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Mechanisms of Glucose Counterregulation in Pancreatic Islet Transplantation

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ClinicalTrials.gov Identifier: NCT01668485
Recruitment Status : Completed
First Posted : August 20, 2012
Last Update Posted : August 21, 2012
Sponsor:
Information provided by (Responsible Party):
Thomas Linn, University of Giessen

Brief Summary:
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 or disease Intervention/treatment Phase
Type 1 Diabetes Mellitus Procedure: Hypoglycemic and euglycemic glucose clamp Phase 4

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Basic Science
Official Title: Metabolic Studies in Type 1 Diabetic Patients After Allogenic Intraportal Islet Transplantation.
Study Start Date : November 2001
Actual Primary Completion Date : November 2010
Actual Study Completion Date : November 2011

Resource links provided by the National Library of Medicine

Drug Information available for: Dextrose
U.S. FDA Resources

Arm Intervention/treatment
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.



Primary Outcome Measures :
  1. Whole body glucose counterregulation [ Time Frame: 6-8 weeks ]
    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 :
  1. Systemic glucose release [ Time Frame: 6-8 weeks ]

    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.


  2. Skeletal muscle glucose disposal [ Time Frame: 6-8 weeks ]
    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.

  3. Gluconeogenesis from lactate [ Time Frame: 6-8 weeks ]
    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.



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Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

T1DM/ITX+

Inclusion Criteria:

  • Type 1 Diabetes
  • Pancreatic islet transplantation

Exclusion Criteria:

  • Type 2 Diabetes

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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

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
First Posted: August 20, 2012    Key Record Dates
Last Update Posted: August 21, 2012
Last Verified: August 2012

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

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