A multi-centre trial of a new immunosuppression regime for pancreatic islet transplant recipients
- Conditions
- Hypoglycaemia UnawarenessType 1 DiabetesIslet graft survivalMetabolic and Endocrine - Diabetes
- Registration Number
- ACTRN12619000268145
- Lead Sponsor
- The University of Sydney
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 15
1. Subjects must be diagnosed with type 1 diabetes for more than 5 years.
2. Subjects must, in the opinion of an endocrinologist, have severe recurrent episodes of hypoglycaemia not responsive to standard therapy.
3. Subjects must have a calculated GFR greater than or equal to 75 mL/min/1.73 m2 (MDRD formula) at the time of enrolment (based on screening/baseline central laboratory results). They must have a serum creatinine greater than or equal to 130 µmol/L and a 24 hour urine protein estimation < 300 mg/day.
4. Subjects must weigh less than 85 Kg
5. Subjects must be EBV IgG positive
6. Men and women, ages 18 years and older, inclusive
7. WOCBP must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the last dose of study drug in such a manner that the risk of pregnancy is minimized.
8. For WOCBP using MMF and MPA, two reliable forms of contraception must be used simultaneously unless abstinence is the chosen method.
1) WOCBP who are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for the entire study period and for up to 8 weeks after the last dose of study medication. It should be noted that according to the US product information for mycophenolate mofetil (CellCept©) and mycophenolic acid (Myfortic©), two reliable forms of contraception be used simultaneously unless abstinence is the chosen method”
2) WOCBP using a prohibited contraceptive method
3) Women who are pregnant or breastfeeding
4) Women with a positive pregnancy test on enrolment or prior to study drug administration
5) Subjects who had a positive T-cell or B-cell crossmatch
6) Subjects with a prior solid organ (kidney, heart, liver, pancreas) or cell ( bone marrow, stem cell) transplants
7) Subjects who are known hepatitis C antibody-positive or PCR-positive for hepatitisC (neither hepatitis C antibody or PCR for hepatitis C testing is required for entry into the study)
8) Subjects who are known hepatitis B surface antigen-positive or PCR-positive for hepatitis B (neither hepatitis B surface antigen or PCR for hepatitis B testing is required for entry into the study)
9) Subjects with known human immunodeficiency virus (HIV) infection. HIV testing is not required for entry into the study
10) Subjects with a chest radiograph (posterior-anterior and lateral views) consistent with an acute lung parenchymal process, malignancy, or active tuberculosis. Subjects must have a chest radiograph within 2 months prior to transplantation
11) Subjects with any significant infection
12) Baseline LFT's outside of normal range
13) Insulin requirement > 0.7 IU/kg/day or a HbA1c > 12%
14) Serum Cholesterol > 10 mmol/l
15) Requirement for systemic corticosteroid usage
16) Treatment with terfenadine, cisapride, astemizole, pimozide, or ketoconazole (that is not discontinued prior to sirolimus administration).
17) Malignant disease other than localized and excised skin Squamous Cell or Basal Cell Carcinoma
18) Hepatic disease, including any form of active viral hepatitis, portal venous abnormality or cirrhosis
19) Chronic Pancreatitis
20) Significant cardiac disease including ischaemic and valvular heart disease
21) Respiratory disease including clinically significant asthma, bronchiectasis or obstructive airways disease.
22) Any form of chronic or current acute mental or psychiatric illness that in the opinion of the investigator would prevent them from adhering to the trial protocol
23) Any form of chronic infection that could in the view of the investigator pose a risk after transplantation
24) Allergy to intravenous contrast agents, sirolimus, belatacept or anti-thymocyte globulin
25) Subjects whose life expectancy is severely limited by disease state or other underlying medical condition
26) Subjects with a history of cancer (other than non-melanoma skin cell cancers cured by local resection) within the last 5 years
27) Subjects with a history of substance abuse (drug or alcohol) within the past 5 years, or psychotic disorders that are not compatible with adequate study follow-up
28) Any other disease which in the opinion of the investigator may represent a significant risk after transplantation and immunosuppression
29) Subjects with laboratory values that meet the following criteria are to be excluded from the study:
30) Urine Assay:
a) Proteinuria > 300 mg/day or
b) Urine protein : creatinine ratio > 1
31) Hematology:
a) Hemoglobi
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method