AIIM Trial: Personalized Medicine Approach to Kidney Allograft Function

NCT05432765 | Not Yet Recruiting DMC

• 1 other identifier: IRB202201106
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Kidney Transplant Rejection

Keywords

Kidney; Transplant; dd-cf DNA; Personalized Medicine

Outcome Measures

Primary Outcomes (1)

• Change in renal allograft interstitial fibrosis (IF) between 3-month baseline up to 15-month follow-up.

  Multiple studies have used this outcome because it 1) correlates well with renal function as measured by Creatinine Clearance (CrCl), 2) is a quantitative, continuous, and objective measure, thus needing fewer subjects to show a difference between groups in a small study, and 3) it is less susceptible to acute fluctuations than CrCl and more reflective of chronic injury. Renal allograft IF is a continuous variable that ranges from 0 to 100%.

  Change from 3-month baseline to 15-month follow-up

Secondary Outcomes (4)

• Change in Creatinine Clearance

  Change from 3-month baseline to 15-month follow-up

• Change in tubular atrophy and vacuolization on biopsy

  Change from 3-month baseline to 15-month follow-up

• 24-hour proteinuria

  Change from 3-month baseline to 15-month follow-up

• Cumulative tacrolimus exposure

  At 15-month follow-up

Study Arms (2)

Physician Dosing

ACTIVE COMPARATOR

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.

Other: Standard of Care Dosing

PPM Dosing

EXPERIMENTAL

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.

Other: Phenotypic Personalized Medicine Dosing

Interventions

Phenotypic Personalized Medicine Dosing OTHER

Phenotypic Personalized Medicine (PPM) will mediate mechanism-independent and patient specific optimization of immunosuppression. We have developed a powerful platform that allows the provider to use clinical data to construct a Parabolic Response Surface (PRS). Using this visualization of the data, the provider can them make a decision on the optimal combination of drug doses needed to achieve the desired outcome.

PPM Dosing

Standard of Care Dosing OTHER

Providers will decide on the combination of drug doses needed based on their overall assessment per standard of care.

Physician Dosing

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult (18 years of age or older) patients with end-stage renal disease (ESRD)
• Recipient of a first or subsequent deceased donor kidney transplant
• Clinical indication to receive tacrolimus as the primary immunosuppression
• Willing and able to provide written informed consent to participate

You may not qualify if:

• Recipients of transplanted organs other than kidney
• Recipients of a transplant from a monozygotic (identical) sibling
• Human Leukocyte Antigen (HLA)-identical donor (zero out of six antigen mismatch donor)
• Recipient of third or more transplant
• Current or historical panel reactive antibodies of more than 50%
• Blood Type (ABO) incompatibility or known moderate or strong donor specific antibodies
• De novo or recurrent glomerulonephritis on 3-month biopsy
• Lupus nephritis on 3-month biopsy
• Focal segmental glomerulosclerosis on 3-month biopsy
• BK polyomavirus nephropathy in current or prior transplant
• Recipient of a bone marrow transplant
• Recipient who is pregnant
• Enrollment in a competing trial that would interfere with selection or alteration of immunosuppression
• Inability to follow up with transplant center for up to 15 months after transplantation
• Anticipated major surgery during the time of planned study

Sponsors & Collaborators

• University of Florida: lead

Study Sites (1)

University of Florida Health Shands

Gainesville, Florida, 32610, United States

Location

Related Publications (10)

• Zarrinpar A, Busuttil RW. Liver transplantation: past, present and future. Nat Rev Gastroenterol Hepatol. 2013 Jul;10(7):434-40. doi: 10.1038/nrgastro.2013.88. Epub 2013 Jun 11.

  PMID: 23752825 RESULT

• Starzl TE, Iwatsuki S, Shaw BW Jr, Gordon RD, Esquivel CO. Immunosuppression and other nonsurgical factors in the improved results of liver transplantation. Semin Liver Dis. 1985 Nov;5(4):334-43. doi: 10.1055/s-2008-1040630.

  PMID: 3909427 RESULT

• Tanzi MG, Undre N, Keirns J, Fitzsimmons WE, Brown M, First MR. Pharmacokinetics of prolonged-release tacrolimus and implications for use in solid organ transplant recipients. Clin Transplant. 2016 Aug;30(8):901-11. doi: 10.1111/ctr.12763. Epub 2016 Jun 18.

  PMID: 27220013 RESULT

• Marcen R. Immunosuppressive drugs in kidney transplantation: impact on patient survival, and incidence of cardiovascular disease, malignancy and infection. Drugs. 2009 Nov 12;69(16):2227-43. doi: 10.2165/11319260-000000000-00000.

  PMID: 19852526 RESULT

• Williams D, Haragsim L. Calcineurin nephrotoxicity. Adv Chronic Kidney Dis. 2006 Jan;13(1):47-55. doi: 10.1053/j.ackd.2005.11.001.

  PMID: 16412970 RESULT

• di Paolo S, Teutonico A, Stallone G, Infante B, Schena A, Grandaliano G, Battaglia M, Ditonno P, Schena PF. Cyclosporin exposure correlates with 1 year graft function and histological damage in renal transplanted patients. Nephrol Dial Transplant. 2004 Aug;19(8):2107-12. doi: 10.1093/ndt/gfh344. Epub 2004 Jun 8.

  PMID: 15187199 RESULT

• Fortin MC, Raymond MA, Madore F, Fugere JA, Paquet M, St-Louis G, Hebert MJ. Increased risk of thrombotic microangiopathy in patients receiving a cyclosporin-sirolimus combination. Am J Transplant. 2004 Jun;4(6):946-52. doi: 10.1111/j.1600-6143.2004.00428.x.

  PMID: 15147429 RESULT

• U.S. Multicenter FK506 Liver Study Group. A comparison of tacrolimus (FK 506) and cyclosporine for immunosuppression in liver transplantation. N Engl J Med. 1994 Oct 27;331(17):1110-5. doi: 10.1056/NEJM199410273311702.

  PMID: 7523946 RESULT

• Ekberg H, Grinyo J, Nashan B, Vanrenterghem Y, Vincenti F, Voulgari A, Truman M, Nasmyth-Miller C, Rashford M. Cyclosporine sparing with mycophenolate mofetil, daclizumab and corticosteroids in renal allograft recipients: the CAESAR Study. Am J Transplant. 2007 Mar;7(3):560-70. doi: 10.1111/j.1600-6143.2006.01645.x. Epub 2007 Jan 22.

  PMID: 17229079 RESULT

• Ekberg H, Bernasconi C, Tedesco-Silva H, Vitko S, Hugo C, Demirbas A, Acevedo RR, Grinyo J, Frei U, Vanrenterghem Y, Daloze P, Halloran P. Calcineurin inhibitor minimization in the Symphony study: observational results 3 years after transplantation. Am J Transplant. 2009 Aug;9(8):1876-85. doi: 10.1111/j.1600-6143.2009.02726.x. Epub 2009 Jun 26.

  PMID: 19563339 RESULT

Study Officials

• Ali Zarrinpar, MD PhD

  University of Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Patients who meet eligibility criteria will be randomized (1:1) into one of two treatment arms using balanced-permuted block randomization with a block size of 4, stratified by transplant number (first versus second). The random allocation sequence will be prepared by the study statistician and implemented automatically by the randomization procedure in REDCap
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2022
• First Posted: June 27, 2022
• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): August 12, 2030
• Study Completion (Estimated): January 1, 2031
• Last Updated: February 10, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)