Comparison of the Cognitive and Motor Effects of Treatment Between an Immediate- and Extended-release Tacrolimus (Envarsus® XR) Based Immunosuppression Regimen in Kidney Transplant Recipients

Phase 1

Completed

• Conditions: Kidney Transplant Failure and Rejection
• Interventions: Drug: extended release tacrolimus; Drug: immediate-release tacrolimus

• Registration Number: NCT03437577
• Lead Sponsor: University of Minnesota

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.

Study Timeline

• Study First Submitted: 2018-02-12
• Study First Submitted QC: 2018-02-12
• Study First Posted: 2018-02-19
• Study Start: 2018-05-08
• Primary Completion: 2020-03-31
• Study Completion: 2020-03-31
• Results First Submitted: 2021-02-25
• Status Verified: 2021-03
• Results First Submitted QC: 2021-03-22
• Last Update Submitted: 2021-03-22
• Results First Posted: 2021-04-15
• Last Update Posted: 2021-04-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
extended release tacrolimus	extended release tacrolimus	replace standard of care
immediate-release tacrolimus	immediate-release tacrolimus	This is standard of care

Primary Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States