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

NCT00590876 | Completed

• 3 other identifiers: DK66108a_0304025134R37DK020495DK20495
• Study Type: observational
• Target: 36
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Diabetes Mellitus, Type 1

Keywords

Diabetes Mellitus, Type 1; Hypoglycemia; Pancreatic Islet Cell Allotransplantation

Outcome Measures

Primary Outcomes (1)

• fMRI

  0, 3, and 12 months

Study Arms (3)

1

T1DM patients with a history of severe hypoglycemia and/or hypoglycemia unawareness who have been selected based upon this history to undergo islet cell transplantation at the University of Minnesota.

2

T1DM patients (C-peptide negative) who are matched for age, gender, and duration of diabetes, who also have a history of severe hypoglycemia and/or hypoglycemia unawareness meeting the criteria for islet cell transplantation. The hemoglobin A1c for each of these subjects will fall within 1% of the islet transplant recipient to whom they are matched.

3

Nondiabetic subjects (fasting plasma glucose \< 110 mg/dl) who are matched for age and gender to the islet transplant recipient to whom they are matched.

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Patients undergoing pancreatic islet cell allotransplantation at the University of Minnesota Patients who are seen at Diabetes Clinics at Yale School of Medicine Nondiabetic, healthy subjects from New Haven and surrounding communities

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

Sponsors & Collaborators

• Yale University: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• Juvenile Diabetes Research Foundation: collaborator

Study Sites (2)

Yale University School of Medicine

New Haven, Connecticut, 06520, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Hypoglycemia

Condition Hierarchy (Ancestors)

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

Study Officials

• Robert Sherwin, M.D.

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: CNH Long Professor

Study Record Dates

• First Submitted: December 26, 2007
• First Posted: January 11, 2008
• Study Start: December 1, 2008
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: October 27, 2011

Record last verified: 2011-10

Locations

US (2)