Home-based Therapeutic Drug Monitoring in Kidney Transplantation

Study Overview
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Brief Summary
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This is a randomized clinical trial to assess an intervention to facilitate patient self-collection of dried blood samples at home for therapeutic drug monitoring of tacrolimus and mycophenolate in kidney transplant recipients. In this study, text messages will be sent to mobile devices to remind kidney transplant recipients to perform therapeutic drug monitoring at home using a special lancet device to collect blood samples from the upper arm. The primary objective is to evaluate if more intensive, bidirectional text messages improve the quality of sample collection.

Detailed Description
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Optimal immunosuppression therapy, most commonly with tacrolimus and mycophenolate, is critical for kidney transplantation success. While graft and patient survival are multifaceted phenomena, they are commonly attributed to chronic, subclinical immune-mediated damage, tacrolimus nephrotoxicity, or premature death secondary to complications amplified by immunosuppression such as infection, malignancy, and cardiovascular disease. New approaches are required to explore ways to optimize the precision dosing of immunosuppression to reduce the associated significant long-term side effects with the potential to improve kidney transplantation outcomes. Currently, immunosuppressant dose adjustments empirically balance efficacy and toxicity in conjunction with limited tacrolimus blood concentrations. However, both tacrolimus and mycophenolate possess interpatient variability in drug exposure and response with considerable overlap between therapeutic and adverse effects. Only tacrolimus is routinely monitored as mycophenolate trough concentration is not correlated with drug exposure or outcomes. The pharmacokinetic parameter area under the concentration-time curve (AUC) offers a greater understanding of total drug exposure and has been associated with improved outcomes for both tacrolimus and mycophenolate. Yet, AUC is not routinely determined because it is impractical due to the need for multiple repeated samples in the clinic. The investigators propose a prospective, single-center pilot study to evaluate the ability of a text messaging intervention coupled with a novel lancet device, the Tasso-M20, to facilitate the collection of dried blood samples by the patient at home for AUC estimation. The goal of the project is to develop a patient-centric strategy to allow frequent, longitudinal, minimally invasive sample collection which allows for more detailed assessments of immunosuppression exposure. The primary objective is to compare the effect of bidirectional text communication on adherence to and accuracy of home-based AUC collection versus unidirectional text reminders in kidney transplant recipients receiving tacrolimus and mycophenolate. The secondary objective is to assess the bioanalytical agreement of two sample collection methods (dried blood spot and venipuncture) as measured by Liquid Chromatography with tandem mass spectrometry (LC-MS/MS).

Official Title
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Single Center, Pilot Evaluation of Home-based Therapeutic Drug Monitoring for Tacrolimus and Mycophenolate in Kidney Transplantation

Conditions
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Kidney Transplant

Intervention / Treatment
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* Behavioral: Automated text messages


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recipient of a kidney or kidney/pancreas transplant Receiving immediate-release tacrolimus and mycophenolate mofetil Willing to received text messages with a mobile device capable of receiving messages Willing to receive standard labs at a Michigan Medicine lab draw site on 2 occasions Ability to understand, read, and speak English Ability to understand and willingness to sign written informed consent Exclusion Criteria: History of multi-organ transplant (other than pancreas) History of allergy to tape adhesives

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomized in a 1:2 allocation ratio to receive one of two text messaging interventions (basic text message reminders or more intensive bidirectional messages).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Unidirectional Text Reminders<br>Participants in the unidirectional text reminder arm will receive automated text messages to remind them to collect blood samples 48 hours before, 12 hours before, and the morning of the planned sample collection. N=15 | Behavioral: Automated text messages<br>* Automated text messages will be used to facilitate blood sample collection at home for therapeutic drug monitoring of tacrolimus and mycophenolate. Participants will collect dried blood samples on 4 occasions. Two days in the clinical with simultaneous venipuncture (one sample) and two days at home with 4 samples collected at specified time points over 8 hours.<br>|
| Experimental: Bidirectional Text Communication<br>Participants in the bidirectional text communication arm will also receive automated messages to remind them to collect blood samples 48 hours before, 12 hours before, and the morning of the planned sample collection but they will be asked to confirm the planned day or reschedule. On the day of sample collection participants will also reply with the time the samples are collected to trigger future reminder messages for each of the 4 samples. N=30 | Behavioral: Automated text messages<br>* Automated text messages will be used to facilitate blood sample collection at home for therapeutic drug monitoring of tacrolimus and mycophenolate. Participants will collect dried blood samples on 4 occasions. Two days in the clinical with simultaneous venipuncture (one sample) and two days at home with 4 samples collected at specified time points over 8 hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Successful home-based therapeutic drug monitoring | Successful home-based therapeutic drug monitoring will be defined as a binary composite of 1) timely receipt (post marked within 48 hours of planned sample collection) of samples and 2) adequate documentation of sample collection time data for pharmacokinetic analysis. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bioanalytical assay agreement for tacrolimus | Compare concentrations of tacrolimus obtained using the two sample collection methods (dried blood and venipuncture) as measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS) | 2 days | 
| Bioanalytical assay agreement for mycophenolic acid | Compare concentrations of mycophenolic acid obtained using the two sample collection methods (dried blood and venipuncture) as measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS) | 2 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tacrolimus, Mycophenolate, Therapeutic Drug Monitoring