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Prevention of de Novo Allosensitization in Islet Transplant Recipients Following Complete Graft Loss

Prevention of de Novo Allosensitization in Islet Transplant Recipients Following Complete Graft Loss

Recruiting
18-70 years
All
Phase N/A

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Overview

This is a single-center, prospective, open label study in islet transplant recipients after complete islet graft rejection/loss, defined as stimulated c-peptide ≤0.3 ng/mL.

Description

After complete islet graft loss is determined, patient's maintenance immunosuppression (i.e. sirolimus and tacrolimus) will be discontinued and they will be placed on Myfortic® monotherapy for 2 years thereafter. After completion of two years of Myfortic® maintenance monotherapy, it will be weaned and subjects will be monitored over the subsequent twelve months, for the appearance of sensitization using panel reactive antibody (PRA) levels.

Eligibility

Inclusion Criteria:

  1. Male and female patients age 18-70 years of age.
  2. Ability to provide written informed consent.
  3. Mentally stable and able to comply with the procedures of the study protocol.
  4. Any subject currently prescribed immunosuppressive medications or discontinuation of immunosuppressive medications indicated as per current protocol of islet transplantation.
  5. History of at least one islet transplant.
  6. Stimulated C-peptide <0.3 ng/ml.

Exclusion Criteria:

  1. Known history of untreated severe hyperlipidemia, obesity, or refractory hypertension
  2. For female participants: Positive pregnancy test or presently breast-feeding.
  3. History of active infection including hepatitis B, hepatitis C, HIV, or TB.
  4. Any history of malignancy except for completely resected squamous or basal skin cell carcinoma.
  5. Known active alcohol or substance abuse.
  6. Severe co-existing history of cardiac disease, characterized by a history of any one of these conditions: recent myocardial infarction (within past 6 months), evidence of ischemia on functional cardiac exam within the last year, or left ventricular ejection fraction <30%.
  7. History of persistent elevation of liver function tests. SGOT (AST), SGPT (ALT), alkaline phosphatase or total bilirubin, with values >1.5 times normal upper limits will exclude a patient.
  8. Evidence of inter-current infection.
  9. Active peptic ulcer disease
  10. History on non-adherence to prescribed regimens including immunosuppression.
  11. PRA ≥ 50% or evidence of significant sensitization to be determined at discretion of the investigator.

Study details
    Type 1 Diabetes Mellitus

NCT01999361

Rodolfo Alejandro

18 February 2024

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