E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hypogonadism Type 2 Diabetes Cardiovascular risk |
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E.1.1.1 | Medical condition in easily understood language |
Deficiency of the male hormone Type 2 Diabetes Heart problems |
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E.1.1.2 | Therapeutic area | Body processes [G] - Metabolic Phenomena [G03] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The purpose of this study is to find out the effect of adding testosterone to the standard diabetes treatment on glucose control. The primary outcome of the study will be HbA1C ( a blood test which looks at the average blood glucose control in patients with diabetes)and fasting plasma blood sugar levels.
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E.2.2 | Secondary objectives of the trial |
To compare the impact of testosterone therapy on
I. Body composition ( measuring the body fat and lean muscle mass)
a) Waist circumference and waist hip ratio b) Body mass index c) Percentage body fat (by Tanita body fat analyzer) d) Body composition using DEXA scan
II. Insulin resistance
a) Homa – IR (Homeostatic Model of Assessment of Insulin Resistance) in patients not on insulin (three blood samples for fasting insulin samples taken 5 minutes apart with fasting glucose)
III. Lipid Profile ( cholesterol and other fat in blood)
Fasting lipid profile (total cholesterol, LDL Cholesterol, HDL- Cholesterol, Triglycerides, Lipoprotein a and ApoE)
IV. Inflammation
hsCRP, IL-6, IL6 Soluble receptor, Adiponectin, leptin, TNF alpha, IL- 10, IL-1beta, ICAM – 1, VCAM -1 and AGEs (advance glycation end products). We also intend to store blood at -70oC for later analysis.
V. Macrophage function: ( function of the scavenger cell in the blood which play a |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Men with age >18 years 2. Type 2 Diabetes mellitus 3. HbA1C >7% <9.5% 4. Confirmed hypogonadism (early morning [0800−1000 h] total testosterone [TT] ≤12 nmol/L or calculated free testosterone ≤255 pmol/L on two occasions ≥1 week apart), with at least two symptoms of hypogonadism 5. Must be naïve to androgen replacement therapy 6. If on replacement therapy for the hypopituitarism or multiple endocrine deficiencies, the subject must be on stable doses of thyroid hormone and adrenal replacement hormones for at least 14 days prior to the enrolment. 7. No contraindication to the use of the study product – testosterone undecanoate 8. Patients understands the study protocol and voluntarily agrees to participate by providing written informed consent
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E.4 | Principal exclusion criteria |
1. Inability to give informed consent 2. Polycythaemia/ Haematocrit of >0.52 3. Abnormal prostrate digital rectal examination( palpable nodule/s) or severe prostratism or elevated PSA 4. History of prostrate cancer or breast cancer 5. Patient is enrolled in another experimental trial which involves the use of an investigational drug or device, or an intervention that would interfere with the conduct of the trial 6. Patients with significant intercurrent disease like severe heart failure, kidney disease on dialysis, psychiatric illness or any other co-morbidities making them unable to attend the scheduled visits of the trial 7. History of alcohol abuse or any drug abuse in the past 2 years 8. Current use of antiandrogens, glucocorticoids ( except where used as replacement therapy), long acting opioid analgaesics( eg., methadone, buprenorphine), oestrogens, CYP3A4 inducers( eg., barbiturates) CYP3A4 inhibitors (eg., HIV antivirals, amiodarone, ketaconazole, ciprofloxacin, azithromycin etc) 9. Men seeking to father a child and have not yet completed the family.
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
To compare the impact of testosterone therapy on
I. Body composition ( measuring the body fat and lean muscle mass)
a) Waist circumference and waist hip ratio b) Body mass index c) Percentage body fat (by Tanita body fat analyzer) d) Body composition using DEXA scan
II. Insulin resistance
a) Homa – IR (Homeostatic Model of Assessment of Insulin Resistance) in patients not on insulin (three blood samples for fasting insulin samples taken 5 minutes apart with fasting glucose)
III. Lipid Profile ( cholesterol and other fat in blood)
Fasting lipid profile (total cholesterol, LDL Cholesterol, HDL- Cholesterol, Triglycerides, Lipoprotein a and ApoE)
IV. Inflammation
hsCRP, IL-6, IL6 Soluble receptor, Adiponectin, leptin, TNF alpha, IL- 10, IL-1beta, ICAM – 1, VCAM -1 and AGEs (advance glycation end products). We also intend to store blood at -70oC for later analysis.
V. Macrophage function: ( function of the scavenger cell in the blood which play a inportant role in the development of plaque in the arteries causing heart disease)
-Monocyte RNA: qPCR on specific genes involved in lipid, cholesterol, glucose metabolism and inflammation
-Primary cell culture of macrophages for further assessment of these pathways – effect of exogenous testosterone and LXR agonists and antagonists on gene expression (qPCR) and protein level (Western blotting with densitometry)
VI. Blood pressure
After rest, 2 readings 5 minutes apart. 24 hr BP monitor
VII. Renal(kidney)and Liver Function
Urinary microalbumin, serum urea, creatinine and eGFR. Standard liver function tests (ALT, AST, alkaline phosphatase and gamma GT).
VIII. Carotid Intima-Media Thickness ( measuring the thickness of carotid artery) (using Sonosite Portable Ultrasound device)
IX. DNA collection: ( optional) ( looking at the genetic code of a cell)
To look at androgen-receptor polymorphisms and its association with the above variables
X. Safety
Prostrate Specific Antigen, Haemoglobin, haematocrit
XI. Questionnaires
ADDQoL AMS (Aging Male Symptom Score) IIEF (International Index of Erectile Dysfunction) SF36 –Quality of life Questionnaire Mini mental score Validation of a new questionnaire for hypogonadism in diabetes
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Phase 1: Randomised double blinded placebo controlled trial. Phase 2 : open labelled. |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit of the last subject will be the end of the trial. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |