Islet Transplantation Using Abatacept

Inclusion Criteria

• Male and Female patients age 18 to 65 years of age
• Clinical history compatible with type 1 diabetes with onset of disease at 5 years at the time of enrollment.
• Body mass index less than or equal to 26
• 18 to 65 years of age
• Absent stimulated C-peptide ( 300 mg/24h)
• Baseline Hgb below the lower limits of normal at the local laboratory; lymphopenia ( 130 mg/dL, treated or untreated; and/or fasting triglycerides >300 mg/dL)
• Negative antibody test for Varicella zoster virus (subjects may be reconsidered if they receive the vaccination and convert to a positive antibody)
• History of malignancy (except squamous or basal cell skin carcinoma) within the previous 5 years
• Previous/concurrent organ transplantation
• Presence of HLA Panel Reactive Antibodies >20%
• Active peptic ulcer disease
• Evidence of gallbladder disease including cholecystitis and cholelithiasis
• Evidence of liver disease including: hepatic neoplasm, portal hypertension, or persistently abnormal liver function tests
• Current use of systemic steroid medications
• Evidence of insulin resistance (insulin requirements >0.8 units/kg/day)
• Inability to provide informed consent
• Severe unremitting diarrhea, vomiting or other gastrointestinal disorders potentially interfering with the ability to absorb oral medications.
• Hyperlipidemia despite medical therapy (fasting LDL cholesterol >130 mg/dL, treated or untreated; and/or fasting triglycerides >200 mg/dL).
• Acute or chronic pancreatitis.
• Symptomatic peptic ulcer disease.
• Use of any other investigational agents within 4 weeks of participation.
• Any condition or any circumstance that makes it unsafe to undergo an islet cell transplant
• Any coagulopathy or medical condition requiring long-term anticoagulant therapy (e.g., warfarin) after transplantation (low-dose aspirin treatment is allowed) or patients with an INR >1.5.
• Sickle Cell Anemia (Subjects with Sickle Cell Anemia, trait HbSS, are at high risk for complications after transplantation related to immunosuppressive therapy. These complications include stroke and sickle cell crisis. Therefore, we will exclude these subjects from our study to minimize risks to study subjects.)
• For female participants: Positive pregnancy test, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of the study and 3 months after discontinuation. For male participants: intent to procreate during the duration of the study or within 3 months after discontinuation or unwillingness to use effective measures of contraception. Oral contraceptives, Norplant®, Depo-Provera®, and barrier devices with spermicide are acceptable contraceptive methods; condoms used alone are not acceptable.
• Active alcohol or substance abuse. This includes cigarette smoking (must be abstinent for six months). Active alcohol 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 problems, such as driving under the influence of alcohol or for causing physical harm to someone while intoxicated
• Continued alcohol abuse despite having ongoing relationship problems that are caused or worsened by the effects of alcohol
• Psychiatric disorder making the subject not a suitable candidate for transplantation, e.g., schizophrenia, bipolar disorder, or major depression that is unstable or uncontrolled on current medication. (A psychological or psychiatric consultation is required only if considered necessary by some current indication or history.)