Opioids in Chronic Kidney Disease Patients Undergoing Hemodialysis (OCKD)

Clinical Trial Simulation Using ODE/PDE Hemodialysis Model for Quantifying Oxycodone's Removal in End-Stage Kidney Disease

To measure oxycodone's intradialytic mass transfer rate coefficient and oxycodone's removal rate using an ODE/PDE hemodialysis model. To implement a rational clinical strategy for estimating a patient's post-hemodialysis oxycodone restoration dose using results from an ODE/PDE model of hemodialysis.

Study Overview

Status

Unknown

Intervention / Treatment

Detailed Description

Clinical Trial Simulation Design and Investigational Plan: Our study sample will consist of a group of 10 randomly selected virtual Caucasian hemodialysis patients with Stage 5 chronic kidney disease (CKD) and a group of 10 randomly selected Caucasian age and weight matched healthy controls. Patients, 5 women and 5 men in each group, will be synthesized using clinical trial simulation techniques from the case report data reported by Lee, Leng, and Cooper and the experiments by Kirvela and coworkers. Our goal is to learn about the populations from which the study samples are drawn. To meet this goal, the investigators will perform Monte Carlo simulation.

Both virtual control subjects and experimental hemodialysis patients meeting all inclusion/exclusion criteria will be studied in two phases.

In phase 1, subjects will receive a ceiling dose of controlled-release oxycodone hydrochloride (hereafter CR-OC) totaling 40 mg twice daily for 2 weeks prior to the experimental hemodialysis procedure on day 15. Because patients in the hemodialysis group will be anuric, they will undergo hemodialysis three times weekly.10 During that time, they will receive supplemental oral immediate-release oxycodone every 4 h as needed to control their pain up to a visual analog scale level of < 3. These pain levels would correspond with plasma oxycodone concentrations of 20-50 ng/mL.

Patients will be instructed to take their last dose of CR-OC 2 to 3 hours before starting the experimental hemodialysis procedure. This dosing schedule will ensure that the time to CR-OC's maximum concentration (Tmax) and its maximum concentration (Cmax) will be reached at the time of blood sampling at t = 0, enabling accurate assessment of CR-OC's elimination with negligible influence from absorption or redistribution.

At 8:00 am on the 15th day, and this is phase 2 of the study, each individual will undergo hemodialysis for 4 hours. Two independent simultaneous blood samples for measurement of plasma oxycodone concentrations from both arterial inflow (Cin) and venous outflow (Cout) sites will be obtained immediately upon starting hemodialysis (t = 0) and immediately after hemodialysis before shutting off the machine (t = 4). For all calculations and ODE/PDE modeling (see Model Diagram), the oxycodone concentrations from those samples will be combined and averaged. Oxycodone's intradialytic extraction ratio will be calculated from the simultaneously sampled arterial (inflow) and venous (outflow) plasma oxycodone concentrations by dividing their difference by the arterial plasma oxycodone concentrations.

Controls will eat three light meals and a bedtime snack daily. Hemodialysis patients will eat a standard renal diet. Foods will be free of known inhibitors of CYP2D6. Individuals will be digitally abstained from nicotine, caffeine, grapefruit juice and alcohol during the course of the study.

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • Michigan
      • Dearborn, Michigan, United States, 48124
        • Recruiting
        • Oscar A. Linares, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Healthy, non-smoking, opioid intolerant Caucasian men and women controls.
  • Hemodialysis patients age 44 ± 10 (mean ± SD) years and normal controls 36 ± 9 years.
  • No statistically significant difference in weight between hemodialysis and control patients.
  • Mean serum creatinine concentrations of 7.29 ± 1.48 mg/dL in hemodialysis patients and 0.81 ± 0.12 mg/dL in controls (normal 0.7 to 1.3 mg/dL for men and 0.6 to 1.1 mg/dL for women)
  • Mean urine output of 1.83 ± 0.47 mL/hr (44 ± 11 mL/24 hr) in hemodialysis patients and 62.32 ± 16.01 mL/hr (1496 ± 384 mL/24 hr) in controls.
  • Patients in both groups with normal liver function. Serum prothrombin time (PT/INR), aPTT, albumin, bilirubin (direct and indirect), liver transaminases, gamma-glutamyl transferase and alkaline phosphatase normal.

Exclusion Criteria:

  • In both groups, a clinically significant electrocardiogram (ECG) abnormality.
  • An uncontrolled clinically significant cardiovascular condition other than end-stage kidney disease.
  • Elevated transaminases, alkaline phosphatase, bilirubin, low phosphodiesterase, elevated ammonia levels, low glucose, elevated lactate, elevated creatinine, and hypoxia (hepatorenal syndrome)
  • Serum positive for HIV, hepatitis BsAg, or Hepatitis C
  • A history of drug or alcohol abuse within the past 24 months
  • Currently participating (or participated within the previous 30 days in an investigational therapeutic or device study
  • Female who is pregnant, nursing, or of child-bearing potential not practicing effective contraceptive methods.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: control
Oxycodone will be administered and subjects will undergo hemodialysis
Controlled release oxycodone 40 mg twice daily
Other Names:
  • OxyContin
Experimental: hemodialysis
Oxycodone will be administered and subjects will undergo hemodialysis
Controlled release oxycodone 40 mg twice daily
Other Names:
  • OxyContin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Oxycodone's intradialytic mass transfer coefficient
Time Frame: t=0 to t=4 hours
t=0 to t=4 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Oscar A Linares, MD, Emerio & Lourdes Linares Research and Education Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2015

Primary Completion (Anticipated)

September 1, 2015

Study Completion (Anticipated)

December 1, 2015

Study Registration Dates

First Submitted

May 20, 2015

First Submitted That Met QC Criteria

May 21, 2015

First Posted (Estimate)

May 22, 2015

Study Record Updates

Last Update Posted (Estimate)

May 22, 2015

Last Update Submitted That Met QC Criteria

May 21, 2015

Last Verified

May 1, 2015

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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