The Impact of Pancreatic Islet Cell Allotransplantation on Cognitive Function in Type 1 Diabetes Mellitus

Completed

Conditions studied: Diabetes Mellitus, Type 1

In brief

In patients with Type 1 Diabetes Mellitus, hypoglycemia (low blood sugar) is the rate-limiting step to achieve glucose level control. As a result, understanding the body's responses (including the brain's response) to hypoglycemia is essential for the effective treatment of patients with T1DM. The purpose of this research is to determine whether pancreatic islet cell allotransplantation to restore normoglycemia (normal blood glucose levels) in Type 1 Diabetic patients with hypoglycemia unawareness alters brain fuel utilization and cognitive performance under euglycemic (blood sugar at 100 mg/dl) and hypoglycemic (blood sugar at 50 mg/dl) conditions. Three groups of subjects will be studied: (1) T1DM patients with a history of severe hypoglycemia and/or hypoglycemia unawareness who have been selected for pancreatic islet cell allotransplantation; (2) T1DM patients who also have a history of severe hypoglycemia and/or hypoglycemia unawareness; (3) nondiabetic subjects. All subjects will undergo identical testing including: (a) screening; (b) neuropsychological testing; (c) and functional magnetic resonance imaging (fMRI) during euglycemic and hypoglycemic conditions.

Key facts

Study ID

NCT00590876

Run by

Yale University

People needed

36

Starts

2008-12-01

Expected to finish

2011-07-01

Last updated by the study team

2011-10-27

Who can join

Age: 18 and older, up to 55. Sex: any. Healthy volunteers: accepted.

You may qualify if…

• T1DM subjects must be 18 years or older and able to provide written consent
• T1DM subjects must be undergoing intensive management, defined by self-monitoring of glucose values 3 or more times each day and by the administration of 3 or more insulin injections each day (or the use of insulin pump therapy). This clinical management must be monitored in close cooperation with an endocrinologist as defined by at least 3 contacts during the previous 12 months.
• T1DM subjects must demonstrate at least one of the following situations that persist despite intensive insulin management efforts:
• metabolic lability/instability, characterized by either 2 or more episodes of severe hypoglycemia within one year (defined as an event with symptoms consistent with hypoglycemia in which the patient requires the assistance of another person, and which is associated with a blood glucose of < 50 mg/dl or prompt recovery after administration of oral carbohydrate, intravenous glucose, or glucagon) or 2 or more hospital admissions for diabetic ketoacidosis over the last year.
• reduced awareness of hypoglycemia (defined by a specific hypoglycemia questionnaire)

You may not qualify if…

• Age < 18 years
• Body weight > 75 kg at screening
• BMI > 24 (female) and > 25 (male) kg/m2
• Waist to hip ratio greater than or equal to 0.80 (female) and greater than or equal to 0.95 (male)
• Insulin requirement of > 0.7IU/kg/day or > 50 IU per day, whichever is less
• Positive C-peptide response to intravenous arginine stimulation (5g): any C-peptide greater than or equal to 0.2ng/ml at 2, 3, 4, 5, 7, and 10 minutes post infusion
• Untreated proliferative retinopathy
• Creatinine clearance < 75ml/min/1.73 m2
• Serum creatinine greater than or equal to 1.3 mg/dl for females, and greater than or equal to 1.5 mg/dl for males
• Previous pancreas or islet cell transplant
• Presence of history of panel-reactive anti-HLA antibodies > 10%
• Positive pregnancy test or presently breast-feeding, or failure to follow effective contraceptive measures or abstinence (oral contraceptives, Norplant, Depo-Provera, and barrier devices are acceptable; condom use alone is not acceptable.)
• Active infection including Hepatitis C, Hepatitis B, HIV, or Tuberculosis (or under treatment for suspected Tuberculosis)
• Negative screen for Epstein-Barr Virus (EBV) or by an EBNA method
• Invasive aspergillus infection within a year prior to study entry
• Any history of malignancy except for adequately treated squamous cell or basal cell carcinoma of the skin
• Active alcohol or substance abuse which includes cigarette smoking (must be abstinent for 6 months). Active alcohol use abuse should be considered using the current NIAAA definitions whereby alcohol abuse is defined by a pattern of drinking that is accompanied by one or more of the following situations within a 12-month period:
• Failure to fulfill major work, school, or home responsibilities
• Drinking in situations that are physically dangerous, such as while driving a car or operating machinery
• Recurring alcohol-related legal problem, such as being arrested for driving under the influence of alcohol or for physically hurting someone while drunk
• Continued drinking despite having ongoing relationship problems that are caused or worsened by the effects of alcohol
• History of nonadherence to prescribed regimens
• Psychiatric disorder making the subject not a suitable candidate for transplantation (for those who are undergoing islet cell allotransplantation).
• Inability to provide informed consent
• Baseline Hgb < 11.7 g/dl in females, or < 13 g/dl in males; lymphopenia (< 1 ,000 lymphocytes/mcl) or leukopenia (< 3,000 total leukocytes/mcl), or an absolute CD4 count < 500, or platelets < 150,000

Where it is running

• Yale University School of Medicine — New Haven, Connecticut, United States
• University of Minnesota — Minneapolis, Minnesota, United States

Full record on ClinicalTrials.gov

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