Alterations in Cognitive Function and Cerebral Blood Flow After Conversion From Immediate Release Tacrolimus to Slow Release Envarsus

The purpose of this study is to learn if conversion from immediate release tacrolimus to Envarsus improves cerebral blood flow, brain blood flow response to exercise, and cognition.

Study Overview

• Status: Completed
• Conditions: End Stage Renal Disease
• Intervention / Treatment: Drug: Tacrolimus; Drug: Envarsus

Detailed Description

Each patient will have two study assessments: one at baseline and another one at 12 weeks after the baseline assessment. Each assessment may be divided into 2 visits to accommodate the MRI and TCD (Transcranial Doppler ultrasound). Detailed medical history will be extracted from the patients' medical records, interviews and questionnaires. We will obtain brain MRI (without gadolinium contrast) in enrolled patients. Neuropsychological test (NP) tests will include a standard battery to detect subclinical changes in cognition which can be missed by screening tests like the mini mental state exam.

• Study Type: Observational
• Enrollment (Actual): 30

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients will be recruited from the KUMC kidney transplant clinic. Both male and female kidney transplant recipients aged 18 to 85 will be included.

Description

Inclusion Criteria:

• age between 18 and 85 years
• English speaking (NP tests will be in English);
• able to sign informed consent
• able to arrange transportation to and from study sites
• without acute stroke, concussion or traumatic brain injury
• received a kidney transplant at least 12 weeks before recruitment
• stable kidney function with serum creatinine <3mg/dl

Exclusion Criteria:

• are claustrophobic or have other contra-indication for MRI
• have hearing or visual impairment
• are unable to read, write, speak or understand English
• have uncontrolled psychosis or seizure disorder or are currently using antipsychotics or anti-epileptics
• dual organ transplant
• oxygen-dependent chronic obstructive pulmonary disease
• diagnosis of dementia
• unable to perform exercise on the Nustep (muscle weakness or cardiac safety concern)
• uncontrolled blood pressure

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Study Arm; The patients in the study arm will be converted from immediate release Tacrolimus to Envarsus. After obtaining informed consent, participants will undergo baseline tests for cognitive function and cerebral blood flow. After 12 weeks, cognition and brain blood flow will be assesses again in all enrolled patients.	Drug: Envarsus; Patients will then be randomized in the ratio of 2:1 with 20 being in the study arm and 10 in the control arm. Envarsus will be prescribed by the transplant team per conversion guidelines. The transplant team will monitor drug levels, per the dosing guidelines.
Control Arm; Patients in the control arm will remain on the immediate release Tacrolimus. After obtaining informed consent, participants will undergo baseline tests for cognitive function and cerebral blood flow. After 12 weeks, cognition and brain blood flow will be assesses again in all enrolled patients.	Drug: Tacrolimus; The patient's physician will prescribe drug according to standard practice.; Other Names: Prograf

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cognitive function using a battery of neuropsychological tests	Battery aggregate scores include such tests as: Mini Mental Sate Exam, Montreal Cognitive Assessment, Digit Span, Logical Memory, Category Fluency, Trail Making, Digit Symbol, Block Design, Stroop, Buschke Free and Cued Reminding Test.	Change from Baseline to Week 12
Change in cerebral blood flow	including brain blood flow response curve to exercise or cerebral reactivity	Change from Baseline to Week 12

Collaborators and Investigators

• Sponsor: University of Kansas Medical Center
• Collaborators: Veloxis Pharmaceuticals
• Investigators: Principal Investigator: Aditi Gupta, MD, University of Kansas Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2018
• Primary Completion (Actual): March 3, 2021
• Study Completion (Actual): March 3, 2021

Study Registration Dates

• First Submitted: September 13, 2018
• First Submitted That Met QC Criteria: October 9, 2018
• First Posted (Actual): October 11, 2018

Study Record Updates

• Last Update Posted (Actual): April 27, 2021
• Last Update Submitted That Met QC Criteria: April 26, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: End Stage Renal Disease
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Diseases; Kidney Failure, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: STUDY00142282

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No