Kidney Transplant Failure and Rejection
Conditions
Keywords
Kidney, Transplant
Brief summary
The primary objective is to compare the effect of treatment with an immediate-release tacrolimus to an extended-release tacrolimus (i.e., Envarsus® XR) immunosuppressive regimen on cognitive and motor function in kidney transplant recipients
Detailed description
Between four (4) months and 14 months after receiving a kidney transplant and, per standard of care (SOC), having been placed on an immediate-release (IR) tacrolimus immunosuppressant regimen, participants in this study will undergo cognitive and motor function testing and have a blood sample collected (BASELINE). Half of the participants will then be randomly converted to extended-release (XR) tacrolimus (Envarsus® XR) while the other half will remain on IR tacrolimus for the duration of the study. Both the IR and XR groups will repeat the cognitive and motor function testing and have a blood sample collected at 6, 12, and 24 weeks Post-BASELINE. A practice version of the cognitive and motor function tests will be administered no more than 60 days prior to the baseline visit (Pre-BASELINE). Alternate versions of the cognitive and motor tests will be used at each Post-BASELINE testing session to control for possible practice effects. The primary objective is to compare the effect of treatment with an immediate-release tacrolimus to an extended-release tacrolimus (i.e., Envarsus® XR) immunosuppressive regimen on cognitive and motor function in kidney transplant recipients. The secondary objective is to determine the factors that explain inter-individual variability in cognitive response. Pharmacokinetic and demographic factors will be explored. Variability in cognitive response between individuals can be large. A population approach (nonlinear, mixed effects) will be used. Measurement of drug concentration will be the dependent variable.
Interventions
Standard of care for transplant patients
Experimental care
Sponsors
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female kidney transplant recipient; 2. 18-65 years of age; 3. receiving a kidney transplant from a living or deceased donor; 4. if female, premenopausal and heterosexually active, must be using two forms of highly effective birth control (at least one of which must be a barrier method) which includes consistent and correct usage of established oral contraception, established intrauterine device or intrauterine system, or barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, starting at screening and throughout the study period and for 90 days after the final study drug administration; 5. written informed consent to participate in the study
Exclusion criteria
1. younger than 18 years of age; 2. older than 65 years of age; 3. Non-native level English speaker; 4. pregnant women 5. breastfeeding women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Controlled Oral Word Association Test (COWAT) | Change from baseline at 6,12, 24 weeks | During The Controlled Oral Word Association Test (COWAT), participants are asked to make verbal associations to different letters of the alphabet by saying all the words which they can think of beginning with a given letter. Three letters of progressively increasing associative difficulty are presented with 60 seconds allotted per letter for word retrieval. Scores are calculated as a sum of the total words produced across the 3 letter trials. The lowest possible score is zero, meaning no words could be produced. There is no limit to the higher end of the scale given that participants can produce as many words as possible for each of the three letters. Higher scores indicate greater word retrieval and better cognitive function. Outcome is reported as the change in COWAT between baseline and 6 weeks, baseline and 12 weeks, and baseline and 24 weeks. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Immediate-Release Tacrolimus This is standard of care
immediate-release tacrolimus: Standard of care for transplant patients | 3 |
| Extended-Release Tacrolimus replace standard of care
extended release tacrolimus: Experimental care | 5 |
| Non-Randomized Participants in this arm were not randomized to either arm. They ended study participation prior to randomization. | 10 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Post-Randomization | Physician Decision | 0 | 2 | 0 |
| Pre-Randomization | Withdrawal by Subject | 0 | 0 | 10 |
Baseline characteristics
| Characteristic | Extended-Release Tacrolimus | Non-Randomized | Total | Immediate-Release Tacrolimus |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 10 Participants | 18 Participants | 3 Participants |
| Age, Continuous | 60.4 years STANDARD_DEVIATION 1.9 | 49.2 years STANDARD_DEVIATION 10 | 52.8 years STANDARD_DEVIATION 9.7 | 52.3 years STANDARD_DEVIATION 9.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 8 Participants | 13 Participants | 2 Participants |
| Region of Enrollment United States | 5 participants | 10 participants | 18 participants | 3 participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 8 Participants | 2 Participants |
| Sex: Female, Male Male | 3 Participants | 6 Participants | 10 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 5 |
| other Total, other adverse events | 0 / 3 | 0 / 5 |
| serious Total, serious adverse events | 0 / 3 | 0 / 5 |
Outcome results
Primary
Change in Controlled Oral Word Association Test (COWAT)
During The Controlled Oral Word Association Test (COWAT), participants are asked to make verbal associations to different letters of the alphabet by saying all the words which they can think of beginning with a given letter. Three letters of progressively increasing associative difficulty are presented with 60 seconds allotted per letter for word retrieval. Scores are calculated as a sum of the total words produced across the 3 letter trials. The lowest possible score is zero, meaning no words could be produced. There is no limit to the higher end of the scale given that participants can produce as many words as possible for each of the three letters. Higher scores indicate greater word retrieval and better cognitive function. Outcome is reported as the change in COWAT between baseline and 6 weeks, baseline and 12 weeks, and baseline and 24 weeks.
Time frame: Change from baseline at 6,12, 24 weeks
Population: All participants who were randomized and participated in outcome measure data collection are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Immediate-Release Tacrolimus | Change in Controlled Oral Word Association Test (COWAT) | Baseline to 6 weeks | .44 score on a scale | Standard Deviation 0.51 |
| Immediate-Release Tacrolimus | Change in Controlled Oral Word Association Test (COWAT) | Baseline to 12 weeks | -0.88 score on a scale | Standard Deviation 1.89 |
| Immediate-Release Tacrolimus | Change in Controlled Oral Word Association Test (COWAT) | Basline to 24 weeks | 0.78 score on a scale | Standard Deviation 0.84 |
| Extended-Release Tacrolimus | Change in Controlled Oral Word Association Test (COWAT) | Baseline to 6 weeks | -2.11 score on a scale | Standard Deviation 2.83 |
| Extended-Release Tacrolimus | Change in Controlled Oral Word Association Test (COWAT) | Baseline to 12 weeks | -1.78 score on a scale | Standard Deviation 2.01 |
| Extended-Release Tacrolimus | Change in Controlled Oral Word Association Test (COWAT) | Basline to 24 weeks | -0.44 score on a scale | Standard Deviation 2.04 |