Diabetes Mellitus Type 1
Conditions
Interventions
Trade Name: Actrapid
Product Name: Insulin human
Pharmaceutical Form: Solution for injection in cartridge
INN or Proposed INN: Actrapid
CAS Number: 11061-68-0
Other descriptive name: INSULIN HUMAN REG
Sponsors
Medizinische Universität Graz / Endokrinologie und Stoffwechsel
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial. 2. Type 1 diabetes mellitus (as diagnosed clinically) = 12 months prior to screening visit 3. Male or female, aged 18 – 64 years (both inclusive) 4. Body mass index (BMI) 18.0 - 28.0 kg/m2 (both inclusive) 5. HbA1c 42 – 80 mmol/mol (6.0-9.5%) 6. Treated with daily insulin injections or continuous s.c. insulin infusion (CSII) = 12 months. Stable insulin dose as judged by the investigator. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Known or suspected hypersensitivity to trial product(s) or related products 2. Recurrent severe hypoglycaemia (more than 1 severe hypoglycaemic event during the last 12 months) as judged by the investigator 3. Severe hypoglycaemia within 1 month of screening 4. Hypoglycaemia unawareness as judged by the Investigator or hospitalisation for diabetic ketoacidosis during the previous 6 months 5. Clinically significant abnormal haematology, biochemistry, lipids, or urinalysis or coagulation screening tests, as judged by the investigator and any of the following laboratory safety results: a. ASAT, ALAT, lipase, alkaline phosphatase > 2.0 times upper limit of reference range (ULN) b. Haemoglobin < 8.0 mmol/L (male) or < 6.4 mmol/L (female), total leukocyte count < 3.0 x 109/L, thrombocytes <100 x 109/L c. Serum creatinine levels = 126 µmol/L (male) or = 111 µmol/L (female) 6. Suffer from or history of a life threatening disease (e.g. cancer except basal cell skin cancer or squamous cell skin cancer), or any clinically significant respiratory, metabolic, renal, hepatic, gastrointestinal, endocrinological (with the exception of diabetes mellitus and euthyroid struma), haematological, dermatological, venereal, neurological, psychiatric diseases or other major disorders as judged by the investigator. 7. Cardiac problems defined as decompensated heart failure (New York Heart Association (NYHA) class III and IV) at any time and/or angina pectoris within the last 12 months prior to screening and/or acute myocardial infarction at any time. 8. Supine blood pressure at screening (after resting for 5 min) outside the range of 90-140 mmHg for systolic or 50-90 mmHg for diastolic (repeated measurement on a second screening visit allowed to exclude white-coat hypertension). This exclusion criterion also pertains to subjects being on antihypertensives. 9. Clinically significant abnormal ECG at screening, as judged by the investigator. 10. Proliferative retinopathy or maculopathy and/or severe neuropathy, in particular autonomic neuropathy, as judged by the investigator. 11. Any disease or condition that, in the opinion of the investigator, would represent an unacceptable risk for the subject’s safety. 12. Subject positive for Hepatitis B surface antigen (HBsAg) or Hepatitis C antibodies (or diagnosed with active hepatitis according to local practice). 13. Positive result of the screening test for HIV-1 antibodies, HIV-2 antibodies and/or HIV-1 antigen according to locally used diagnostic testing. 14. History of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reaction. 15. Current treatment with systemic (oral or i.v.) corticosteroids, MAO inhibitors, non-selective beta-blockers, growth hormone, herbal products or non-routine vitamins. Furthermore, thyroid hormones are not allowed unless the use of these has been stable during the past 3 months prior to screening. 16. Significant history of alcoholism or drug/chemical abuse as per investigator’s judgement or a positive result in the drug/alcohol screen at the screening visit. 17. Subject with mental incapacity or language barriers precluding adequate understanding or co operation or who, in the opinion of the investigator, should not participate in the trial. 18. Potentially non-compliant or uncooperative during the trial, as judged by the investigator. 19. Any condition that would interfere with trial participation or evaluation of results, as judged by the inves
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the feasibility and stability of determining the endogenous glucose production during a hypoglycaemic clamp in type 1 diabetes mellitus subjects by a stable tracer to tracee ratio with an enrichment of 4% and a variation below +/- 30%;Secondary Objective: To investigate the stability of the tracer to tracee ratio during the tracer steady state at the begin of the hypoglycaemic clamp with a variation below +/- 30% To investigate the effect of insulin given intravenously with an infusion rate of 1,5 mU/kg/min on the tracer to tracee ratio with a variation below +/- 30% To investigate the effect of different quantities of glucose given intravenously on the tracer to tracee ratio with a variation below +/- 30% To investigate the stability of the tracer to tracee ratio during 30 minutes at each plateau during the hypoglycaemic clamp To investigate the time to reach each glucose plateau during the hypoglycaemic clamp To investigate the glucose levels during the recovery phase ;Primary end point(s): Stable tracer to tracee ratio (4% enrichment) with a variation below +/- 30% during variable GIR from the begin of the experiment until the end of the hypoglycaemic clamp ;Timepoint(s) of evaluation of this end point: During the hypoglycaemic clamp | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • 4% of tracer to tracee ratio and MARD during the tracer steady state • 4% of tracer to tracee ratio and MARD affected by insulin infusion rate of 1.5mU/kg/min • 4% of tracer to tracee ratio and MARD affected by variable GIR • Stable tracer to tracee ratio obtained by highly i.v. insulin given during the hypoglycaemic clamp • Stable tracer to tracee ratio derived for each plateau level (5.5, 3.5 and 2.5 mmol/L and for the recovery phase 4.0 mmol/L) during the hypoglycaemic clamp • Time to reach each hypoglycaemic level (5.5, 3.5 and 2.2 mmol/L) and for the recovery phase • Stable glucose levels during the plateau (5.5, 3.5 and 2.5 mmol/L) • Glucose levels during the recovery phase ;Timepoint(s) of evaluation of this end point: During the hypoglycaemic clamp | — |
Countries
Austria
Contacts
Public ContactZentrum f. Med. Grundlagenforschung
Medizinische Universität Graz / Endokrinologie und Stoffwechsel
Outcome results
None listed