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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to adjust medications for kidney transplant recipients. It uses Phenotypic Personalized Medicine Dosing to determine the optimal medicine combination to prevent organ rejection while minimizing side effects. Participants will either follow their doctor's usual dosing plan or use the Phenotypic Personalized Medicine Dosing approach. The trial seeks patients with end-stage kidney disease who have received a kidney transplant from a deceased donor and are set to take tacrolimus as part of their treatment. As an unphased trial, this study offers a unique opportunity to explore personalized medicine approaches that could enhance treatment outcomes.

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 prior data suggests that Phenotypic Personalized Medicine Dosing is safe for kidney transplant patients?

Research has shown that Phenotypic Personalized Medicine (PPM) dosing has been tested in kidney and liver transplant patients and is generally safe. One study found that PPM-guided dosing significantly reduced the number of days when drug levels deviated from the target range after liver transplants. As a result, patients maintained drug levels closer to the ideal, which is crucial for safe treatment.

By adjusting drug doses based on individual needs, PPM helps achieve effective treatment with potentially fewer side effects. This method uses information like drug levels and patient characteristics to determine the best combination and dosage of medications. Overall, this approach aims to protect the transplanted kidney while ensuring drug doses remain safe and effective. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Phenotypic Personalized Medicine (PPM) Dosing for kidney transplant rejection because it offers a tailored approach, unlike the standard practice of physician-determined dosing. While traditional methods rely on physician judgment and general guidelines, PPM uses advanced data analysis to create individualized dose-response profiles for patients. This innovative approach aims to optimize the combination of drugs like tacrolimus, MMF/MPA, and prednisone, minimizing potential kidney damage while maintaining effective medication levels. The potential for personalized dosing to improve outcomes and reduce side effects makes it a promising development in transplant care.

What evidence suggests that this trial's treatments could be effective for kidney transplant rejection?

Research shows that Phenotypic Personalized Medicine (PPM) for dosing can help manage kidney transplant rejection. In this trial, participants in the PPM Dosing arm will have their dd-cfDNA data analyzed to derive an optimal combination of tacrolimus, MMF/MPA, and prednisone, aiming to achieve minimal renal allograft injury. One study found that PPM-guided dosing helped patients maintain medication levels closer to the target, reducing the days when drug levels were too high or too low. Another study with kidney transplant patients found that those using PPM had more consistent medication levels and reached their target levels faster. This suggests that PPM could lead to better control of medication dosing, crucial for preventing rejection in kidney transplants. These findings indicate that PPM might enhance treatment effectiveness by tailoring medication plans to each patient's unique needs. ^{1 2 3 6 7}

Who Is on the Research Team?

Ali Zarrinpar, MD PhD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. withpower.com withpower.com/trial/early-phase-1-rejection-transplant-kidney-7-2022-9f92a

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

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7723319/

Recent advances in precision medicine for individualized ... One prospective study of 129 renal transplant patients, excluding those with impaired liver function and combined organ transplantation tested ANNs in ...

3. nature.com nature.com/articles/s41467-025-59739-6

Tacrolimus dosing in liver transplant recipients using ... We found that PPM-guided dosing significantly reduced the percentage of post-transplant days with large deviations from the target range, ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7967030/

Evaluating the Impact of CYP3A5 Genotype on Post ... The time to the composite outcome of BPAR or DSA did not differ significantly between CYP3A5 phenotype groups in renal transplant recipients.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0085253823004751

A prospective controlled, randomized clinical trial of kidney ... Patients receiving PPK showed significantly less intra-patient variability compared to the control group, reached the Tac Co target sooner (5 days vs 10 days), ...

6. journals.lww.com journals.lww.com/transplantationdirect/fulltext/2021/02000/precision_medicine_in_kidney_transplantation__just.3.aspx

Precision Medicine in Kidney Transplantation: Just Hype or... Desirable outcomes including rejection- and infection-free kidney transplantation are not guaranteed despite current strategies for immunosuppression and ...

7. medrxiv.org medrxiv.org/content/10.1101/2023.05.26.23290604v1.full-text

Personalized Tacrolimus Dosing After Liver Transplantation The primary outcome measure was percent days with large (>2 ng/mL) deviation from target range from transplant to discharge. Secondary outcomes ...