Calcineurin Inhibitor-free, Steroid-free Immunosuppressive Regimen in Simultaneous Islet-Kidney Transplantation for Uremic Type 1 Diabetic Patients
Trial Snapshot
- Phase
- Not Applicable
- Status
- Withdrawn
- Locations
- 1
- Primary Endpoint
- Achieve and consistently maintain insulin independence in simultaneous islet-kidney transplant recipients for one year.
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
SIK
Basiliximab induction with maintenance immunosuppression consisting of belatacept, sirolimus or everolimus, and mycophenolate after simultaneous islet kidney transplantation.
Intervention: Belatacept (Drug)
Outcomes
Primary Outcomes
Achieve and consistently maintain insulin independence in simultaneous islet-kidney transplant recipients for one year.
Time Frame: 1 year
Secondary Outcomes
No secondary outcomes reported