Effect of Tacrolimus Formulation on Neurological Side Effects in Older Kidney Transplant Recipients

Phase 4

Completed

• Conditions: Kidney Transplant; Complications; Toxicity; Drug Toxicity; Neurotoxicity
• Interventions: Drug: IR Tacrolimus; Drug: Envarsus

• Registration Number: NCT03461445
• Lead Sponsor: University of California, Davis

Brief Summary

Previous studies have shown that elderly patients experience higher trough levels of tacrolimus and are more sensitive to the effects of medications, they experience higher occurrence and severity of such medication related toxicities. Therefore, the investigators hypothesize that by transitioning patients from tacrolimus immediate release to Envarsus ®, the peak-dose effect will be eliminated or attenuated, leading to a significant decrease in neurocognitive toxicities in the older patient population.

Detailed Description

The investigators will conduct a single-center, prospective, open-label, randomized study to evaluate the difference in neurocognitive side effects between Envarsus and immediate release tacrolimus. Eligible patients will be enrolled within 8 weeks post-transplantation. They will be administered a baseline panel of neurocognitive tests. They will then be randomized to either continue on immediate release tacrolimus or Envarsus. 6 weeks after randomization, the neurocognitive tests will be repeated.

Study Timeline

• Study First Submitted: 2018-03-05
• Study First Submitted QC: 2018-03-05
• Study First Posted: 2018-03-12
• Study Start: 2018-04-01
• Primary Completion: 2023-07-31
• Study Completion: 2023-07-31
• Results First Submitted: 2024-08-01
• Status Verified: 2025-04
• Results First Submitted QC: 2025-04-04
• Last Update Submitted: 2025-04-04
• Results First Posted: 2025-04-08
• Last Update Posted: 2025-04-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 64

Inclusion Criteria

1. Recipient of a kidney transplant
2. Age 60 or greater at the time of transplant
3. Kidney graft is functional (not dialysis dependent) by 4 weeks post-transplant
4. Have IR tacrolimus as maintenance therapy
5. Have BMI < 35 at time of transplant
6. Achieve therapeutic tacrolimus level within 4 weeks post-transplant

Exclusion Criteria

1. Recipient of a simultaneous non-kidney transplant (pancreas)
2. Had an episode of rejection before study enrollment
3. Had a TIA/CVA after transplantation and before study enrollment
4. Had a neurologic injury after transplantation and before study enrollment
5. Blindness
6. Have an mTOR inhibitor as maintenance therapy
7. Nonadherence, as determined by a trough level less than 7 ng/mL after achieving therapeutic level with no other rationale for sub-therapeutic levels.
8. Adults unable to consent
9. Pregnant women
10. Prisoners

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Immediate Release Tacrolimus	IR Tacrolimus	Patients will receive immediate release tacrolimus
Envarsus	Envarsus	Patients will be converted to Envarsus formulation of tacrolimus

Primary Outcome Measures

Name	Time	Method
Change in Neurocognitive Side Effects	6 weeks after randomization and baseline testing	Change in MOCA (Montreal Cognitive Assessment) from baseline to study end. MOCA scale runs from 0 to 30 with higher being a better outcome.; Change in DSST (Digital Symbol Substitution Test) from baseline to study end. DSST scale runs from 1 to 125 with higher being a better outcome.

Secondary Outcome Measures

Name	Time	Method
Change in Self-reported Side Effects	6 weeks after randomization and baseline testing	Quality of life in Essential Tremor questionnaire (QUEST) Summary Score: A 30-item scale assessing the impact of tremor on various domains of quality of life, such as communication, work and hobbies. In the QUEST questionnaire scale, a lower score is indicative of better quality of life while higher scores indicate poorer quality of life. The score is a percentage ranging from zero to 100.
Kidney Graft Survival	6 months after transplant	Number of kidney grafts still functioning at the end of the study
Patient Survival	6 months after transplant	Number patients who survived during the study

Trial Locations

Locations (1)

UC Davis; 🇺🇸 Sacramento, California, United States