CIRTEN-Simultaneous Pancreas-Kidney Transplant Recipients

Official title

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

Overview

This is a Phase II/III, Single-center, Prospective, Open-label, Single Arm Study of 20 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

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 20 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:

1. 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 2. Scores on Quality of Life in Essential Tremor and Modified Transplant Symptom Occurrence and Symptom Distress Scale (MTSOSD) Questionnaires

Secondary Endpoints:

1. Renal function - eGFR (estimated glomerular filtration rate) and serum creatinine 2. 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. 3. Tacrolimus and Mycophenolate doses as well as TAC and MPA levels

Interventions

• Drug Envarsus XR
  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.

Primary outcome measures

• Change in patient and physician-assessed degree of tremors based on Fahn-Tolosa-Marin Tremor Rating Scale [Time frame: Over 6 months]
• Change in patient and physician-assessed degree of tremors based on Quality of Life in Essential Tremor (QUEST) Questionnaire [Time frame: Over 6 months]
• Scores on Quality of Life in Essential Tremor Questionnaires [Time frame: Over 6 months]
• Scores on Modified Transplant Symptom Occurrence and Symptom Distress Scale (MTSOSD) Questionnaire [Time frame: Over 6 months]

Secondary outcome measures (6)

• Renal function by eGFR (estimated Glomerular Filtration Rate) [Time frame: Over 6 months]
• Renal function by serum creatinine [Time frame: Over 6 months]
• Comparable or improved glycemic control as measured by mixed meal tolerance test [Time frame: Over 6 months]
• Comparable or improved glycemic control as measured by HbA1c [Time frame: Over 6 months]
• Tacrolimus doses and levels [Time frame: Over 6 months]
• Mycophenolate doses and levels [Time frame: Over 6 months]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• University of Wisconsin — Madison

Publications

• Langone A, Steinberg SM, Gedaly R, Chan LK, Shah T, Sethi KD, Nigro V, Morgan JC; STRATO Investigators. Switching STudy of Kidney TRansplant PAtients with Tremor to LCP-TacrO (STRATO): an open-label, multicenter, prospective phase 3b study. Clin Transplant. 2015 Sep;29(9):796-805. doi: 10.1111/ctr.12581. Epub 2015 Aug 6. PMID 26113208
• Baraldo M. Meltdose Tacrolimus Pharmacokinetics. Transplant Proc. 2016 Mar;48(2):420-3. doi: 10.1016/j.transproceed.2016.02.002. PMID 27109969
• Kerstenetzky L, Descourouez JL, Jorgenson MR, Felix DC, Mandelbrot DA, Redfield RR, Odorico JS. A Single-Center Experience With Tacrolimus LCP (Envarsus XR) in Pancreas Transplant Recipients. Ann Pharmacother. 2018 Apr;52(4):392-396. doi: 10.1177/1060028017749076. Epub 2017 Dec 14. No abstract available. PMID 29241340
• Stacy MA, Elble RJ, Ondo WG, Wu SC, Hulihan J; TRS study group. Assessment of interrater and intrarater reliability of the Fahn-Tolosa-Marin Tremor Rating Scale in essential tremor. Mov Disord. 2007 Apr 30;22(6):833-8. doi: 10.1002/mds.21412. PMID 17343274
• Ohkura T, Shiochi H, Fujioka Y, Sumi K, Yamamoto N, Matsuzawa K, Izawa S, Kinoshita H, Ohkura H, Kato M, Taniguchi S, Yamamoto K. 20/(fasting C-peptide x fasting plasma glucose) is a simple and effective index of insulin resistance in patients with type 2 diabetes mellitus: a preliminary report. Cardiovasc Diabetol. 2013 Jan 22;12:21. doi: 10.1186/1475-2840-12-21. PMID 23339473
• Gutch M, Kumar S, Razi SM, Gupta KK, Gupta A. Assessment of insulin sensitivity/resistance. Indian J Endocrinol Metab. 2015 Jan-Feb;19(1):160-4. doi: 10.4103/2230-8210.146874. PMID 25593845
• Forbes S, Oram RA, Smith A, Lam A, Olateju T, Imes S, Malcolm AJ, Shapiro AM, Senior PA. Validation of the BETA-2 Score: An Improved Tool to Estimate Beta Cell Function After Clinical Islet Transplantation Using a Single Fasting Blood Sample. Am J Transplant. 2016 Sep;16(9):2704-13. doi: 10.1111/ajt.13807. Epub 2016 Apr 21. PMID 27017888

Identifiers

NCT: NCT03769298 · 2018-0821 · A539742 · SMPH/SURGERY/TRANSPLANT · Protocol Version 3/10/2025

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗