Mechanisms of Glucose Counterregulation in Pancreatic Islet Transplantation

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Thomas Linn, University of Giessen
ClinicalTrials.gov Identifier:
NCT01668485
First received: August 13, 2012
Last updated: August 17, 2012
Last verified: August 2012
  Purpose

Pancreatic islet transplantation improves glucose counterregulation and stabilizes glycemic control in patients with type 1 diabetes mellitus prone to severe hypoglycemia even if insulin independence is not achieved. However, the extent and underlying metabolic pathways of this improvement are unknown. Investigators therefore compare systemic glucose turnover including lactate gluconeogenesis and muscle glucose utilization, between insulin-requiring islet transplant recipients, matched type 1 diabetic subjects who did not receive islet transplantation, and matched healthy non-diabetic subjects.


Condition Intervention Phase
Type 1 Diabetes Mellitus
Procedure: Hypoglycemic and euglycemic glucose clamp
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Basic Science
Official Title: Metabolic Studies in Type 1 Diabetic Patients After Allogenic Intraportal Islet Transplantation.

Resource links provided by NLM:


Further study details as provided by University of Giessen:

Primary Outcome Measures:
  • Whole body glucose counterregulation [ Time Frame: 6-8 weeks ] [ Designated as safety issue: No ]
    Whole body glucose counterregulation is the difference in glucose infusion rates required to maintain the glycemic goal between the hypoglycemic and euglycemic clamp. Clamps were performed at two time points at least two weeks apart. Participants will be followed for the duration of 6-8 weeks to perform the hypoglycemic and euglycemic clamp tests.


Secondary Outcome Measures:
  • Systemic glucose release [ Time Frame: 6-8 weeks ] [ Designated as safety issue: No ]

    Systemic glucose release is the amount of glucose released primarily from the liver into the blood compartment during a given time. The unit of measure is μmol/kg/min.

    Participants will be followed for the duration of 6-8 weeks to perform the hypoglycemic and euglycemic clamp tests that will yield this parameter.


  • Skeletal muscle glucose disposal [ Time Frame: 6-8 weeks ] [ Designated as safety issue: No ]
    Participants will be followed for the duration of 6-8 weeks to perform the euglycemic and hypoglycemic clamp tests. The unit of measure of this parameters is μmol/kg/min.

  • Gluconeogenesis from lactate [ Time Frame: 6-8 weeks ] [ Designated as safety issue: No ]
    This parameter is determined by labelled lactate infused into the proband. The rate of the de novo synthesis of glucose (gluconeogenesis) is determined by the degree of incorporation of the lactate label into glucose molecules. The unit of measure of this parameter is μmol/kg/min.


Enrollment: 36
Study Start Date: November 2001
Study Completion Date: November 2011
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Islet transplant recipients
Hypoglycemic and euglycemic glucose clamp
Procedure: Hypoglycemic and euglycemic glucose clamp
Each study participant will be subjected to a continuous infusion of insulin at a rate of 0.8 mU·kg−1·min−1 to induce hypoglycemia (blood glucose 2.8-3 mmol/l) for 30 minutes. At least two weeks later an identical insulin infusion will be administered and euglycemia (blood glucose 5 mmol/l) will be targeted. The order of these interventions will be subject to randomization.
Placebo Comparator: Type 1 diabetic subjects
Hypoglycemic and euglycemic glucose clamp.
Procedure: Hypoglycemic and euglycemic glucose clamp
Each study participant will be subjected to a continuous infusion of insulin at a rate of 0.8 mU·kg−1·min−1 to induce hypoglycemia (blood glucose 2.8-3 mmol/l) for 30 minutes. At least two weeks later an identical insulin infusion will be administered and euglycemia (blood glucose 5 mmol/l) will be targeted. The order of these interventions will be subject to randomization.
Active Comparator: Non-diabetic subjects
Hypoglycemic and euglycemic glucose clamp
Procedure: Hypoglycemic and euglycemic glucose clamp
Each study participant will be subjected to a continuous infusion of insulin at a rate of 0.8 mU·kg−1·min−1 to induce hypoglycemia (blood glucose 2.8-3 mmol/l) for 30 minutes. At least two weeks later an identical insulin infusion will be administered and euglycemia (blood glucose 5 mmol/l) will be targeted. The order of these interventions will be subject to randomization.

Detailed Description:

Subjects (n=12 each group) undergo a hypoglycemic and a euglycemic hyperinsulinemic clamp in a randomized fashion. Systemic and skeletal muscle glucose and lactate kinetics are assessed using a combination of isotopic and forearm balance techniques.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

T1DM/ITX+

Inclusion Criteria:

  • Type 1 Diabetes
  • Pancreatic islet transplantation

Exclusion Criteria:

  • Type 2 Diabetes
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01668485

Locations
Germany
Justus Liebig University
Giessen, Hessia, Germany, 35392
Sponsors and Collaborators
University of Giessen
Investigators
Principal Investigator: Thomas Linn, MD Justus Liebig University
  More Information

No publications provided by University of Giessen

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Thomas Linn, Professor Dr. med., University of Giessen
ClinicalTrials.gov Identifier: NCT01668485     History of Changes
Other Study ID Numbers: T1DM/ITX
Study First Received: August 13, 2012
Last Updated: August 17, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University of Giessen:
Type 1 diabetes mellitus
hypoglycemia counterregulation,
pancreatic islet transplantation

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

ClinicalTrials.gov processed this record on October 30, 2014