Calcineurin Inhibitor-free, Steroid-free Immunosuppressive Regimen in Simultaneous Islet-Kidney Transplantation for Uremic Type 1 Diabetic Patients

• Status: Withdrawn
• Trial end date: 2012-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The investigators hypothesize that a calcineurin inhibitor-free, steroid-free, co-stimulatory blockade-based immunosuppressive regimen, in combination with a GLP-1 agonist, will reduce the islet mass required to achieve and sustain insulin independence following simultaneous islet-kidney transplantation.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Wisconsin, Madison
• Collaborator: Bristol-Myers Squibb
• Treatments: Abatacept; Calcineurin Inhibitors; Immunosuppressive Agents

Criteria

Inclusion Criteria:

• Subjects will include those with Type 1 Diabetes Mellitus, undergoing kidney transplantation, and:

• are closely followed by a primary care provider and/or endocrinologist for >6 months prior to enrollment in the trial

• do not have psychogenic factors which preclude therapeutic compliance

• have a fasting C-peptide of <0.2 ng/mL• have diabetes for >5 years • are between 18 and 65 years of age

• have a creatinine clearance of less than 20 mL/min

• have a body mass index of less than or equal to 28

• In the case of women of childbearing potential (WOCBP), must have a negative pregnancy test and avoid pregnancy throughout the study and 8 weeks after final dose of study drug.

• WOCBP must use two adequate methods of contraception.

• A male subject of fathering potential must use an adequate method of contraception to avoid conception throughout the study and for up to 8 weeks after the last dose of study drug to minimize the risk of pregnancy.

Exclusion Criteria:

• Untreated proliferative diabetic retinopathy

• HgbA1C >12

• creatinine clearance > 20 ml/minute

• presence of panel reactive antibodies (PRA) >20% (per CDC-based assay)

• malignancy or previous malignancy, except for adequately treated skin cancers (basal cell or squamous cell carcinoma) within the past 5 years

• sensitivity to iodine and/or shellfish (re: Iothalamate-based GFR testing)

• x-ray evidence of pulmonary infection

• active infections

• active peptic ulcer disease, gall stones, hemangioma, cirrhosis or portal hypertension

• serological evidence of HIV, HBSAg or HCV

• abnormal liver function tests (elevated AST and ALT > 2x upper limit of normal)

• anemia (hemoglobin) <9 gm/dl

• serum triglycerides >200 mg/dl

• serum cholesterol >240 mg/dl

• body mass index above 28

• unstable cardiovascular status (including positive stress echocardiography if >age 35); severe coexisting cardiac disease, myocardial infarction within the 6 months prior to enrollment in the study, left ventricular ejection fraction of <30%, or evidence of ongoing ischemia

• prostate specific antigen (PSA) >4 in males >40 years old or with family history of prostate cancer

• pregnancy or breastfeeding

• sexually-active females who are not: a) post-menopausal, b) surgically sterile, or c) not using an acceptable method of contraception (oral contraceptives, Norplant, Depo-Provera, and barrier devices are acceptable; condoms used alone are not acceptable)

• alcohol abuse, substance abuse or smoking within the previous 6 months

• insulin requirement >1.5 u/kg/day

• negative for Epstein-Barr virus by IgG determination

• history of factor V deficiency

• acute or chronic pancreatitis

• recurrent attenuated vaccine(s) within the previous 2 months

• use of an investigational agent within the past 4 weeks

• sexually active, fertile men not using effective birth control, if their partners are WOCBP

• prisoners, or subjects who are involuntarily incarcerated

• subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness

• Previous kidney transplant or previous non-renal transplant

• kidney transplant from expanded criteria donor (ECD)

• kidney cold ischemic time projected to be > 20 hours

• currently receiving immunosuppressive agents for autoimmune disease or other conditions or have comorbidities that treatment with such agents are likely during the trial

• any condition or circumstance that makes it unsafe to undergo an islet cell or kidney transplant