Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01166724
Other study ID # 09-702
Secondary ID
Status Completed
Phase Phase 3
First received July 20, 2010
Last updated October 26, 2016
Start date July 2010
Est. completion date December 2014

Study information

Verified date October 2016
Source The Cleveland Clinic
Contact n/a
Is FDA regulated No
Health authority United States: Institutional Review Board
Study type Interventional

Clinical Trial Summary

The investigators hypothesize that Tacrolimus (Tac) withdrawal from a Tac, MMF and steroid based triple therapy regimen leads to long term improved/stabilized graft function (glomerular filtration rate, GFR) primarily as a consequence of halting CNI-induced fibrogenetic processes that mediate loss of functioning renal tissue. The investigators further hypothesize that the underlying fibrotic mechanism is mediated by pathophysiologic processes that promote epithelial to mesenchymal transition (EMT) (mediated by TGF- ƒÒ) and that early therapeutic intervention may reverse this process (mediated by BMP-7)4.

To address these hypotheses the investigators propose the following clinical and mechanistic aims:

The investigators will test the hypothesis that switching from Tac to SRL in a Tac based triple therapy regimen with MMF and steroids in living and or deceased donor renal transplant recipients leads to improvement in allograft structure and function at 2 years post-transplantation.

The investigators will test this hypothesis in an open label controlled trial where stable renal allograft recipients on Tac, MMF, prednisone maintenance immunosuppression will undergo renal biopsy at 3-4 months post-transplantation and will be randomized to either a) Remain on Tac, MMF and prednisone (CNI-maintenance) or b) switch the Tac to SRL and continue MMF and prednisone. The investigators will then compare biopsy derived measures of allograft fibrosis (CADI, Sirius Red, Banff Chronicity Index) and GFR in the two groups


Description:

We will test this hypothesis in an open label controlled trial where stable renal allograft recipients on Tac, MMF, prednisone maintenance immunosuppression will undergo renal biopsy at 3-4 months post-transplantation and will be randomized to either a) Remain on Tac, MMF and prednisone (CNI-maintenance) or b) switch the Tac to SRL and continue MMF and prednisone. We will then compare biopsy derived measures of allograft fibrosis (CADI, Sirius Red, Banff Chronicity Index) and GFR in the two groups


Recruitment information / eligibility

Status Completed
Enrollment 25
Est. completion date December 2014
Est. primary completion date December 2014
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility Inclusion Criteria:

1. Absence of clinical acute rejection in post-transplant period preceding randomization

2. HLA-mismatched solitary first and second kidney transplant recipients

3. Absence of any degree of rejection (Banff 2007) on renal biopsy at 3-6 months(+/- 2 months) post-transplant.

4. Absence of post-transplant donor-specific antibody

Exclusion Criteria:

1. HLA-identical transplants

2. Contraindication or inability to undergo renal biopsy, like previous complications due to biopsies, anticoagulation, active infection, etc.

3. Positive flow cross match, sensitized recipient, presence of donor-specific antibody.

4. Rejection episode after transplantation, either cellular or humoral on for cause or renal biopsy.

5. Rejection present on pre-randomization renal biopsy.

6. Proteinuria greater than 0.3 gram/day

7. Native kidney disease biopsy proven or likely glomerulonephritis, primary or recurrent FSGS, MPGN or primary or recurrent membranous GN.

8. Hypertriglyceridemia > 400 mg/dL (treated), LDL cholesterol > 160 mg/dL while on optimal treatment.

9. WBC < 2000/mm3, ANC < 1000 mm3, Platelet count < 100,000 mm3

10. Active wound issues.

11. Primary non-function.

12. Active BKV or CMV disease.

13. Evidence of recurrent disease.

14. Active infection

15. Pregnancy

16. Women of childbearing potential unable or unwilling to use birth control during the study.

17. e GFR = 40 ml/ min at screening

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Drug:
Sirolumus
Tacrolimus to Sirolimus
Tacrolimus
dosage per trough level

Locations

Country Name City State
United States Cleveland Clinic Cleveland Ohio

Sponsors (1)

Lead Sponsor Collaborator
The Cleveland Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary biopsy-derived measures of fibrosis The primary analyses will compare biopsy-derived measures of fibrosis in the Tac-maintenance and SRL groups using the t-test. 12 months No
Secondary change in iGFR We will also compare the change in iGFR (as well as estimated GFR) from time of conversion to 12 and 24 months of follow up by paired t-test between groups. 12 months No
See also
  Status Clinical Trial Phase
Completed NCT04087720 - Study of Pegloticase in Participants With Uncontrolled Gout Who Have Had a Kidney Transplant Phase 4
Completed NCT03749356 - Study to Evaluate the Efficacy and Safety of Once-Daily Tacrolimus in Kidney Transplant Recipients Phase 4
Withdrawn NCT05811468 - Study Correlation Between Blood, Tissue Gene Expression, Donor Derived Cell Free DNA and Histopathology in Kidney Transplant Recipients
Completed NCT03527238 - Optimizing Immunosuppression Drug Dosing Via Phenotypic Precision Medicine Phase 2
Completed NCT00498576 - Melatonin and Adiponectin in Hypertensive Kidney Transplant N/A
Completed NCT00642655 - Rituximab and Intravenous Immunoglobulin (IVIG) for Desensitization in Renal Transplantation Phase 1/Phase 2
Completed NCT00374400 - The Paired Donation Consortium Paired Donation Program N/A
Completed NCT01710033 - A Study Of CP-690,550 In Stable Kidney Transplant Patients Phase 1
Completed NCT00205257 - Prediction of Acute Rejection in Renal Transplant Phase 1
Completed NCT02711826 - Treg Therapy in Subclinical Inflammation in Kidney Transplantation Phase 1/Phase 2
Withdrawn NCT03978494 - Study to Compare Pharmacokinetics of Tacrolimus Prolonged-release (PR) Capsules and Advagraf® PR Capsules in Stable Kidney Transplant Patients. Phase 1
Completed NCT03837522 - Trial to Define the Benefits and Harms of Deceased Donor Kidney Procurement Biopsies N/A
Not yet recruiting NCT06025240 - Expanding the Scope of Post-transplant HLA-specific Antibody Detection and Monitoring in Renal Transplant Recipients
Completed NCT05029310 - Effects of Patiromer on Pharmacokinetics of Immunosuppresive Drugs in Renal Transplant Recipients Phase 4
Completed NCT03644485 - Clinical Outcome of Delayed or Standard Prograf Together With Induction Therapy Followed by Conversion to Advagraf in Donation After Cardiac (or Circulatory) Death (DCD) Kidney Transplant Recipients Phase 4
Active, not recruiting NCT02409901 - Effects of Personalized Physical Rehabilitation in Kidney Transplant Recipients N/A
Completed NCT01047410 - ACtive Care After Transplantation, the ACT Study N/A
Completed NCT00940940 - Safety and Immunogenicity of Zostavax Vaccine in Patients Undergoing Living Donor Kidney Transplantation Phase 4
Completed NCT00217126 - The Study of Long-term Deterioration of Kidney Transplants. Phase 4
Completed NCT00270712 - A Study of Factors That Affect Long-Term Kidney Transplant Function