Neurocognitive Function Changes With Extended-Release Tacrolimus Among Older Kidney Transplant Recipients

Phase 4

Not yet recruiting

• Conditions: Kidney Transplant Recipients; Old Age
• Interventions: Drug: Conversion to extended-release tacrolimus; Drug: Maintenance of immediate-release tacrolimus

• Registration Number: NCT06751992
• Lead Sponsor: Massachusetts General Hospital

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).

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-11
• Study First Submitted: 2024-12-13
• Study First Submitted QC: 2024-12-20
• Study First Posted: 2024-12-30
• Study Start: 2025-05-01
• Last Update Submitted: 2025-05-06
• Last Update Posted: 2025-05-09
• Primary Completion: 2027-05-01
• Study Completion: 2027-10-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 92

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
• Deafness
• Intellectual disabilities
• Pregnancy
• eGFR <15 mL/min/1.73 m2 at the time of enrollment
• Total bilirubin >3.0 mg/dL

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Envarsus XR conversion	Conversion to extended-release tacrolimus	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.
Prograf maintenance	Maintenance of immediate-release tacrolimus	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.

Primary Outcome Measures

Name	Time	Method
The difference in changes of neurocognitive function in intermediate-term (Total cognition composite, standard score)	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)	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)	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)	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)	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)	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 Outcome Measures

Name	Time	Method
The difference in changes of neurocognitive function in short-term (Total cognition composite, standard score)	3 month	Same as described above
The difference in changes of neurocognitive function in short-term (Fluid composite, standard score)	3 month	Same as described above
The difference in changes of neurocognitive function in short-term (Crystallized composite, standard score)	3 month	Same as described above
The difference in changes of neurocognitive function in short-term (Total cognition composite, T score)	3 month	Same as described above
The difference in changes of neurocognitive function in short-term (Fluid composite, T score)	3 month	Same as described above
The difference in changes of neurocognitive function in short-term (Crystallized composite, T score)	3 month	Same as described above
The changes in quality of life, measured by SONG-LP questionnaire	3 month and 12 month	The Standardized Outcome in Nephrology-Life Participation (SONG-LP) questionnaire will evaluate each participant's engagement in significant life domains in correlation with the intervention. This questionnaire assesses life participation in the areas of leisure, family, work, and social activities through four simple questions. The score ranges from 4 to 20, with a higher score indicating greater engagement in life activities. The difference in changes of total score from baseline between the two intervention groups will be obtained.
The changes in tremor, measured by QUEST questionnaire	3 month and 12 month	Quality of Life in Essential Tremor (QUEST) questionnaire will be used to assess tremors subjectively. This questionnaire comprises 30 items contributing to the five dimensions: physical/activities of daily living, psychosocial, communication, hobbies/leisure, and work/finances. The investigators will also obtain self-rated tremor severity in various body parts. The score ranges from 0 to 120, with a higher score indicating a greater impact on their QOL from tremor. The investigators will compare the changes in total score and the score on each scale from baseline between the two intervention groups.
The changes in sleep quantity, measured by a wearable device	3 month and 12 month	The investigators will assess each participant's sleep quantity using wearable devices. The participants will be instructed to wear the device continuously for 14 days at pre-specified time points during the study period. Sleep quantity will be represented by the total amount of time spent asleep. The difference in changes in sleep quantity from baseline will be compared between the two intervention groups.
The changes in sleep quality, measured by a wearable device	3 month and 12 month	The investigators will objectively assess each participant's sleep quality using wearable devices. The participants will be instructed to wear the device continuously for 14 days at pre-specified time points during the study period. Sleep quality will be measured as a percentage of time spent in deep sleep and REM sleep to the total sleep time. A higher percentage indicates a better sleep quality. The changes in sleep quality from baseline will be compared between the two intervention groups.

Trial Locations

Locations (1)

MGH Kidney Transplant Clinic; 🇺🇸 Boston, Massachusetts, United States