A Pilot Study to Evaluate Impact on Neurological Side Effects (Cognition, Memory, and Tremor) in Elderly (Age>65) Patients

Previous studies have shown that elderly patients experience higher trough levels of tacrolimus and are more sensitive to the effects of medications, they experience higher occurrence and severity of such medication related toxicities. Therefore, the investigators hypothesize that by transitioning patients from tacrolimus immediate release to Envarsus ®, the peak-dose effect will be eliminated or attenuated, leading to a significant decrease in neurocognitive toxicities in the older patient population.

Study Overview

• Status: Completed
• Conditions: Toxicity; Neurotoxicity; Kidney Transplant; Complications; Drug Toxicity
• Intervention / Treatment: Drug: IR Tacrolimus; Drug: Envarsus

Detailed Description

The investigators will conduct a single-center, prospective, open-label, randomized study to evaluate the difference in neurocognitive side effects between Envarsus and immediate release tacrolimus. Eligible patients will be enrolled within 8 weeks post-transplantation. They will be administered a baseline panel of neurocognitive tests. They will then be randomized to either continue on immediate release tacrolimus or Envarsus. 6 weeks after randomization, the neurocognitive tests will be repeated.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ling-Xin Chen, MD; Phone Number: 916.734.5141; Email: lxchen@ucdavis.edu

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • UC Davis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Recipient of a kidney transplant
2. Age 60 or greater at the time of transplant
3. Kidney graft is functional (not dialysis dependent) by 4 weeks post-transplant
4. Have IR tacrolimus as maintenance therapy
5. Have BMI < 35 at time of transplant
6. Achieve therapeutic tacrolimus level within 4 weeks post-transplant

Exclusion Criteria:

1. Recipient of a simultaneous non-kidney transplant (pancreas)
2. Had an episode of rejection before study enrollment
3. Had a TIA/CVA after transplantation and before study enrollment
4. Had a neurologic injury after transplantation and before study enrollment
5. Blindness
6. Have an mTOR inhibitor as maintenance therapy
7. Nonadherence, as determined by a trough level less than 7 ng/mL after achieving therapeutic level with no other rationale for sub-therapeutic levels.
8. Adults unable to consent
9. Pregnant women
10. Prisoners

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Immediate Release Tacrolimus; Patients will receive immediate release tacrolimus	Drug: IR Tacrolimus; Patients will be randomized to receiving IR Tacrolimus instead of Envarsus
Experimental: Envarsus; Patients will be converted to Envarsus formulation of tacrolimus	Drug: Envarsus; Patients will be randomized to receiving Envarsus instead of IR Tacrolimus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in neurocognitive side effects	6 weeks after randomization and baseline testing

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in self-reported side effects	6 weeks after randomization and baseline testing
Tacrolimus dose over concentration ratio	6 weeks after randomization and baseline testing
Kidney graft survival	6 months after transplant
Patient survival	6 months after transplant

Collaborators and Investigators

• Sponsor: University of California, Davis
• Collaborators: Veloxis Pharmaceuticals
• Investigators: Principal Investigator: Ling-Xin Chen, MD, UC Davis

Publications and helpful links

Helpful Links

• Learn more or sign up for the study here!

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2018
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): July 31, 2023

Study Registration Dates

• First Submitted: March 5, 2018
• First Submitted That Met QC Criteria: March 5, 2018
• First Posted (Actual): March 12, 2018

Study Record Updates

• Last Update Posted (Estimated): December 5, 2023
• Last Update Submitted That Met QC Criteria: December 1, 2023
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Elderly; Tacrolimus; Neurotoxicity; Calcineurin inhibitors
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Nervous System Diseases; Poisoning; Drug-Related Side Effects and Adverse Reactions; Neurotoxicity Syndromes; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: 1044220

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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