Drug Toxicity, Kidney Transplant; Complications, Neurotoxicity, Toxicity
Conditions
Keywords
Elderly, Neurotoxicity, Calcineurin inhibitors, Tacrolimus
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.
Interventions
DRUGEnvarsus
Patients will be randomized to receiving Envarsus instead of IR Tacrolimus
DRUGIR Tacrolimus
Patients will be randomized to receiving IR Tacrolimus instead of Envarsus
Sponsors
Veloxis Pharmaceuticals
University of California, Davis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Immediate Release Tacrolimus Patients will receive immediate release tacrolimus
IR Tacrolimus: Patients will be randomized to receiving IR Tacrolimus instead of Envarsus | 32 |
| Envarsus Patients will be converted to Envarsus formulation of tacrolimus
Envarsus: Patients will be randomized to receiving Envarsus instead of IR Tacrolimus | 32 |
| Total | 64 |
Baseline characteristics
| Characteristic | Immediate Release Tacrolimus | Envarsus | Total |
|---|---|---|---|
| Age, Continuous | 69 years STANDARD_DEVIATION 5.4 | 69 years STANDARD_DEVIATION 4.2 | 69 years STANDARD_DEVIATION 4.8 |
| Race/Ethnicity, Customized Asian | 4 Participants | 6 Participants | 10 Participants |
| Race/Ethnicity, Customized Black | 0 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized Hispanic | 12 Participants | 7 Participants | 19 Participants |
| Race/Ethnicity, Customized Multi-racial | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian / Pacific Islander | 0 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized Unknown/Other | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 15 Participants | 10 Participants | 25 Participants |
| Sex: Female, Male Female | 12 Participants | 12 Participants | 24 Participants |
| Sex: Female, Male Male | 20 Participants | 20 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 32 |
| other Total, other adverse events | 0 / 32 | 0 / 32 |
| serious Total, serious adverse events | 0 / 32 | 2 / 32 |
Outcome results
Primary
Change in Neurocognitive Side Effects
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.
Time frame: 6 weeks after randomization and baseline testing
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Immediate Release Tacrolimus | Change in Neurocognitive Side Effects | MOCA score difference | 1.2 score on a scale | Standard Deviation 2.1 |
| Immediate Release Tacrolimus | Change in Neurocognitive Side Effects | DSST score difference | 1.0 score on a scale | Standard Deviation 7.8 |
| Envarsus | Change in Neurocognitive Side Effects | MOCA score difference | 0.2 score on a scale | Standard Deviation 2.9 |
| Envarsus | Change in Neurocognitive Side Effects | DSST score difference | 1.26 score on a scale | Standard Deviation 7.5 |
Secondary
Change in Self-reported Side Effects
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.
Time frame: 6 weeks after randomization and baseline testing
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Immediate Release Tacrolimus | Change in Self-reported Side Effects | -1.2 score on a scale | Standard Deviation 7.5 |
| Envarsus | Change in Self-reported Side Effects | -3.1 score on a scale | Standard Deviation 9 |
Secondary
Kidney Graft Survival
Number of kidney grafts still functioning at the end of the study
Time frame: 6 months after transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immediate Release Tacrolimus | Kidney Graft Survival | 32 kidney grafts |
| Envarsus | Kidney Graft Survival | 32 kidney grafts |
Secondary
Patient Survival
Number patients who survived during the study
Time frame: 6 months after transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Immediate Release Tacrolimus | Patient Survival | 32 Participants |
| Envarsus | Patient Survival | 32 Participants |