Pilot Study Investigating the Feasibility of Determining the Endogenous Glucose Production During a Hypoglycaemia (PILOT_EGP)

This study is enrolling participants by invitation only.
Sponsor:
Information provided by (Responsible Party):
Pieber Thomas, MD, Medical University of Graz
ClinicalTrials.gov Identifier:
NCT02028078
First received: January 3, 2014
Last updated: September 17, 2014
Last verified: September 2014
  Purpose

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


Condition Intervention Phase
Type 1 Diabetes Mellitus
Drug: Insulin human
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Medical University of Graz:

Primary Outcome Measures:
  • Tracer to Tracee Ratio (the absolute relative difference ARDi ) [ Time Frame: 8 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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.


Other Outcome Measures:
  • 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.


Estimated Enrollment: 20
Study Start Date: January 2014
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Induces hypoglycaemia
Other Name: Actrapid

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

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:

    1. ASAT, ALAT, lipase, alkaline phosphatase > 2.0 times upper limit of reference range (ULN)
    2. 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
    3. 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. Subject who has donated any blood or plasma in the past month or more than 500 mL within 3 months prior to screening.
  16. Surgery or trauma with significant blood loss (more than 500 mL) within the last 3 months prior to screening.
  17. Current treatment with systemic (oral or i.v.) corticosteroids, MAO inhibitors, nonselective 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.
  18. 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.
  19. Smoker (defined as a subject who is smoking more than 5 cigarettes or the equivalent per day)
  20. Not able or willing to refrain from smoking and use of nicotine gum or transdermal nicotine patches during the inpatient period.
  21. 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.
  22. Potentially non-compliant or uncooperative during the trial, as judged by the investigator.
  23. Any condition that would interfere with trial participation or evaluation of results, as judged by the investigator.
  24. Female of child-bearing potential who is pregnant, breast-feeding or intend to become pregnant or is not using adequate contraceptive methods (adequate contraceptive methods include sterilisation, hormonal intrauterine devices, oral contraceptives, sexual abstinence or vasectomised partner).
  25. Use of drugs, which may interfere with the interpretation of trial results or are known to cause clinically relevant interference with insulin action, glucose utilisation, or recovery from hypoglycaemia
  26. Severe acute and/or chronic diseases
  27. Diseases of the skin which could interfere with application of the catheters as judged by the investigator
  28. Previous participation in this trial. Participation is defined as randomised.
  29. Receipt of any investigational medicinal product within 3 months before randomisation in this trial.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02028078

Locations
Austria
Medical University of Graz
Graz, Styria, Austria, 8036
Sponsors and Collaborators
Medical University of Graz
Investigators
Principal Investigator: Thomas R. Pieber, MD Medical University of Graz, Internal Medicine, Endocrinology and Metabolism
  More Information

Additional Information:
No publications provided

Responsible Party: Pieber Thomas, MD, Univ. Prof. Dr. med. univ, Medical University of Graz
ClinicalTrials.gov Identifier: NCT02028078     History of Changes
Other Study ID Numbers: PILOT_EGP
Study First Received: January 3, 2014
Last Updated: September 17, 2014
Health Authority: Austria: Agency for Health and Food Safety

Keywords provided by Medical University of Graz:
Endogenous glucose production
Type 1 diabetes mellitus
hypoglycaemic clamp
tracer to technique
pharmacodynamics
pharmacokinetics

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin, Globin Zinc
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014