CIRTEN-Simultaneous Pancreas-Kidney Transplant Recipients

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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Conversion From Immediate Release Tacrolimus to Envarsus XR® in Simultaneous Pancreas-Kidney Recipients: Assessment of Functional, Safety and Quality of Life Outcomes (CIRTEN SPK)

Conditions
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Kidney Pancreas Transplantation

Intervention / Treatment
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* Drug: Envarsus XR


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: 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 2 years prior, with a history of tremors following transplantation.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Envarsus XR<br>Envarsus XR (extended release) will be administered orally, once-daily, for 6 months. | Drug: Envarsus XR<br>* The Envarsus XR® drug will be administered to study participants once daily, orally. The dosage can be 0.75 mg, 1 mg or 4 mg. The tacrolimus whole blood trough concentrations will be monitored and titrate Envarsus XR® dosage to achieve target whole blood trough concentration.<br>* Other names: tacrolimus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in patient and physician-assessed degree of tremors based on Fahn-Tolosa-Marin Tremor Rating Scale | FTM-TRS will be used as a tool for essential tremor scoring. (0: no tremor, 1: barely perceptible tremor, 2: < 2 cm, 3: 2-4 cm, and 4: > 4 cm). | Over 6 months | 
| Change in patient and physician-assessed degree of tremors based on Quality of Life in Essential Tremor (QUEST) Questionnaire | QUEST Questionnaire, a scoring tool will be used to measure the quality of life among patients with Essential Tremor. It consists of 30 items which are rated on a five-point scale (score 0-4), corresponding to the frequency (never, rarely, sometimes, frequently, always) with which tremor was perceived to affect a function or to be associated with various feelings and attitudes. A few items (e.g. 'I had to quit my job because of tremor') could only be answered at the extremes (yes/no; true/false), and these were scored either 0 or 4. | Over 6 months | 
| Scores on Quality of Life in Essential Tremor Questionnaires | Use QUEST (Quality of Life in Essential Tremor Questionnaire) scoring tool | Over 6 months | 
| Scores on Modified Transplant Symptom Occurrence and Symptom Distress Scale (MTSOSD) Questionnaire | MTSOSD Questionnaire scores will be used to assess the presence and distress of side effects associated with the use of immunosuppressive drugs after transplantation. | Over 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal function by eGFR (estimated Glomerular Filtration Rate) | Change between baseline and post-conversion as measured by eGFR | Over 6 months | 
| Renal function by serum creatinine | Change between baseline and post-conversion as measured by serum creatinine | Over 6 months | 
| Comparable or improved glycemic control as measured by mixed meal tolerance test | Change between baseline and post-conversion | Over 6 months | 
| Comparable or improved glycemic control as measured by HbA1c | Change between baseline and post-conversion | Over 6 months | 
| Tacrolimus doses and levels | Change between baseline and post-conversion | Over 6 months | 
| Mycophenolate doses and levels | Change between baseline and post-conversion | Over 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tremors