Impact of Hypoglycemia Unawareness on Brain Metabolism Cognition in T1DM

This study has been completed.
Sponsor:
Collaborators:
University of Miami
University of Minnesota - Clinical and Translational Science Institute
Information provided by (Responsible Party):
Robert Sherwin, Yale University
ClinicalTrials.gov Identifier:
NCT00575783
First received: December 14, 2007
Last updated: January 25, 2012
Last verified: January 2012

December 14, 2007
January 25, 2012
August 2005
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Complete list of historical versions of study NCT00575783 on ClinicalTrials.gov Archive Site
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Impact of Hypoglycemia Unawareness on Brain Metabolism Cognition in T1DM
Impact of Hypoglycemia Unawareness on Brain Metabolism Cognition in T1DM

The research study is designed to examine the impact of low blood sugar on brain function in individuals with Type 1 Diabetes who have frequent and severe hypoglycemia (low blood sugar) compared to those who do not.

During the course of treating diabetes (for example, after an insulin injection), blood sugar levels will sometimes drop too low. This condition is known as hypoglycemia. Normally, a healthy body responds to hypoglycemia by producing a number of "anti-insulin" hormones which raise blood sugar levels. In addition, these hormones provide the individual with warning signals of hypoglycemia, including hunger, sweating, shaking and heart palpitations. These warning signals allow diabetics to correct low blood sugar levels by eating sugar tablets or by having a snack.

Unfortunately, and for unclear reasons, many people with longstanding diabetes lose their ability to recognize low blood sugar levels-a condition called "hypoglycemia unawareness." The brain, in particular, is extremely sensitive to hypoglycemia. Unable to sense and respond to low blood sugar levels, these individuals may experience a sudden onset of blurred vision, confusion, seizures, coma, or even death.

In recent years, a new technique called "islet cell transplantation" has been developed as an alternate means of treating insulin-dependent diabetes. Pancreatic islet cells (the cells that produce insulin), from human donors, are injected into the diabetic patient's liver where the cells are capable of making insulin and can regulate blood sugar levels without the need for insulin injections. Currently, this technique is used primarily in patients with severe hypoglycemia unawareness.

While it is known that islet cell transplantation can reduce the risk of severe hypoglycemia, the effects of transplantation on hypoglycemia unawareness are unknown. This study is designed to investigate why hypoglycemia unawareness happens and the impact it has on brain function in individuals with type 1 diabetes.

Observational
Observational Model: Case Control
Time Perspective: Cross-Sectional
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Non-Probability Sample

Group 1A) T1DM subjects with severe hypoglycemia unawareness and awaiting islet cell transplantation will be referred by participating islet transplantation centers.

Group 1B) T1DM subjects with severe hypoglycemia unawareness but not awaiting islet cell transplantation will be from the greater New Haven, CT area.

Group 2)T1DM, not optimally controlled and without hypoglycemia unawareness will be from the greater New Haven, CT area.

Group 3) Non-Diabetics from the greater New Haven CT area.

  • Type 1 Diabetes
  • Hypoglycemia
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  • 1A, 1B

    Type 1 diabetic subjects with a history of severe hypoglycemia and hypoglycemia unawareness who:

    1A) meet criteria for islet cell transplantation and are referred by a participating islet cell transplantation center

    1B) meet similar criteria but are not currently planning islet cell transplantation

  • 2
    Type 1 diabetics who are not optimally controlled (>8% HbA1c) and rarely experience hypoglycemia
  • 3
    Healthy non-diabetics
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
51
August 2008
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Inclusion Criteria:

  • Inclusion Criteria for all subjects:

    • Age 18-49
    • > 85 kg
    • BMI <27female <28 male
    • able to provide written informed consent
    • able to speak and read English fluently
    • must meet Magnetic Resonance safety evaluation

Inclusion criteria for Group 1A:

  • T1DM undergoing intensive clinical management and currently on the islet transplant list
  • History of severe hypoglycemia

Inclusion criteria for Group 1B:

  • T1DM undergoing intensive clinical management
  • History of severe hypoglycemia unawareness

Inclusion criteria for Group 2:

  • T1DM with poor glycemic control, HbA1c > 8%
  • no episodes of hypoglycemia requiring assistance from another person for at least 1 yr, no episodes in last 4 weeks, and hypoglycemia aware

Exclusion Criteria:

Group 1A: (T1DM subjects being considered for islet cell transplantation)

  • Detectable c-peptide level
  • Untreated proliferative retinopathy
  • Creatinine clearance < 65 ml/min/1.73 m2
  • Serum creatinine ≥1.5 mg/dL
  • Previous pancreas or islet transplant
  • Positive pregnancy test, or presently breast-feeding, or failure to follow effective contraceptive measures
  • Active infection including hepatitis C, hepatitis B, HIV, or TB (or under treatment for suspected TB ), or subjects with a positive PPD performed within 1 yr. of enrollment, and no history of adequate prophylaxis
  • Invasive aspergillus infection within year prior to study entry
  • Any history of malignancy except for adequately treated squamous or basal cell carcinoma of the skin
  • Active alcohol or substance abuse- includes cigarette smoking (must be abstinent for 6 months)
  • History of non-adherence to prescribed regimens
  • Psychiatric disorder making the subject not a suitable candidate for transplantation
  • Baseline Hgb < 10.5 g/dL in females, or < 13 g/dL in males; lymphopenia (<1,000/μL), or leukopenia (< 3,000 total leukocytes/μL), or an absolute CD4+ count < 500/μL
  • History of coagulopathy or medical condition requiring long-term anticoagulant therapy (e.g., warfarin) after transplantation (low-dose aspirin treatment is allowed) or patient with INR >1.5
  • Severe co-existing cardiac disease, as determined by referring center
  • Baseline liver function tests outside of normal range (an initial liver function test panel with any values >1.5 times normal upper limits will exclude a patient without a re-test; a re-test for any values between normal and 1.5 times normal will be made, and if the values remain elevated above normal, the patient will be excluded), or history of significant liver disease
  • Severe unremitting diarrhea or other gastrointestinal disorders potentially interfering with the ability to absorb oral medications
  • Addison's disease as determined by clinical history
  • Under treatment for a medical condition requiring chronic use of systemic steroids
  • Any medical condition or medication that, in the opinion of the investigators, will interfere with the safe completion of the study or study outcomes

Group 1 B: (T1DM with Severe Hypoglycemia Unawareness not on the Transplant List)

  • Detectable C-peptide level
  • Serum creatinine ≥1.5 mg/dL
  • Positive pregnancy test, or presently breast-feeding, or failure to follow effective contraceptive measures
  • Active alcohol or substance abuse- includes cigarette smoking (must be abstinent for 6 months)
  • Psychiatric disorder making the subject not a suitable candidate for transplantation
  • Baseline Hgb < 10.5 g/dL in females, or < 13 g/dL in males
  • Baseline liver function tests outside of normal range (an initial liver function test panel with any values >1.5 times normal upper limits will exclude a patient without a re-test; a re-test for any values between normal and 1.5 times normal will be made, and if the values remain elevated above normal, the patient will be excluded), or history of significant liver disease
  • Under treatment for a medical condition requiring chronic use of systemic steroids
  • Any medical condition or medication that, in the opinion of the investigators, will interfere with the safe completion of the study or study outcomes

Group 2: (T1DM control subjects)

  • Detectable C-peptide level
  • Serum creatinine ≥1.5 mg/dL
  • Positive pregnancy test, or presently breast-feeding, or failure to follow effective contraceptive measures
  • Any history of malignancy except for adequately treated squamous or basal cell carcinoma of the skin
  • Active alcohol or substance abuse- includes cigarette smoking (must be abstinent for 6 months)
  • Baseline Hgb < 10.5 g/dL in females, or < 13 g/dL in males Baseline liver function tests outside of normal range (an initial liver function test panel with any values >1.5 times normal upper limits will exclude a patient without a re-test; a re-test for any values between normal and 1.5 times normal will be made, and if the values remain elevated above normal, the patient will be excluded), or history of significant liver disease
  • Addison's disease as determined by clinical history
  • Under treatment for a medical condition requiring chronic use of systemic steroids
  • Any medical condition or medication that, in the opinion of the investigators, will interfere with the safe completion of the study or study outcomes

Group 3: (Normal Controls)

  • FBG > 100 mg/dL
  • Serum creatinine ≥1.5 mg/dL
  • Positive pregnancy test, or presently breast-feeding, or failure to follow effective contraceptive measures
  • Any history of malignancy except for adequately treated squamous or basal cell carcinoma of the skin
  • Active alcohol or substance abuse- includes cigarette smoking (must be abstinent for 6 months)
  • Baseline Hgb < 10.5 g/dL in females, or < 13 g/dL in males
  • Baseline liver function tests outside of normal range (an initial liver function test panel with any values >1.5 times normal upper limits will exclude a patient without a re-test; a re-test for any values between normal and 1.5 times normal will be made, and if the values remain elevated above normal, the patient will be excluded), or history of significant liver disease
  • Under treatment for a medical condition requiring chronic use of systemic steroids
  • Any medical condition or medication that, in the opinion of the investigators, will interfere with the safe completion of the study or study outcomes
Both
18 Years to 49 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00575783
DK72409 (completed), R01DK072409, HIC# 0505000077
Yes
Robert Sherwin, Yale University
Yale University
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  • University of Miami
  • University of Minnesota - Clinical and Translational Science Institute
Principal Investigator: Robert Sherwin, MD Yale University
Yale University
January 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP