Pilot Study Investigating the Feasibility of Determining the Endogenous Glucose Production During a Hypoglycaemia (PILOT_EGP)
Primary objective is 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%.
Population: twenty type 1 diabetic subjects
Study design: Single-center, open, non- randomized, pilot-study
|Study Design:||Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
|Official Title:||An Open, Non-randomized, Single-center Pilot Study Investigating the Feasibility of Determining the Endogenous Glucose Production During a Hypoglycaemic Clamp in Type 1 Diabetes Mellitus Subjects|
- Tracer to Tracee Ratio (the absolute relative difference ARDi ) [ Time Frame: 8 hours ] [ Designated as safety issue: No ]
- Tracer to tracee Ratio [ Time Frame: 8 hours ] [ Designated as safety issue: No ]For each subject, the mean absolute relative difference (MARD) of the tracer to tracee ratio (4% enrichment) during variable Glucose Infusion Rate from the begin of the experiment until the end of the hypoglycaemic clamp.
- Time to reach each hypoglycaemic level [ Time Frame: 8 hours ] [ Designated as safety issue: No ]The stability of the tracer to tracee ratio during constant insulin infusion rate and for the different plateau levels (5.5, 3.5 and 2.5 mmol/L and for the recovery phase 4.0 mmol/L) will be investigated in an analog way.
|Study Start Date:||January 2014|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||September 2015 (Final data collection date for primary outcome measure)|
Experimental: Insulin human (Actrapid)
At 22:00 subject will receive insulin human (Actrapid) intravenously in order to obtain a steady state of a PG level of 5.5 mmol/L overnight until approximately 08:00 in the morning of day 2. At 8:00 am, in the morning at day 2, human insulin infusion will be increased to 1.5 mU/kg/min for each subject until approx. 12 pm for hypoglycaemia induction.
Drug: Insulin human
Other Name: Actrapid
Each subject will participate on 3 Visits. The total study duration for each subject will be approximately one month.The trial can be divided into:
- Screening Visit (Visit 1)
- Hypoglycaemic clamp Visit (Visit 2)
- Follow up Visit (Visit 3)
Screening Visit (Visit1):
The subject will be asked to attend the screening visit fasting. The following data will be assessed and performed: informed consent signed and dated, inclusion and exclusion criteria for the study, a full medical history including current medication, physical examination and laboratory examination of blood/urine samples. For women in childbearing potential a urine pregnancy test will be performed.
Hypoglycaemic Visit (Visit2):
Each subject will be asked to attend the clinical unit at approximately 20:00 in the evening on day 1. Thereafter the subject will receive an insulin and glucose infusion intravenously in order to obtain a steady state of a PG level of 5.5 mmol/L overnight until approximately 08:00 in the morning of day 2. At 05:00 hours D-[6,6-2H2] glucose (100 g/l) solution will be given i.v. as a primed (9.6 mg/kg/min) for one minute and a constant (0.08 mg/kg/min) infusion until the last blood sampling of the plasma glucose level of 4.0 mmol/L will be performed.
At 08:00 hours in the morning at day 2, insulin infusion will be increased to 1.5 mU/kg/min for each subject and the Plasma Glucose will be kept at a plateau of 5.5 mmol/L by a controlled variable intravenous infusion of glucose (10% glucose enriched with 4mg [6,6-2H2] glucose /ml) for one hour. Afterwards, plasma glucose is allowed to fall to a plateau of 3.5 mmol/L, then to a nadir of 2.5 mmol/L, then to a blood glucose level of 4.0 mmol/L and finally back to a level of 5.5 mmol/L for safety reasons. Blood sampling for measurement of plasma glucose, [6,6-2H2] glucose (labelled glucose),glucagon, vital signs, hypoglycaemic symptoms questionnaire and hypoglycaemic awareness will be performed at each plasma glucose plateau. The subject will be discharged from the clinic at day 2, or later if deemed necessary by the investigator.
Follow up Visit (Visit 3):
The subject will attend the Visit 3, 3 - 10 days after Visit 2. The following data will be assessed and performed: concomitant medication, including current diabetes treatment, adverse events, a full physical examination and laboratory examination of blood/urine samples. For women in childbearing potential a urine pregnancy test will be performed.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02028078
|Medical University of Graz|
|Graz, Styria, Austria, 8036|
|Principal Investigator:||Thomas R. Pieber, MD||Medical University of Graz, Internal Medicine, Endocrinology and Metabolism|