Home-based Therapeutic Drug Monitoring in Kidney Transplantation

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

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.

Study Overview

• Status: Completed
• Conditions: Kidney Transplant
• Intervention / Treatment: Behavioral: Automated text messages

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Unidirectional Text Reminders; 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; 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.
Experimental: Bidirectional Text Communication; 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Samples Successfully Returned for Drug Monitoring by Participants in the Unidirectional and Bidirectional Arms	Successful home-based therapeutic drug monitoring is defined as a binary composite of 1) timely receipt (postmarked within 48 hours of planned sample collection) of samples and 2) adequate documentation of sample collection time data for pharmacokinetic analysis. Each participant in the Unidirectional and Bidirectional Text Communication arms had two opportunities for sample collection. Participants in the third arm for bioanalytical validation did not complete home sample collection and do not have results for this outcome measure.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Paired Samples With </=15% Difference Between Tacrolimus Concentrations Obtained Via Dried Blood and Venipuncture in the Analytical Validation Arm	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). Each participant in the analytical validation arm provided two sets of paired samples on different days.	2 days
Percent of Paired Samples With </=15% Difference Between Mycophenolic Acid Concentrations Obtained Via Dried Blood and Venipuncture in the Analytical Validation Arm	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). Each participant in the analytical validation arm provided two sets of paired samples on different days.	2 days

Collaborators and Investigators

• Sponsor: University of Michigan

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2022
• Primary Completion (Actual): May 6, 2024
• Study Completion (Actual): May 8, 2024

Study Registration Dates

• First Submitted: August 6, 2021
• First Submitted That Met QC Criteria: August 12, 2021
• First Posted (Actual): August 13, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 24, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Tacrolimus; Therapeutic Drug Monitoring; Mycophenolate
• Other Study ID Numbers: HUM00198148

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No