Personalized Medicine Dosing for Kidney Transplant Rejection

(AIIM Trial)

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Florida

Must be taking: Tacrolimus

Disqualifiers: Other organ transplant, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 15

Duration: 12 months

34 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, since the trial involves optimizing drug therapy, it's possible that changes to your medication regimen might be required. It's best to discuss this with the trial coordinators.

What data supports the effectiveness of the drug Phenotypic Personalized Medicine Dosing for kidney transplant rejection?

Research shows that personalized dosing methods, like the parabolic personalized dosing (PPD) platform, help keep drug levels within target ranges, reducing the risk of rejection and adverse events in transplant patients. This approach has been effective in managing drugs like tacrolimus, which is similar to the treatment being studied. ^{1 2 3 4 5}

Is personalized medicine dosing for kidney transplant rejection safe for humans?

Research on personalized medicine dosing, particularly with tacrolimus, suggests it can help maintain drug levels within safe ranges, potentially reducing adverse effects. This approach has been studied in both kidney and liver transplant patients, indicating it may be generally safe for human use. ^{1 3 5 6 7}

How is Phenotypic Personalized Medicine Dosing different from other kidney transplant rejection treatments?

Phenotypic Personalized Medicine Dosing is unique because it uses a personalized approach to determine the optimal dose of immunosuppressive drugs like tacrolimus, based on individual patient data. This method aims to maintain drug levels within a target range more effectively than standard physician-guided dosing, potentially reducing the risk of rejection and adverse effects. ^{1 3 5 7 8}

What is the purpose of this trial?

The objective of the proposed study it to perform a pilot clinical trial both to establish feasibility of applying a computational, augmented intelligence based approach, Phenotypic Precision Medicine (PPM), to optimizing combination drug therapy and to gather preliminary data to support a larger fully powered multi-center clinical trial. The key rationale for this clinical selection is that we have the technical, biological, and medical expertise in this disease, a wealth of experience in the use of PPM in both in vitro and the clinical setting, and a robust and integrated transplant program with a well-functioning clinical trial infrastructure.

Research Team

Ali Zarrinpar, MD PhD

Principal Investigator

University of Florida

Eligibility Criteria

This trial is for adults over 18 with end-stage renal disease who have received a kidney transplant and need tacrolimus immunosuppression. They must be able to consent and follow up at the center for 15 months. It's not for those intolerant to tacrolimus, with certain donor mismatches, multiple transplants, high antibody levels, incompatible blood types, specific kidney diseases on biopsy, prior bone marrow transplant or pregnancy.

Inclusion Criteria

Willing and able to provide written informed consent to participate

I need tacrolimus as my main immune system suppressant.

I am an adult with end-stage kidney disease.

Exclusion Criteria

I received a transplant from my identical twin.

My biopsy from 3 months ago shows I have lupus affecting my kidneys.

Recipient of third or more transplant

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Monitoring

Subjects without biopsy proven rejection are enrolled in the baseline monitoring period, including weekly dd-cfDNA measurements up to three months after transplantation.

3 months

Weekly visits for dd-cfDNA measurements

Treatment

Subjects are randomized into control or treatment arms. Control arm continues SOC, while treatment arm uses PPM to optimize immunosuppression regimen.

12 months

Regular SOC visits and dd-cfDNA labs as needed

Follow-up

Participants are monitored for safety and effectiveness after treatment, including a protocol biopsy at 15 months.

3 months

Final protocol biopsy at 15 months

Treatment Details

Interventions

• Phenotypic Personalized Medicine Dosing

Trial Overview The AIIM Trial tests a computational method called Phenotypic Personalized Medicine Dosing to optimize drug therapy in kidney transplant patients. This pilot study aims to prove it's feasible and gather data for a larger trial by using this approach specifically with tacrolimus dosing.

Participant Groups

Group I: PPM Dosing Experimental Treatment 1 Intervention

Subjects will have dd-cfDNA data analyzed by PPM. Data, such as drug levels and regimens, will be used to fit a 2nd order polynomial for each patient to build patient-specific dose-response profiles with covariates that include the administered drugs tacrolimus, steroids, and MMF/MPA. PPM will be used to derive an optimal combination of tacrolimus, MMF/MPA, and prednisone to achieve minimal renal allograft injury, while staying within the therapeutic range of the medications. All else being equal, the most efficacious combination with the lowest dose of tacrolimus will be utilized.

Group II: Physician Dosing Active Control 2 Interventions

Subjects will continue per SOC, where the management of their immunosuppression regimen will be determined by their physician per center practices, including dd-cfDNA data.

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

References

1. United States pubmed.ncbi.nlm.nih.gov

Lower variability of tacrolimus trough concentration after conversion from prograf to advagraf in stable kidney transplant recipients. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Computer-assisted cyclosporine dosing performs better than traditional dosing in renal transplant recipients: results of a pilot study. [2013]

3. United States pubmed.ncbi.nlm.nih.gov

A first small step toward personalized immunosuppression. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Experience with therapeutic drug monitoring of cyclosporine. [2013]

5. United States pubmed.ncbi.nlm.nih.gov

Individualizing liver transplant immunosuppression using a phenotypic personalized medicine platform. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Minimization vs tailoring: Where do we stand with personalized immunosuppression during renal transplantation in 2015? [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Personalized Tacrolimus Dosing After Liver Transplantation: A Randomized Clinical Trial. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Optimisation of immunosuppressive therapy using pharmacokinetic principles. [2018]