Neurocognitive Function Changes With Once-Daily Extended-Release Tacrolimus (Envarsus XR) Conversion Compared to Twice-Daily Immediate Release Tacrolimus Maintenance Among Older Kidney Transplant Recipients
Overview
- Phase
- Phase 4
- Intervention
- Conversion to extended-release tacrolimus
- Conditions
- Kidney Transplant Recipients
- Sponsor
- Massachusetts General Hospital
- Enrollment
- 92
- Locations
- 1
- Primary Endpoint
- The difference in changes of neurocognitive function in intermediate-term (Total cognition composite, standard score)
- Status
- Not yet recruiting
- Last Updated
- 5 months ago
Overview
Brief Summary
The objective of this randomized controlled study is to assess the neurocognitive outcomes between individuals using immediate-release (IR) tacrolimus (Prograf®) and those who were converted to extended-release tacrolimus (Envarsus XR) among older kidney transplant recipients (KTRs).
Investigators
Leonardo V. Riella, MD, PhD
Medical Director of Kidney Transplantation
Massachusetts General Hospital
Eligibility Criteria
Inclusion Criteria
- •Able to give informed consent for participation in the study
- •Patients who have regular outpatient follow-up at the Massachusetts General Hospital (MGH) transplant center
- •≥1 year since the latest kidney transplantation
- •On IR tacrolimus as maintenance therapy
- •At a stable therapeutic tacrolimus level (5-10 ng/ml) over the last ≥3 months
- •Stable kidney function \[\<20% variability between the last two estimated glomerular filtration rate (eGFR)\]
- •Utilizing English or Spanish as the primary language
Exclusion Criteria
- •Dual organ transplantation
- •Rejection within the last three months
- •History of moderate to severe dementia (defined by Dementia Severity Rating Scale ≥19)
- •History of Parkinson's disease
- •Decompensated liver disease
- •Active cancer
- •Uncontrolled depression or anxiety
- •Blindness
- •Intellectual disabilities
- •Pregnancy
Arms & Interventions
Envarsus XR conversion
Patients who are randomized to this group will receive extended-release tacrolimus (Envarsus XR) at 80 percent of their total daily dose of IR tacrolimus (Prograf) before the switch. Tacrolimus trough level will be obtained 3-4 weeks after the conversion to ensure appropriate dosage.
Intervention: Conversion to extended-release tacrolimus
Prograf maintenance
Patients in the IR tacrolimus (Prograf) maintenance group will continue with their current dose of IR tacrolimus (Prograf) before enrollment unless the drug trough levels deviate from the therapeutic range.
Intervention: Maintenance of immediate-release tacrolimus
Outcomes
Primary Outcomes
The difference in changes of neurocognitive function in intermediate-term (Total cognition composite, standard score)
Time Frame: 12 month
Neurocognitive functions will be assessed across multiple cognitive domains using the NIH toolbox-Cognitive battery (NIHTB-CB) version 3. The NIHTB-CB version 3 encompasses seven tests to assess attention, executive function, language, memory, and processing speed. The total cognition composite will be derived by averaging normalized scores. The results will be reported in Standard Scores \[SS; mean of 100, standard deviation (SD) of 15\] adjusting the age of the subject. The investigators will compare the changes in standard score from baseline between the two intervention groups.
The difference in changes of neurocognitive function in intermediate-term (Fluid composite, standard score)
Time Frame: 12 month
The fluid composite score will be obtained using the NIH toolbox-Cognitive battery (NIHTB-CB) version 3, similarly as described above. The fluid cognition composite will be derived by averaging normalized scores. The results will be reported in Standard Scores \[SS; mean of 100, standard deviation (SD) of 15\] adjusting the age of the subject. The investigators will compare the changes in standard score from baseline between the two intervention groups.
The difference in changes of neurocognitive function in intermediate-term (Crystallized composite, standard score)
Time Frame: 12 month
The crystallized composite score will be obtained using the NIH toolbox-Cognitive battery (NIHTB-CB) version 3, similarly as described above. The crystallized cognition composite will be derived by averaging normalized scores. The results will be reported in Standard Scores \[SS; mean of 100, standard deviation (SD) of 15\] adjusting the age of the subject. The investigators will compare the changes in standard score from baseline between the two intervention groups.
The difference in changes of neurocognitive function in intermediate-term (Total cognition composite, T score)
Time Frame: 12 month
The total composite score will be obtained using the NIH toolbox-Cognitive battery (NIHTB-CB) version 3, similarly as described above. The total cognition composite will be derived by averaging normalized scores. The results will be reported in T scores (mean of 50 and SD of 10) with adjustments for age, gender, education, and race/ethnicity. The investigators will compare the changes in T score from baseline between the two intervention groups.
The difference in changes of neurocognitive function in intermediate-term (Fluid composite, T score)
Time Frame: 12 month
The fluid composite score will be obtained using the NIH toolbox-Cognitive battery (NIHTB-CB) version 3, similarly as described above. The fluid cognition composite will be derived by averaging normalized scores. The results will be reported in T scores (mean of 50 and SD of 10) with adjustments for age, gender, education, and race/ethnicity. The investigators will compare the changes in T score from baseline between the two intervention groups.
The difference in changes of neurocognitive function in intermediate-term (Crystallized composite, T score)
Time Frame: 12 month
The crystallized composite score will be obtained using the NIH toolbox-Cognitive battery (NIHTB-CB) version 3, similarly as described above. The crystallized cognition composite will be derived by averaging normalized scores. The results will be reported in T scores (mean of 50 and SD of 10) with adjustments for age, gender, education, and race/ethnicity. The investigators will compare the changes in T score from baseline between the two intervention groups.
Secondary Outcomes
- The difference in changes of neurocognitive function in short-term (Total cognition composite, standard score)(3 month)
- The difference in changes of neurocognitive function in short-term (Fluid composite, standard score)(3 month)
- The difference in changes of neurocognitive function in short-term (Crystallized composite, standard score)(3 month)
- The difference in changes of neurocognitive function in short-term (Total cognition composite, T score)(3 month)
- The difference in changes of neurocognitive function in short-term (Fluid composite, T score)(3 month)
- The difference in changes of neurocognitive function in short-term (Crystallized composite, T score)(3 month)
- The changes in quality of life, measured by SONG-LP questionnaire(3 month and 12 month)
- The changes in tremor, measured by QUEST questionnaire(3 month and 12 month)
- The changes in sleep quantity, measured by a wearable device(3 month and 12 month)
- The changes in sleep quality, measured by a wearable device(3 month and 12 month)