comparator: Testosterone undecanoate
intramuscular Testosterone undecanoate 1000mg/4ml
Drug: Testosterone Undecanoate
1000mg/4ml i.m. initial, after 6 weeks, every 10 weeks thereafter
Other Name: Nebido

Placebo Comparator: Testosterone like Placebo
intramuscular Testosterone undecanoate like Placebo
Drug: Placebo
Placebo Arm
Other Name: oily solution, Nebido like Placebo




Primary Outcome Measures :
  1. Liver fat [ Time Frame: baseline to week 52, and after 2 years follow up ]
    Change in Liver fat content measured by magnetic resonance spectroscopy (MRS)


Secondary Outcome Measures :
  1. body weight [ Time Frame: baseline to week 52, and after 2 years follow up ]
    change in body weight

  2. waist, hip and neck circumference [ Time Frame: baseline to week 52, and after 2 years follow up ]
    change in waist, hip and neck circumference

  3. insulin sensitivity [ Time Frame: baseline to week 52, and after 2 years follow up ]
    change in insulin sensitivity and Insulin secretion assessed by oGTT

  4. Level of HbA1c [ Time Frame: baseline to week 52, and after 2 years follow up ]
    change in HbA1c from baseline to week 52

  5. Concentration of lipids [ Time Frame: baseline to week 52, and after 2 years follow up ]
    change in lipid profile from baseline and free fatty acids in the OGTT

  6. quality of live questionnaire [ Time Frame: baseline to week 52, and after 2 years follow up ]
    change of quality of live assessed by WHO 5 Well Being Questionnaire

  7. blood pressure [ Time Frame: baseline to week 52, and after 2 years follow up ]
    change in systolic and diastolic blood pressure

  8. sexual function questionnaire [ Time Frame: baseline to week 52, and after 2 years follow up ]
    change sexual function assessed by International Index of Erectile Dysfunction questionnaire

  9. diabetes management satisfaction questionnaire [ Time Frame: baseline to week 52, and after 2 years follow up ]
    change of diabetes management satisfaction assessed by Diabetes Treatment Satisfaction Questionnaire


Other Outcome Measures:
  1. amount of body fat [ Time Frame: baseline to week 52, and after 2 years follow up ]
    Change in body fat, liver volume, visceral adipose tissue, subcutaneous adipose tissue, total adipose tissue and total lean tissue, myocardial and pancreatic fat and ventricular function

  2. level of HbA1c [ Time Frame: baseline to week 52, and after 2 years follow up ]
    The occurrence of treat to target efficacy i.e. HbA1c < 7.0 % or < 6.5 %.

  3. HbA1c reduction >=0.5% [ Time Frame: baseline to week 52, and after 2 years follow up ]
    The occurrence of a relative efficacy response. i.e. HbA1c lowering of at least 0.5%

  4. mean daily glucose profile [ Time Frame: baseline to week 52, and after 2 years follow up ]
    The change from baseline in mean daily glucose profile assessed by 8 point glucose profiles

  5. weight [ Time Frame: baseline to week 52, and after 2 years follow up ]
    The change in weight (>5% and >10%)

  6. IMT [ Time Frame: baseline to week 52, and after 2 years follow up ]
    Change in Intima Media Thickness

  7. Albumin/ Creatinine Ratio [ Time Frame: baseline to week 52, and after 2 years follow up ]
    Change in Albumin/ Creatinine Ratio

  8. myocardial flow reserve [ Time Frame: baseline to week 52, and after 2 years follow up ]
    Change in myocardial flow reserve

  9. concentration of osteocalcin [ Time Frame: baseline to week 52, and after 2 years follow up ]
    Change in concentration of osteocalcin

  10. liver volume [ Time Frame: baseline to week 52, and after 2 years follow up ]
    Change in liver volume

  11. amount of visceral adipose tissue, [ Time Frame: baseline to week 52, and after 2 years follow up ]
    Change in amount of visceral adipose tissue,

  12. amount of subcutaneous adipose tissue, [ Time Frame: baseline to week 52, and after 2 years follow up ]
    change in amount of subcutaneous adipose tissue,

  13. amount of total lean tissue, [ Time Frame: baseline to week 52, and after 2 years follow up ]
    change in amount of total lean tissue,

  14. amount of myocardial fat [ Time Frame: baseline to week 52, and after 2 years follow up ]
    change in amount of myocardial fat

  15. amount of pancreatic fat [ Time Frame: baseline to week 52, and after 2 years follow up ]
    change in amount of myocardial fat

  16. ventricular function [ Time Frame: baseline to week 52, and after 2 years follow up ]
    change in ventricular function



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03851627


Contacts
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Contact: Jürgen Harreiter, MD +43 1 40400 ext 22280 juergen.harreiter@meduniwien.ac.at

Locations
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Austria
Abt. für Endokrinologie & Stoffwechsel, Univ. Klin f. Innere Medizin III
Wien, Austria, 1090
Sponsors and Collaborators
Alexandra Kautzky-Willer
Bayer
Investigators
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Principal Investigator: Alexandra Kautzky-Willer, MD Medical University Vienna

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Responsible Party: Alexandra Kautzky-Willer, Head of Department of Endocrinology, Principal Investigator, Medical University of Vienna
ClinicalTrials.gov Identifier: NCT03851627     History of Changes
Other Study ID Numbers: T2F12017
2017-001611-37 ( EudraCT Number )
First Posted: February 22, 2019    Key Record Dates
Last Update Posted: February 22, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual data that underlie the results reported in this article, after deidentification of this
Supporting Materials: 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.

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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

Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Fatty Liver
Hypogonadism
Eunuchism
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Liver Diseases
Digestive System Diseases
Gonadal Disorders
Testosterone
Testosterone undecanoate
Testosterone enanthate
Testosterone 17 beta-cypionate
Methyltestosterone
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Anabolic Agents