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

Diabetes Mellitus, Type 1 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01033500
• Other study ID #: H-2010-0042
• Status: Withdrawn
• Phase: N/A
• First received: December 15, 2009
• Last updated: May 6, 2013
• Start date: July 2010
• Est. completion date: December 2012

Study information

• Verified date: May 2013
• Source: University of Wisconsin, Madison
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
United States	University of Wisconsin	Madison	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
University of Wisconsin, Madison	Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Achieve and consistently maintain insulin independence in simultaneous islet-kidney transplant recipients for one year.		1 year	No