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

NCT02028078 | Completed Phase 2 DMC

• 1 other identifier: PILOT_EGP
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Type 1 Diabetes Mellitus

Keywords

Endogenous glucose production; Type 1 diabetes mellitus; hypoglycaemic clamp; tracer to technique; pharmacodynamics; pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Tracer to Tracee Ratio (the absolute relative difference ARDi )

  8 hours

Secondary Outcomes (1)

• Tracer to tracee Ratio

  8 hours

Other Outcomes (1)

• Time to reach each hypoglycaemic level

  8 hours

Study Arms (1)

Insulin human (Actrapid)

EXPERIMENTAL

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

Interventions

Insulin human DRUG

Induces hypoglycaemia

Also known as: Actrapid

Insulin human (Actrapid)

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• )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.
• \. )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.

You may not qualify if:

• Known or suspected hypersensitivity to trial product(s) or related products
• Recurrent severe hypoglycaemia (more than 1 severe hypoglycaemic event during the last 12 months) as judged by the investigator
• Severe hypoglycaemia within 1 month of screening
• Hypoglycaemia unawareness as judged by the Investigator or hospitalisation for diabetic ketoacidosis during the previous 6 months
• 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:
• ASAT, ALAT, lipase, alkaline phosphatase \> 2.0 times upper limit of reference range (ULN)
• 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
• Serum creatinine levels ≥ 126 μmol/L (male) or ≥ 111 μmol/L (female)
• 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.
• 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.
• Clinically significant abnormal ECG at screening, as judged by the investigator.
• Proliferative retinopathy or maculopathy and/or severe neuropathy, in particular autonomic neuropathy, as judged by the investigator.
• Any disease or condition that, in the opinion of the investigator, would represent an unacceptable risk for the subject's safety.
• Subject positive for Hepatitis B surface antigen (HBsAg) or Hepatitis C antibodies (or diagnosed with active hepatitis according to local practice).
• Positive result of the screening test for HIV-1 antibodies, HIV-2 antibodies and/or HIV-1 antigen according to locally used diagnostic testing.

Sponsors & Collaborators

• Medical University of Graz: lead

Study Sites (1)

Medical University of Graz

Graz, Styria, 8036, Austria

Location

Related Publications (1)

• Zenz S, Mader JK, Regittnig W, Brunner M, Korsatko S, Boulgaropoulos B, Magnes C, Raml R, Narath SH, Eller P, Augustin T, Pieber TR. Impact of C-Peptide Status on the Response of Glucagon and Endogenous Glucose Production to Induced Hypoglycemia in T1DM. J Clin Endocrinol Metab. 2018 Apr 1;103(4):1408-1417. doi: 10.1210/jc.2017-01836.

  PMID: 29408994 DERIVED

Related Links

• Medical University of Graz

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Insulin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Thomas R. Pieber, MD

  Medical University of Graz, Internal Medicine, Endocrinology and Metabolism

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Univ. Prof. Dr. med. univ

Study Record Dates

• First Submitted: January 3, 2014
• First Posted: January 6, 2014
• Study Start: January 1, 2014
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: September 12, 2016

Record last verified: 2016-09

Locations

AU (1)