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

NCT ID: NCT01033500

Last Updated: 2013-05-08

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: NA
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-07-31
• Study Completion Date: 2012-12-31

Brief 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.

Detailed Description

This is a single center, open-label, non-randomized, prospective, pilot study of 8 Type 1 diabetic/uremic patients, ages 18-60 undergoing simultaneous islet-kidney transplantation. Study to include both male and/or female subjects.

We 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.

Furthermore, we anticipate an improvement in creatinine clearance and a reduction in Interstitial Fibrosis/Tubular Atrophy in the transplanted renal allograft, and a reduction of "de novo" human anti-HLA antibody and auto-antibody formation against the respective donors.

Without calcineurin inhibitors or steroids, we hypothesize that belatacept, in conjunction with sirolimus and mycophenolic acid will provide balanced immunosuppression for combined islet-kidney transplantation.

Conditions

Islets of Langerhans Transplantation; Diabetes Mellitus, Type 1; Kidney Transplantation

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

SIK

Basiliximab induction with maintenance immunosuppression consisting of belatacept, sirolimus or everolimus, and mycophenolate after simultaneous islet kidney transplantation.

Group Type: EXPERIMENTAL

Belatacept

Intervention Type: DRUG

Belatacept 10mg/kg on Days 0, 4, 14, 28, 56, and 84 post-transplant, and then 5mg/kg every 4 weeks for the duration of the study.

Interventions

Belatacept

Belatacept 10mg/kg on Days 0, 4, 14, 28, 56, and 84 post-transplant, and then 5mg/kg every 4 weeks for the duration of the study.

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

University of Wisconsin, Madison

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Luis Fernandez, MD

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin, Madison

Locations

University of Wisconsin

Madison, Wisconsin, United States

Countries

United States

Other Identifiers

H-2010-0042

Identifier Type: -

Identifier Source: org_study_id