Overview
This is a Phase II/III, Single-center, Prospective, Open-label, Single Arm Study of 30 Simultaneous Kidney Pancreas recipients who received a transplant at least 3 months, but no more than 5 years prior, with a history of tremors following transplantation.
Description
Accrual objective: Enrollment of 2-3 participants per month and all participants within an 18 month period. With minimum of 1 year follow-up post-conversion, we anticipate the entire study would be completed within 2 ½ years.
Study design: This is a Phase II/III, Single-center, Prospective, Open-label, Single Arm Study of 30 Simultaneous Kidney Pancreas recipients who received a transplant at least 3 months, but no more than 5 years prior, with a history of tremors following transplantation.
Study duration: There will be a minimum of 1 year follow-up post-conversion, and it is expected that the entire study would be completed within 2 ½ years.
Study aims:
- Determine if EnvarsusXR® reduces tremor severity compared to IR tacrolimus
- Determine if EnvarsusXR® improves renal function or glycemic control compared to IR tacrolimus
- Compare the efficacy of EnvarsusXR® by comparing the outcomes (patient, pancreas graft and kidney graft survival) of patients treated with Envarsus XR to those of contemporary and historical controls at our center treated with IR tacrolimus, with the goal of showing non-inferiority.
- Compare insulin resistance and insulin sensitivity by defined measures post conversion between T1D and T2D recipients.
Primary Endpoint:
- Improvement in patient and physician-assessed degree of tremors based on FTM (Fahn-Tolosa-Martin Tremor Rating Scale) and QUEST (Quality of Life in Essential Tremor Questionnaire) scoring tools
- Scores on Quality of Life in Essential Tremor and Modified Transplant Symptom Occurrence and Symptom Distress Scale (MTSOSD) Questionnaires
Secondary Endpoints:
- Renal function - eGFR (estimated glomerular filtration rate) and serum creatinine
- Glycemic control - AUC by MMTT, fasting BG, fasting C-peptide, calculated C-peptide/glucose ratio, calculated 20/(fasting Cpeptide x fasting BG) as a measure of insulin resistance, calculated HOMA-IR (fasting insulin x fasting BG)/22.5 as a measure of insulin sensitivity/resistance, calculated BETA-2 score to sensitive estimate beta cell function, and HbA1c.
- Tacrolimus and Mycophenolate doses as well as TAC and MPA levels
Eligibility
Inclusion Criteria:
- Adult, 18-70 years of age
- Participant must be able to understand and provide consent
- History of Diabetes Type 1 or Insulin-Dependent Diabetes Type 2 with Chronic Kidney Disease (CKD)
- Recipient of a Simultaneous Pancreas Kidney (SPK) transplant, 3- 60 months prior to screening, per Principal Investigator's discretion.
- Have a history of tremors following transplantation
- Stable pancreas allograft function as evidenced by no requirement of exogenous insulin or oral anti-diabetic agents and stable pancreatic enzymes
- Stable kidney allograft function
- Currently taking Immediate-Release (IR) tacrolimus
- Women of child-bearing potential (WOCP) must have a negative pregnancy test at the time of study entry
Exclusion Criteria:
- Currently maintained on an extended-release tacrolimus immunosuppressive regimen
- Previous history of tremors prior to transplantation
- Solitary pancreas transplant recipients
- History of solid organ transplant other than a kidney or pancreas
- Uncontrolled concomitant infection at the discretion of the investigator
- Presence of Donor Specific Antibodies